Protective role of tauroursodeoxycholate during harvesting and cold storage of human liver: a pilot study in transplant recipients. Transplantation 2001; 71: 1268.
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The emergence of cytomegalovirus resistance to ganciclovir therapy in kidney transplant recipients.
Transplant recipients that have not been previously exposed to the cytomegalovirus (CMV) are highly susceptible to viral diseases while under immunosuppression therapy. CMV disease requires prolonged therapy, facilitating the emergence of resistant strains. Persistence of positive antigenemia represents clinical evidence of the presence of resistant strains, although its frequency is unknown. These strains may present amino acid deletions or substitutions in conserved regions of the UL97 protein, point mutations in the DNA polymerase (UL54), or both. In this study we aimed to analyze the prevalence of mutations associated with ganciclovir resistance in transplant recipients. Fifteen kidney transplant recipients and four kidney-pancreas transplant recipients, with a positive and oscillating CMV viremia detected by sequential antigenemia test, were enrolled. The UL97 gene was amplified by Nested-PCR and enzymatically digested in samples of these patients in order to detect mutations in the most common codons, such as 460 (M460V), 594 (A594V) and 595(L595S/F). The end-product fragments were further sequenced. Nine (47.4%) out of 19 patients presented with mutations in UL97 at codons L595S (55.6%), A594V (11.1%), A595F/A594V (11.1%) and L595S/A594V (22.2%). None presented with mutation at the M460V codon. Renal transplant patients with oscillation in viral load for more than 2 weeks might have developed viral resistance to anti-drug therapy. Its detection might aid physicians in their clinical plan of tapering the patient's immunosuppression.
Adolescent↗
Increasing medication access to transplant recipients.
Transplant recipients require numerous medications to maintain graft survival and health. Post-transplant medication therapy costs greater than 12000 dollars annually, and the cost of therapy is expected to increase. Although medication costs continue to rise, a substantial portion of Americans lack adequate health insurance or do not have any insurance coverage. To facilitate health, it is imperative that health care providers are familiar with programs that are available to increase prescribed medication access to transplant recipients. The purpose of this manuscript is to provide an overview of common programs available to increase transplant recipients' access to medications. In addition to discussing the consequences of medication non-compliance, this manuscript reviews Medicare, Medigap, Medicaid, Qualified Medicare Beneficiaries, and pharmaceutical manufacturers' medication assistance programs and its use to increase medication access to solid-organ transplant recipients.
Drug Prescriptions↗
Low incidence of c-Ha-ras gene mutations in benign and malignant cutaneous lesions from transplant recipients.
Transplant recipients successively develop benign, premalignant and malignant skin lesions on sun-exposed areas. It has been suggested that UV radiations might induce mutations in ras oncogenes and p53 tumour-suppressor gene, responsible for skin cancers. With PCR and oligoprobe hybridization, we investigated c-Ha-ras gene mutations at codons 12 and 61 in 120 cutaneous lesions from grafted patients, since they could represent a marker of the evolution of benign skin lesions towards malignancy in this population; 29 similar skin biopsies from non-immunosuppressed patients were also analyzed. In transplant recipients, we detected mutations at codon 12 only in 1/42 non-melanoma skin cancers and 2/29 pre-cancerous keratoses. No mutation was detected in 11 cases of cutaneous Bowen's disease from grafted patients and in pre-malignant and malignant skin samples from control patients. Benign warts exhibited an overall incidence of 18% and 15% of mutations at codon 12 of c-Ha-ras gene in grafted and control patients respectively. We detected only one mutation at codon 61 in a plantar wart. Human papillomaviruses (HPV) are thought to be involved in the malignant evolution of cutaneous disorders in transplant recipients and cooperate with a ras oncogene to induce malignancy in vitro. The presence of HPV DNA in our series of skin samples from grafted patients showed no correlation with the occurrence of c-Ha-ras mutations. Our findings indicate that c-Ha-ras-gene activation by mutations is rare in cutaneous lesions from transplant recipients, and is unlikely to play a crucial role in transformation towards malignancy in skin carcinogenesis among grafted patients.
