Aspergillus endocarditis in lung transplant recipients: case report and literature review.

We present a case of endocarditis caused by Aspergillus in a lung transplant (LT) patient and review 6 previously reported cases. All cases were caused by Aspergillus fumigatus. Five patients (71%) were transplanted due to cystic fibrosis. None of the patients had any previously known valvular heart disease. The time that elapsed between LT surgery and the diagnosis of Aspergillus endocarditis was 8±6 months. Large peripheral emboli were observed in 6 patients (85%); blood cultures were negative in all. Transthoracic echocardiography did not detect the presence of vegetations in 3 patients (43%); the vegetations measured >1.5 cm in all cases. Five patients (71%) died from disseminated disease. Both survivors underwent combined therapy with antifungal drugs and surgical treatment.

Cutaneous aspergillosis in a lung transplant recipient.

Organ transplant recipients are at increased risk for Aspergillus infections. Cutaneous aspergillosis (CA) occurs less frequently and is poorly characterized. The case of a lung transplant recipient with CA is presented. Six months after transplantation, 3 painful skin nodules appeared, with 1 each in the right calf, left arm, and upper back. Exudate from the leg nodule yielded Aspergillus fumigatus. Computed tomography of the chest showed bilateral hilar lymphadenopathy, but <1 cm in size. The case could be the result of Aspergillus dissemination from a hypothetical asymptomatic pulmonary infection. The lack of lung radiological signs could be related to prophylactic treatment with inhaled liposomal amphotericin B, which could have prevented clinically evident Aspergillus lung infection. The patient was treated with voriconazole, which was maintained for 3 months. The patient recovered completely.

Hepatitis E Virus Infection in Lung Transplant Recipients: A Case Series.

BACKGROUND: Hepatitis E virus (HEV) is one of the common causes of acute and chronic viral hepatitis with a global distribution. Genotypes 1 and 2 only affect humans and produce acute hepatitis epidemics in endemic regions (Asia, Africa). In nonendemic areas (America, Europe), genotypes 3 and 4 are considered a zoonosis and cause sporadic acute hepatitis. HEV has been described in solid organ transplant recipients; however, data on lung transplant patients are limited. OBJECTIVE: To present the first 3 cases of HEV infection in lung transplant recipients in our unit. CASE PRESENTATION: We report 3 cases of HEV infection in post-transplant patients presenting with symptoms and alterations in liver enzymes. All patients have no history of travel outside Spain prior to observing abnormalities in the liver function. Diagnoses were made with in-home polymerase chain reaction and enzyme-linked immunosorbent assay (IgG/IgM). The first patient was not treated and died of progressive hepatic disease, with postmortem diagnosis of HEV infection complications. The other 2 patients were treated with ribavirin after the diagnosis of HEV infection. Ribavirin was discontinued in 1 patient because of anemia necessitating red blood cell transfusions. CONCLUSIONS: HEV should be considered in the differential diagnosis of patients with abnormal liver enzymes after transplant. Early detection and treatment have implications in the prevention of liver failure and mortality. Large prospective seroprevalence studies of HEV in lung transplant patients are warranted to recognize the epidemiology of this infection in lung transplant recipients.

Conversion from cyclosporine to tacrolimus stabilizes the course of lung function in lung transplant recipients with bronchiolitis obliterans syndrome.

Bronchiolitis obliterans syndrome (BOS) continues to be the main factor limiting the long-term survival of lung transplant recipients. The objective of this study was to prospectively assess the impact of conversion from cyclosporine (CsA) to tacrolimus on lung function in patients who developed BOS while receiving CsA-based immunosuppressive therapy. A total of 79 patients with BOS were included in the study. Sixty percent of patients had stage II or III BOS according to the International Society for Heart and Lung Transplantation criteria. Mean time from transplantation was 30.4 +/- 21.9 months and all patients were on CsA therapy at enrollment in the study, with mean trough levels of 232.75 +/- 98.26 ng/mL. After conversion, tacrolimus trough levels were 11.0 +/- 3.6 ng/mL at 3 months and 9.0 +/- 3.4 ng/mL at 12 months. Sixteen deaths occurred during the first year postconversion, 56% of which were due to respiratory failure. Comparison of forced expiratory volume in 1 second (FEV(1)) preconversion versus postconversion showed a change in the slope of the FEV(1)-time curve. The slope of the preconversion curve was -0.44 versus a zero slope, whereas the slope of the postconversion curve was 0.005, with a statistically significant difference between both slopes. This change in slopes, which was also seen in FEV(1%), suggests that lung function loss closed after conversion from CsA to tacrolimus supporting this therapeutic strategy in lung transplant recipients with BOS treated with CsA.

