Trauma management in solid organ transplant recipients

The recognition that cell death in the myocardium is not only necrotic in nature but is also mediated by activation of the suicide program of myocytes has raised several questions concerning the magnitude of this phenomenon, and whether these two distinct forms of cell death are disease-dependent or coexist in the pathologic heart. Additionally, the times required for the completion of apoptotic and necrotic myocyte cell death are unknown, making the analysis of their respective rates in the myocardium impossible at present. The documentation that mechanical forces in vitro, mimicking diastolic Laplace overloading in vivo, can transmit a death signal to myocytes suggests that programmed cell death may be triggered in the stressed myocardium independently from the etiology of the overload. Because increasing pressure or volume loads, or both, in the failing heart induce myocyte hypertrophy and proliferation, a challenging question is whether the induction of genes regulating these cellular growth processes may activate programmed cell death as well. Finally, the identification of the mechanisms responsible for the translation of a diffuse environmental condition into a death signal in a limited number of cells scattered across the ventricular wall is a major challenge of future research.     

Skin cancers in organ transplant recipients

Organ transplant recipients on immunosuppressive therapy are prone to skin cancers, especially squamous cell carcinomas developing on sun-exposed areas. Their frequency increases with time after transplantation reaching 40-70% of the patients after 20 years. Squamous cell carcinomas tend to be multiple and may have a life-threatening course. Most studies concern kidney transplant recipients but new data are now available on recipients of other organs. Carcinogenic factors include mainly immunosuppressive treatments, UV light and human papillomaviruses; the role of genetic factors is more equivocal. Melanomas and other rare tumors such as Merkel cell tumors or sarcomas are also increased. Surgical excision with histological examination represents the treatment of choice. When lesions become multiple and/or aggressive, additional therapeutic methods are necessary, such as topical or oral retinoids and in some cases, reduction of the immunosuppressive treatment. Radiotherapy should be reserved to limited cases. Prevention must be undertaken by a regular dermatological examination and sun protection.     

Recurrent Epstein-Barr virus-associated lesions in organ transplant recipients

This paper discusses the problem of violence and its expression upon mortality due to external causes. A few indicators are offered, which have been worked upon it to emphasise the importance of the theme. In a general way, the study demonstrates violent death has had its magnitude increased along the years, not only throughout Latin America but also in Brazil and in Santa Catarina.     

Delayed acquisition of high-avidity anti-cytomegalovirus antibody is correlated with prolonged antigenemia in solid organ transplant recipients

Previous studies have demonstrated that maturation of cytomegalovirus (CMV)-specific antibodies in solid organ transplant recipients is delayed after primary CMV infection. To investigate the clinical significance of this finding, the avidity indices of anti-CMV antibody were determined in parallel with other serologic and virologic parameters in serial serum samples from 24 solid organ transplant recipients who had primary CMV infection that began during the first 3 months after transplantation. The data obtained show that a delay in antibody maturation is significantly correlated with a long persistence of positive antigenemia.     

Antimicrobial strategies in the care of organ transplant recipients

OBJECTIVE: To evaluate amniotic fluid lamellar body counting as a fetal lung maturity test. Lamellar body particles can be rapidly counted using the platelet channel of most blood cell analyzers. METHODS: We conducted a 3-year prospective clinical outcome study. During the interval under study, outcomes of 247 neonates were used to evaluate the test; 28 neonates developed respiratory distress syndrome (RDS). Lecithin-sphingomyelin ratio (L/S) was available for 187 cases. RESULTS: All cases of RDS had lamellar body counts of 55,000/microL or less and L/S of 2.2 or less; 59% of cases with no RDS had counts greater than 55,000/microL and 70% of normal cases had L/S higher than 2.2. CONCLUSION: Use of lamellar body counts is justified as a rapid screening test to predict fetal lung maturity. Immature results should be followed by a more specific test such as L/S.     

Infectious complications occurring in liver transplant recipients receiving mycophenolate mofetil

PURPOSE: To determine the causes of visual impairment in a population-based group of visually impaired preterm children. METHODS: Ophthalmological examination and magnetic resonance imaging or computed tomography of the brain were performed in all visually impaired preterm children born 1989-95 in V?rmland. RESULTS: Ten of 18 children had periventricular leukomalacia affecting the optic radiation, six had other lesions or malformations in the posterior visual pathways/cortex, but no child had visually impairing retinopathy of prematurity. CONCLUSION: We conclude that cerebral lesions or malformations are common causes of the visual functional deficit in visually impaired children born preterm. Brain damage should be suspected in a prematurely born child who presents with either of the signs: fixation difficulties, strabismus or nystagmus.     