Animals↗
Vaccination, screening for malignancy, and health maintenance of the liver transplant recipient.
Transplant recipients are highly motivated to maintain their recovered health status and are generally compliant with pharmacotherapy and medical follow-up. As well as routine blood tests and monitoring of immunosuppressant drug levels, recipients require immunization updates and regular screening for malignancy, diabetes, hypertension, hyperlipidemia, and ophthalmologic complications. Little information is available about the consistent implementation of these health maintenance strategies in this population. A telephone survey of liver transplant recipients was conducted using a 20-item questionnaire. It was designed to assess the frequency and adequacy of health maintenance screening, immunizations, and screening tests for malignancy, which are specific to the liver transplant population. We contacted 60 liver recipients transplanted at our institution between 1992 and 1996. The mean age of the patients (31 men and 29 women) was 48 years (range, 42-56 years). Before transplantation, pneumococcal and hepatitis B vaccination occurred in 13% and 18%, respectively. After transplantation, 27% had received pneumococcal vaccination and none had received primary vaccination for hepatitis B. Forty-eight percent received yearly influenza vaccination. Of 60 questioned recipients, 2 were aware of their varicella exposure status or a possible need for varicella immunoglobulin if a primary exposure to chickenpox were to occur. Two were aware of the need for the recipient's children or grandchildren who were undergoing polio vaccination to receive an inactivated intramuscular polio preparation. Yearly screening for dermatologic or oral malignancies was provided to only 40% of patients. Physician-performed breast examination or screening mammograms was done in 38% of the surveyed women. Eleven percent of the women had received a gynecologic examination with a cervical cytologic examination within the prior 2 years. Of the male recipients, 68% received either digital prostate examination or serum prostate specific antigen determinations or both. Of 60 recipients, 30 had had either flexible sigmoidoscopy or colonoscopy within the previous 2 years. Yearly dental examinations were performed on 75% of patients, and more than 90% had at least yearly blood pressure and weight determinations. Of 60 patients, 41 were aware of cholesterol and lipid profiles having been performed within the past 2 years. Ophthalmologic screening was performed in 83% of surveyed recipients. This survey suggests that routine health maintenance management is less than optimal in this population. Follow-up based on a standard protocol may improve the health care of these patients.
Adult↗
Enzymatic variability of Candida krusei isolates in a course of fungal infection in a liver transplant recipient.
Transplant recipients are at high risk of fungal infections. The main site of fungal infections in patients undergoing liver transplantation is the abdominal cavity. One factor determining the pathogenicity of fungi is their ability to secrete hydrolytic enzymes. The aim of this study was to assess the enzymatic activity of Candida krusei, which caused an infection in a liver transplant recipient. The clinical specimens included swabs of throat, nose, and two drains, as well as bile, stool, and abdominal cavity aspirate. The yeast-like fungi isolated were identified by an ID 32 C test (bioMérieux) and their enzymatic activity assayed with the use of an API-ZYM test. Two biotypes of C. krusei were identified, depending on the source of the clinical specimen. The C. krusei isolates cultured from a throat swab, a nasal swab, and one of the drains secreted esterase lipase C8 (enzyme IV) and valine arylamidase (enzyme VII), in contrast to those isolated from the bile, abdominal cavity fluid, another drain, and stool. Characterization of two biotypes of C. krusei isolates cultured from different clinical samples from several infection sites indicated an ability of C. krusei to adapt to variable environmental conditions.
Candida↗
[Human papillomaviruses and cellular oncogenes (c-myc, c-Ha-ras) in cutaneous and mucosal lesions in transplantation recipients].