Epidemiology and Risk Factors for Cancer After Lung Transplantation.

Cancer is the third most common cause of death among lung transplant (LT) recipients who survive for more than 1 year. The purpose of this study was to analyze the incidence and risk factors for cancer after LT in a Spanish cohort. The epidemiology and risk factors for cancer were retrospectively analyzed in LT recipients from 2 cities in Spain, Madrid and Barcelona. Of the 1353 LT patients initially included in the study, 125 (9.2%) developed cancer after a mean of 3.7 years. This frequency was 5-fold higher than in the general population. The most prevalent tumors were skin cancer (32%), lymphoproliferative disease (18%), and lung cancer (16.5%). In 4 patients, lung cancer was diagnosed on the day of the operation. The risk of cancer increased with age >55 year (hazard ratio [HR] 2.89 [1.64-5.09]; P < .001), in men (HR 2.8 [1.4-5.6]; P = .004), and in heavy smokers (>20 pack-years) (HR 2.94 [1.64-5.27]; P < .001). Other factors such as sun exposure were not found to be risk factors. In conclusion, prevalence of cancer is high in LT recipients in a Mediterranean country. Skin tumors, lymphoproliferative disease, and lung cancer are the most prevalent cancers. Age, male sex, and smoking were the main risk factors for cancer in this population.

Is gammaglobulin anti-CMV warranted in lung transplantation?

UNLABELLED: The usefulness of anti-CMV hyperimmune gammaglobulin (IgG-CMV, Cytotec) in lung transplant patients (LTx) is controversial. The objective of this study was to analyze the effectiveness of IgG-CMV in our LTx receptors. PATIENTS AND METHODS: A retrospective study of LTx recipients treated with IgG-CMV as prophylaxis or as treatment for invasive disease. We used IgG-CMV associated with IV ganciclovir (GCV) as treatment for invasive disease. High-risk patients (CMV-negative recipients from CMV-positive donors; CMV-/+) were also with IgG-CMV prophylaxis during the first year. Other prophylactic uses of IgG-CMV were as an alternative to GCV in patients with related GCV toxicity, and as preemptive therapy in cases of persistent positive viral load (antigenemia > or = 1 cell and/or a PCR > or = 400) although oral GCV administration. RESULTS: Between January 2000 and August 2003, 14 of the 74 lung transplant recipients (19%) received IgG-CMV as treatment for invasive disease (4 cases: 2 gastritis, 1 esophagitis, 1 hepatitis) and/or as prophylaxis (14 cases). All patients treated for invasive disease evolved favorably. No therapeutic failure were observed in CMV-/+ patients during treatment. Three of the six patients treated with IgG-CMV developed positive antigenemia despite treatment. The four patients treated for persistent antigenemia while receiving oral GCV achieved neutralization during the first month of treatment. CONCLUSION: IgG-CMV associated with Gancyclovir is effective as treatment for invasive disease and as pre-emptive therapy in patients with persistent positive viral load. In CMV-/+ recipients, IgG-CMV prevents pneumonitis and delays the development of invasive disease after the first year.

[Lung transplant therapy for suppurative diseases]. / Trasplante pulmonar en enfermedades supurativas.