Long-term renal function in heart transplant recipients receiving cyclosporine therapy

BACKGROUND: Immunosuppression with cyclosporine has improved allograft function and reduced both morbidity and mortality in organ transplantation. However, cyclosporine-induced nephrotoxicity still is a concern. The purpose of our study was to evaluate the effects of cyclosporine on renal function in orthotopic heart transplant recipients. METHODS: Thirty-nine patients who received transplants from 1985 to 1991 and had at least three yearly glomerular filtration rate measurements posttransplantation by 125I-iothalamate clearance method were included in the study. In addition, serum creatinine (before and after transplantation) and cyclosporine doses were analyzed. RESULTS: Maintenance immunosuppression at 1 year consisted of prednisone (0.1 mg/kg/day), azathioprine (2 mg/kg/day), and cyclosporine (12-hour trough level 100 to 150 ng/ml by fluorescence polarization immunoassay). The mean serum creatinine at 1 year was significantly higher than the mean pretransplantation serum creatinine (1.51 +/- 0.32 versus 1.28 +/- 0.38, p < 0.05) and stabilized after the first year. The mean glomerular filtration rate by 125I-iothalamate clearance method was 70.6 +/- 20.3 ml/min/1.73 m2 (range 32 to 105) at 1 year and remained relatively stable during the follow-up period of up to 7 years. Creatinine clearance calculated by the Cockcroft and Gault formula overestimated the true glomerular filtration rate after the third year. The mean cyclosporine dosage was significantly lower after the first-year dose of 3.9 +/- 1.8 mg/kg/day (p < 0.05). Three patients in 39 started hemodialysis at 5, 7, and 10 years after transplantation. CONCLUSION: Our data indicate that the adequacy of renal function is preserved with long-term cyclosporine therapy in heart transplant recipients.     

Predictors and outcome of early- versus late-onset major bacterial infections in liver transplant recipients receiving tacrolimus (FK506) as primary immunosuppression

Major bacterial infections and the predictors of early (within 100 days of transplantation) versus late onset (after 100 days post-transplant) bacterial infections were prospectively assessed in 130 consecutive liver transplant recipients receiving tacrolimus (FK506) as primary immunosuppression. The median follow-up period was 38 months. Overall, 35% (45/130) of the patients developed 67 episodes of major bacterial infections (0.52 episodes/patient). Sixty-three percent of the major bacterial infections occurred early, and 37% occurred in the late post-transplant period. Eighty-four percent of the abdominal infections occurred early, whereas 38% of the cases of pneumonia, 60% of the cases of primary bacteremia, and 50% of the biliary infections occurred late. By logistic regression analysis, portal vein thrombosis was the most significant independent risk factor for early-onset major bacterial infection (odds ratio 4.1; 95% CI 1.4-12.2), and recurrent hepatitis C was the most significant independent predictor of late-onset major bacterial infections (odds ratio 6.21; 95% CI 1.9-20.2). Thus, sources and risk factors differ for early versus late-onset bacterial infections after liver transplantation. Knowledge of the differences in the potential sources, the pathogens, and the predictors of early versus late-onset bacterial infections can be valuable in the evaluation and empiric treatment of liver transplant recipients with bacterial infections.     

Clinical observations of metabolic changes occurring in renal transplant recipients receiving ketoconazole

Metabolism of cyclosporine is reduced by ketoconazole binding to the monooxygenase responsible for cyclosporine degradation. This isozyme of cytochrome P450, along with other similar monooxygenases, is involved in the regulation of the synthesis and degradation of important metabolic pathways of cholesterol. Monooxygenases throughout these pathways are inhibited by ketoconazole binding causing a decreased metabolism of calcitriol, bile acids, and steroid hormones, and can thereby potentiate altered lipid metabolism, bone metabolism, and weight status of transplant recipients. A group of renal transplant recipients taking ketoconazole (n=25) was compared with a matched cohort not receiving ketoconazole for metabolic changes during the first six months posttransplantation. Lower LDL cholesterol levels were seen in the ketoconazole group (109 +/- 8 mg/dl) than the no ketoconazole group (140 +/- 8 mg/dl) at one month but this difference was not sustained at six months. More bone loss occurred in the ketoconazole group as demonstrated by significant changes in bone density as well as a greater urinary appearance of bone collagen crosslink, deoxy-pyridinoline (29 +/- 4 nmol dpd/mmol creatinine and 18 +/- 4 at six months for the ketoconazole group versus the no ketoconazole group, respectively, P<0.05). Weight gain changes were different between the ketoconazole group and no ketoconazole group (6.4 +/- 1.4 kg versus 5.0 +/- 1.3 kg) at six months and an increased rate of weight gain over time in the ketoconazole group (0.02 kg/day at one month versus 0.05 kg/day at six months, P<0.007). Effectiveness of ketoconazole inhibition of cyclosporine is valuable, but inhibition of other metabolic pathways should be evaluated as well.     

Respiratory syncytial virus-associated infections in adult recipients of solid organ transplants

OBJECTIVES: To define discrete developmental levels of understanding of the ways in which normal children and adolescents link autonomy and will to moral obligation and to study the correlation between this progression and previously identified stages of conscience conceptualization. METHOD: One hundred thirty-two normal volunteers between the ages of 5 and 17 years were individually interviewed using the moral volition section of the semistructured Stilwell Conscience Interview. Analysis of the interviews resulted in five levels of understanding of moral self-evaluation and volitionally chosen behavior. RESULTS: Analyses of variance and covariance showed that the five levels of moral volition had significant correlation with five conceptualization stages, with stage criteria showing a stronger correlation than age. Self-identified tasks of oughtness were hierarchically defined beginning with those defining a morality of restraint followed by moralities of mastery/sufficiency, virtuous striving, idealization, and individual responsibility. Perception of increased independence of self in interaction with conscience was noteworthy at stages 4 and 5. CONCLUSIONS: Moral volition is the domain of conscience functioning that defines understanding of moral self-evaluation and volitionally chosen actions; five levels of understanding can be demonstrated in normal children between the ages of 5 and 17 years.