Transplant recipients develop numerous benign and malignant cutaneous and mucosal lesions in which histological signs of human papillomavirus (HPV) infection are observed. To investigate the role of HPV and c-myc and c-Ha-ras cellular oncogenes' activation in transplanted patients lesions, we used in situ hybridization with biotinylated probes and Southern blot to detect HPV and oncogenes DNA. We analyzed 36 lesions from grafted patients: 11 common warts, 10 actinic keratoses, 13 squamous cell carcinomas and 2 anogenital papillomas. With in situ hybridization, HPV DNA was detected in 14/36 lesions, 10 of which contained several HPV types. Benign and potentially oncogenic HPV types were detected in warts as well as in squamous cell carcinomas. The Southern blot technique confirmed the distribution of HPV types. Group specific viral antigen was detected in 12 lesions, mainly warts. C-Ha-ras oncogene was amplified in 13 lesions and c-myc oncogene in 10 lesions, 9 of which showed both oncogene amplification. The results obtained with in situ hybridization for c-myc gene amplification were confirmed with the Southern blot technique in 11/14 cases. Ras and/or myc amplification was more frequent in squamous cell carcinomas and anogenital papillomas than in warts and actinic keratoses. The amplification was not always linked to the presence of HPV DNA; however, it was more frequent in lesions infected by potentially oncogenic HPV types than in lesions containing only benign HPV types. Myc and p21 oncoproteins were respectively localized in the nucleus and on the membrane of epithelial cells by immunofluorescence. Most lesions showed a good concordance between the detection of oncogene DNA and proteins. Our results suggest than c-Ha-ras and c-myc cellular oncogenes' activation and HPV infection could play a role in the cancerization of cutaneous lesions from transplant recipients.
Genes, myc↗
Clinically-based determination of safe DNAemia cutoff levels for preemptive therapy or human cytomegalovirus infections in solid organ and hematopoietic stem cell transplant recipients.
Transplantation Centers using human cytomegalovirus (HCMV) antigenemia-based preemptive therapy will need to replace in the near future the antigenemia assay with a more standardized and automatable assay, such as a molecular assay quantifying HCMV DNA in blood (DNAemia). Thus, in view of replacing antigenemia with clinically safe cutoff values, DNAemia levels corresponding to antigenemia cutoffs guiding HCMV preemptive therapy were determined retrospectively in solid organ and hematopoietic stem cell transplant recipients (HSCTR) using an "in-house" quantitative PCR (QPCR) method. Since preemptive therapy had prevented appearance of HCMV disease in all patients tested, DNA cutoffs determined retrospectively had to be considered as safe clinically as antigenemia cutoffs used prospectively. However, in solid organ transplant recipients (SOTR), initiating preemptive therapy upon an antigenemia cutoff of 100 pp65-positive leukocytes, a DNAemia cutoff of 300,000 copies/ml blood had positive and negative predictive values of >90%, indicating that a DNAemia cutoff could achieve, in terms of prevention of HCMV disease, the same clinical results as the antigenemia cutoff. In HSCTR, initiating preemptive therapy upon first antigenemia positivity, a DNAemia cutoff of 10,000 copies/ml blood had a positive predictive value of >90%, indicating that the great majority of patients treated under the antigenemia guidance would have been treated also using this DNA cutoff. On the other hand, the negative predictive value of 28.6% indicated that two out of three HSCTR had been treated under the antigenemia guidance having the same levels of viral DNA as the untreated patients. The data suggest that a quantitative cutoff could be adopted as a guiding criterion for preemptive therapy also in HSCTR. Regression analysis allowed to determine the DNAemia (corresponding to QPCR) cutoff values for two commercial assays tested both in solid organ and HSCTR. Retrospective DNAemia cutoff values will be verified for safety in prospective trials.
Antigens, Viral↗
Isoniazid does not affect bioavailability of cyclosporine in renal transplant recipients.