OBJECTIVE: Lung transplantation is a valid therapeutic approach for patients with bronchiectasis. The objective of the present study was to evaluate our experience with bronchiectasis patients and compare the results in patients with cystic fibrosis to results in those with bronchiectasis caused by other processes. PATIENTS AND METHOD: We carried out a retrospective study of bronchiectasis patients treated by lung transplantation in order to analyze demographic, functional and microbiological characteristics before and after transplantation, and survival. RESULTS: From 1991 to 2002 lung transplants were performed on 171 patients, 44 of whom had suppurative lung disease (27 had cystic fibrosis and 17 had bronchiectasis caused by other processes). There were no significant differences in the demographic variables between the 2 groups. At transplantation, lung function variables showed severe bronchial obstruction (mean [SD] forced expiratory volume in 1 second of 808 [342] mL and forced vital capacity of 1,390 [611] mL) and respiratory insufficiency (PaO2 at 52 [10] mm Hg and PaCO2 at 48 [9] mm Hg). Only PaO2 was significantly lower in patients with bronchiectasis from causes other than cystic fibrosis. Airway colonization was present in 91% of the patients; Pseudomonas spp germs were detected in 64% of the cases and were multiresistant in 9%. In the early postoperative period germs were isolated in 59% of the cases, half of which involved the same germ as had been isolated before transplantation. One year after lung transplantation, 34% of the patients continued to have bronchial colonization. Survival at 1 year was 79% and at 5 years, 49%, with no significant difference between the patients with cystic fibrosis and those with other suppurative diseases, nor between the patients with and without Pseudomonas colonization. Only 2 patients had died of bacterial pneumonia at 1 month after transplantation. CONCLUSIONS: Although airway colonization in patients with suppurative diseases complicates postoperative management, the results in terms of survival are good.

The role of keratinocyte differentiation in the expression of epitheliotropic viruses.

We have examined the growth of three epitheliotropic viruses in cultures of human epidermal keratinocytes: herpes simplex virus (HSV) type 1, adenovirus type 2 (Ad-2), and human papillomavirus (HPV) type 1. Differences were noted in the level of expression of each virus, and these differences may be related to a dependency or lack of dependency on keratinocyte differentiation for complete viral growth. Of the three viruses studied, HSV was the only one to replicate productively in all cells of the culture. Its expression was independent of keratinocyte differentiation. This is unlike Ad-2, which infected all cells in the culture but replicated productively only in the suprabasal cells. Basal keratinocytes were shown to be infected, but for unknown reasons, they appeared in most instances to be nonpermissive for Ad-2 replication. Infected basal keratinocytes became permissive when they reached a suprabasal position. Ad-2 appears to require keratinocyte differentiation for full expression in culture. Following infection with HPV, cultured keratinocytes showed no evidence of productive replication. However, 50 to 250 copies of HPV DNA could be detected in each cell (average) as stable nonintegrated molecules. Viral DNA replication has been shown to occur in the younger cells and not in the older, more differentiated keratinocytes. The failure of HPV to be fully expressed in culture may be related, in part, to incomplete differentiation of the keratinocyte in vitro. The major conclusions of this study are (1) that keratinocyte differentiation is likely to play a role in the expression of some epitheliotropic viruses in culture, and (2) that keratinocyte differentiation may be a factor in the pathogenesis of certain viral diseases of keratinizing epithelia.

Healing potential of surgically-induced periodontal osseous defects in animals using mineralized collagen gel xenografts.

This experiment tested the capacity of a calf-skin collagen-mineral gel to induce bone regeneration within surgically-created periodontal defects in one dog and four monkeys. No bone regeneration occurred within 8 to 14 weeks. Healing primarily consisted of soft connective tissue formation and re-epithelialization. Notched defects on root surfaces did not repair with cementum and were always foci of inflammation.

Transplantation of enzyme-treated teeth in the monkey Macaca fascicularis.

Homologous tooth transplants evoke immunogenic rejection against antigens within donor periodontal ligaments cells and ground substance. Eight maxillary incisors of 6 juvenile animals were extracted, crowns and pulps removed by gutta percha; the roots were incubated serially in enzyme solutions and glutaraldehyde at 37 degrees C for 5 h to destroy cells, glycoproteins and proteoglycans. Seven control teeth from the same 6 animals were incubated in saline at 37 degrees C for 15 min. All teeth were then speedily transplanted to other animals which were killed at 6 wk or 3 months. Radiographs and histologic sections revealed extensive resorption and inflammation of all control teeth. Enzyme-treated teeth showed less inflammation with resorption mostly on the surface of the cut coronal dentine. A loose fibrous attachment usually formed on most aspects of the root surface with deposition of new cellular cementum within the donor ligament. Inflammation, where present, may have resulted from incomplete removal of periodontal ligament cells, ground substance, or from salivary bacterial contamination.

Rapamycin in lung transplantation: preliminary results.