Transplant recipients are predisposed to develop opportunistic infections such as tuberculosis, and isoniazid (INH) is used in most antitubercular therapeutic and prophylactic protocols. Cyclosporine (CyA) bioavailability increases with the concomitant use of drugs that inhibit hepatic cytochrome P-450 enzymes. There are conflicting reports on a possible interaction between the two drugs. Seven renal transplant recipients on CyA (Sandimmun Neoral) with slow acetylation status and also requiring concomitant INH prophylaxis (300 mg/day) against tuberculosis were studied. There were no significant changes in CyA pharmacokinetic parameters including CyA trough levels, total CyA exposure and CyA clearance before and 2 weeks after instituting INH prophylaxis. There was also no statistically significant correlation between INH levels and changes in CyA pharmacokinetic parameters before and after administration of INH. Even after all post-INH pharmacokinetic parameters were adjusted for INH levels, the differences in the above pre- and post-INH parameters did not reach statistical significance. Renal function during the study period remained constant and there were no episodes of CyA toxicity or acute rejection during and up to 4 weeks of INH treatment. We conclude that concomitant administration of INH and CyA is safe and is not associated with any appreciable alterations in the bioavailability of CyA.
Acetylation↗
Fungal skin infections in organ transplant recipients.
Transplantation is now currently and increasingly performed for the treatment of various acute and chronic diseases. Today the kidney, heart, lung, heart-lung, liver, pancreas, kidney-pancreas, small bowel and bone marrow are being transplanted. The immunological status of patients receiving such transplants exposes them to the risk of developing bacterial, viral and fungal infections. The etiological agents of mycotic diseases involving the skin of transplant recipients range from the common dermatophytes through yeasts such as Candida spp., Malassezia spp. and dimorphic fungi to the emerging molds Fusarium spp. and Pseudallescheria boydii. The very wide spectrum of fungi causing cutaneous disease produces equally varied clinical aspects. Lesions may be typical, but are very often aspecific or ambiguous. Cutaneous lesions may be the sign of a trivial mycotic disease or the marker of a disseminated, potentially lethal fungal illness, so great attention should be given to their early recognition. Cutaneous manifestations due to Candida spp., Aspergillus spp., dematiaceous fungi and Pityrosporum folliculitis are usually observed early after transplant, cryptococcosis more than 6 months later, while the frequency of dermatophytoses increases as time goes by. Coccidioides immitis, Histoplasma capsulatum and Blastomyces dermatitidis may appear any time after transplantation. The management of the more severe forms of cutaneous mycosis in transplant recipients is difficult. Besides the fact that early recognition is not easy, there are also problems regarding the effectiveness and the toxicity of the therapy and drug-drug interactions. Prophylactic measures to avoid fungal contamination must be performed during hospitalization; patients should be taught how to avoid contamination, not only during the first period after transplantation, when high dosage immunosuppressive drugs are given, but also later when a normal lifestyle is resumed.
Amphotericin B↗
Detection of mucosal human papillomavirus types 6/11 in cutaneous lesions from transplant recipients.
Transplant recipient develop multiple cutaneous lesions. We have identified human papillomavirus (HPV) DNA in these lesions using three different techniques, namely polymerase chain reaction (PCR), in situ hybridization, and Southern blotting. By PCR, HPV DNA was detected in 43 of 62 samples: warts, actinic keratoses, Bowen's disease, and squamous cell carcinomas. Surprisingly, HPV 6/11, usually associated with mucosa, were frequently found in benign, premalignant, and malignant cutaneous lesions (30/43 cases). Some of these biopsies were simultaneously tested by in situ hybridization and/or Southern blotting. By in situ hybridization, HPV 6/11 were identified in two warts and one squamous cell carcinoma among 29 tissue specimens tested. Of the three samples examined by Southern blotting, HPV 6/11 were detected in one squamous cell carcinoma. In patients from a control population cutaneous biopsies did not exhibit HPV types 6/11 except in Bowen's disease; HPV types 1 or 2 were mainly found in benign warts. These findings suggest that in transplant recipients, HPV can lose their specificity towards mucosa or cutaneous epithelium. The significance of the presence of HPV 6/11 in skin lesions remains unknown.
Base Sequence↗
Comparison of adenosine to dipyridamole in degree of coronary hyperemic response in heart transplant recipients.
Transplant coronary vasculopathy is associated with endothelial dysfunction. Microvascular function, assessed as coronary flow reserve, has been reported to be normal. We used intracoronary ultrasound technology to simultaneously assess conductance and resistance vessel function in response to standard dosages of the vasodilators adenosine and dipyridamole. Coronary hemodynamic changes were assessed in 11 heart transplant recipients, at a mean duration of 784 +/- 516 days after transplantation, using a 3.2Fr or 4.3Fr, 30-MHz ultrasound imaging catheter over a 0.014-inch Doppler guidewire. Measures of coronary average peak flow velocity (APV) and coronary cross-sectional area (CSA) were used to calculate volumetric flow during intravenous infusions of adenosine (140 micrograms/kg/min over 4 minutes) and dipyridamole (140 micrograms/kg/min over 4 minutes). Flow reserve was assessed as a ratio of maximal pharmacologically induced flow to steady baseline flow before infusion. Increase in APV (261.9% vs 194.6%, p = 0.005), lumenal CSA (+11.8% vs +4.2%, p = 0.01), peak volumetric blood flow (515.8 vs 317.2 ml/min, p = 0.007), and coronary flow reserve (2.93 +/- 0.74 vs 1.99 +/- 0.53, p < 0.001) were higher with adenosine than dipyridamole. Both agents caused similar decreases in systemic blood pressure and little change in heart rate. Adenosine appears to be a more potent coronary vasodilator than dipyridamole in denervated human transplant subjects. Adenosine has a vasodilator effect at the epicardial and microvascular levels, resulting in an overall increase in volumetric flow. Flow reserve in response to both endothelium-independent agents is decreased in comparison with previously established values, but the attenuation is greater with dipyridamole.
Adenosine↗
Subcutaneous infection with Mycobacterium abscessus in a renal transplant recipient.
Transplant recipients show a high incidence of infections, often with atypical manifestations mainly because of drug-related immunosuppression. Mycobacterial infections can be life-threatening in immunosuppressed patients due to the risk of dissemination. There have been only few reports of cutaneous infections with Mycobacterium abscessus among immunosuppressed patients. We present a rare case with a sporotrichoid skin infection with M. abscessus in a renal recipient. The value of immunohistochemical detection of mycobacteria using an anti-BCG antibody in the diagnostic work-up skin biopsies is demonstrated. Long-term antibiotic treatment resulted in complete remission, although recurrences with atypical presentation were observed.
Aged↗
Coronary stenting for coronary artery narrowing in a heart transplant recipient.
Transplant atherosclerotic coronary disease remains the leading cause of death in heart transplant recipients. We report the first case of coronary stent implantation in a heart graft for epicardial focal stenosis. Due to the lower rate of restenosis after stenting in the native coronary artery, we suggest that coronary stenting be considered an acceptable, first intention therapeutic option instead of angioplasty alone whenever possible.
Angioplasty, Balloon, Coronary↗
Ultrasound evaluation of vascular complications in pancreas transplant recipients.
Transplantation of the pancreas is progressively becoming one of the preferred options of treating the insulin addicted diabetes mellitus. Pancreas can be transplanted alone, or together with a kidney, the latter option becoming more successful in recent years. In this case, the successfully transplanted pancreas with the regulation of sugar, protects the kidney from further damage. Among the more important complications in the recipient of the graft, we can certainly include vascular complications. One of the most important non-invasive methods of early discovery of vascular complications on the pancreas is in the first place ultrasound. Early diagnosis with ultrasound enables timely appropriate treatment and therefore the survival of the transplant. Especially unavoidable and useful in everyday practice is the role of the modern forms of ultrasound such as the Gray-scale sonography, duplex Doppler imaging and sonographic guidance for percutaneous biopsy. Color and Doppler ultrasound have proved themselves in everyday use as a precious source of information for diagnosis of eventual vascular complications and the status of regional vasculature. Early diagnosis resulting from the ultrasound and the concurrent use of other laboratory and clinical findings enables us to timely recognize and preempt the consequences of vascular complications thereby increasing the chances of pancreatic survival.
Diabetes Mellitus, Type 1↗
Kaposi's sarcoma in organ transplant recipients. The Collaborative Transplantation Research Group of Ile de France.
OBJECTIVES: Kaposi's Sarcoma (KS) is a tumour of multicentric origin with increased frequency after organ transplantation. To date, only North American data from the Cincinnati Transplant Tumor Registry have given some information about this disease in organ transplant recipients, but its true prevalence still has to be determined. In order to analyze Kaposi's sarcoma after kidney, liver and heart transplantation, we performed a retrospective study using the oldest registry of organ transplant recipients in Europe. METHODS: Among all 7923 organ transplant recipients recorded in the Groupe Collaboratif de Recherche en Transplantation de l'Ile de France (GCIF) registry from 1968 to 1990, we analyzed the prevalence and the clinical characteristics of Kaposi's sarcoma in 6229 kidney, 727 liver and 967 heart transplant recipients. In the subgroup of kidney transplant recipients, we assessed the role of cyclosporine on disease evolution. RESULTS: Overall prevalence of Kaposi's sarcoma after organ transplantation was 0.52%, but it was significantly higher among liver (1.24%) than among kidney (0.45%) and heart (0.41%) transplant recipients. Chronic hepatitis B surface antigen carriers were more frequent in liver than in kidney transplant recipients who developed Kaposi's sarcoma (66% vs 21%, p < 0.03). Following kidney transplantation, Kaposi's sarcoma was more severe in patients receiving cyclosporine (n = 16) when compared with those under conventional immunosuppression (n = 12). CONCLUSION: True prevalence of Kaposi's sarcoma among European transplant recipients is high (0.52%) and appeared significantly higher in liver compared with other organ transplant recipients. Cyclosporine seems to increase severity of the disease among kidney transplant recipient.
Adult↗
Management of pregnancy in transplant recipients.
Transplantation offers the best prospect of pregnancy in fertile women with various types of end-stage organ disease. Based on data from the USA National Transplantation Pregnancy Registry, >70% of posttransplant pregnancies have a successful live birth. Greatest experience has been seen in transplants involving the kidney, followed by the liver and then heart. Most pregnancies do not affect graft function significantly but are associated with significant obstetric problems such as spontaneous abortions, premature deliveries, low birthweight, intrauterine growth retardation, preeclampsia, etc. Cesarian section is required in 30% to 50% of patients, due to obstetric or maternal concerns. Neonatal death is rare, but 30% to 50% of live births have complications. Thus, management requires a multidisciplinary team. Similar data have been documented in developed Asian countries such as Japan and Singapore. Although fertility is restored early (<6 months), the current recommendation is to wait for >/=1 year, if not 2 years, after transplantation before allowing pregnancy. Patients without evidence of graft dysfunction and hypertension are more likely to have successful outcomes. Acute rejections may occur but the incidence does not appear to be increased dramatically. Treatment should be to similar to that of nonpregnancy treatment. Further pregnancies may be considered in instances of good outcome for the graft, fetus, and mother. Significant experience and safety has been accumulated in treatment using cyclosporine, azathioprine, prednisolone, and tacrolimus. However, few data are available with regard to the newer immunosuppressants, such as mycophenolate mofetil, and thus these agents are not recommended. Most live births have normal growth and development. Although there is much information available on posttransplant pregnancy it is imperative that each center maintains its own registry of pregnancy and offspring outcomes.
Female↗
Long-term functional follow-up of lung transplant recipients.
Transplantation is now a treatment option in patients with end-stage pulmonary and pulmonary vascular disease. This article describes the outcome of single and double lung transplants performed by the Toronto Lung Transplant Group. Specifically reported are mortality, cause of death, pulmonary physiology, arterial blood gases, and exercise performance. Where possible, these results are compared with results of heart-lung transplantation from other centers.
Adult↗