INTRODUCTION: Rapamycin is a potent immunosuppressive agent with a different mechanism of action and different adverse effects from those of calcineurin inhibitors (CNIs). OBJECTIVE: To analyze our experience with rapamycin in patients undergoing lung transplantation and heart-lung transplantation in our center. PATIENTS AND METHODS: Patients were treated with rapamycin when showing chronic rejection and/or toxicity associated with the CNI after lung transplantation or heartlung transplantation. Patients with chronic rejection were administered rapamycin in combination with CNIs, whereas the CNIs were eliminated in patients with toxicity. RESULTS: Since October 2001, 7 patients (4 women), of mean age 45+/-15 years, received treatment with rapamycin (heart-lung transplantation, 2 cases; lung transplantation, 5 cases). The indications were chronic rejection in 4 patients and CMIs toxicity in 3 patients (kidney failure in 2 cases and optic neuropathy in 1 case). Pulmonary function stabilization was observed in 3 of 4 patients receiving rapamycin for chronic rejection. In the 3 patients with CNIs toxicity elimination of these drugs did not result in pulmonary functional deterioration. Patients with kidney failure showed an improvement in creatinine levels; visual acuity improved in the patient with optic neuropathy. We observed 2 infectious complications (pneumococcal pneumonia and pulmonary aspergillosis), which resolved with treatment. CONCLUSION: Rapamycin is an alternative for lung-transplant recipients who develop chronic rejection and/or CNIs toxicity.

[Pulmonary sarcoidosis and antiphospholipid syndrome]. / Sarcoidosis pulmonar y síndrome antifosfolipídico.

Pulmonary sarcoidosis is an idiopathic granulomatosis with a clinical picture involving dyspnea, coughing, chest pain and characteristic radiologic changes. A review of English and Spanish language publications (PubMed 1990 through 2002) suggests that our report of a case of pulmonary sarcoidosis associated with primary antiphospholipid syndrome is the first one in the literature for this period. The patient was a 35-year-old man with venous thrombosis who later developed pulmonary sarcoidosis. The clinical course was not favorable in spite of good prognostic factors. We conclude that the association of these two clinical conditions is rare and that the presence of antiphospholipid syndrome may lead to greater morbidity and mortality.

Phenylephrine in the prevention of hypotension following spinal anesthesia for cesarean delivery.

STUDY OBJECTIVE: Phenylephrine and ephedrine were compared in the prevention of maternal hypotension following spinal anesthesia for elective cesarean delivery. DESIGN: Randomized, double-blind trial. SETTING: Obstetric suite at a university-affiliated hospital. PATIENTS: Sixty healthy patients electively scheduled for cesarean delivery under spinal anesthesia. INTERVENTIONS: Patients were randomly assigned to receive either ephedrine (n = 29) in 10 mg intravenous (IV) bolus injections or phenylephrine (n = 31) in 80 microgram IV bolus injections to maintain systolic blood pressure (SBP) above 100 mmHg. MEASUREMENTS AND MAIN RESULTS: Maternal venous, umbilical artery, and umbilical vein blood gases were measured, and neonatal Apgar scores and Early Neonatal Neurobehavior Scale scores were assessed. In the ephedrine group, umbilical artery pH was 7.28 +/- 0.01 (mean +/- SEM), umbilical artery partial pressure of carbon dioxide (PCO2) was 56.6 +/- 1.4 mmHg, and umbilical artery base deficit was 2.2 +/- 0.04 meq. In the phenylephrine group, umbilical artery pH was 7.32 +/- 0.01, umbilical artery PCO2 was 52.1 +/- 1.3 torr, and umbilical artery base deficit was 0.38 +/- 0.35 meq. There were significant differences between the groups in mean umbilical artery pH, PCO2, and base deficit, although all values obtained were within normal limits. There were no significant differences between the groups in the remaining acid-base values, neonatal Apgar scores, Early Neonatal Neurobehavior Scale scores, or frequency of maternal nausea and vomiting. CONCLUSIONS: Phenylephrine is as effective as ephedrine in the treatment of maternal hypotension, and when used in small incremental bolus injections, it appears to have no adverse neonatal effects in healthy, nonlaboring parturients.

Recommendations on the use of everolimus in lung transplantation.

The antiproliferative effect of everolimus provides a therapeutic option in the immunosuppression therapy of lung transplantation, by reducing both the risk of acute rejection and the process of progressive fibrosis that determines chronic graft rejection. However, few data on the use of everolimus in lung transplantation have been published to date, and the specific indications of the drug, along with the most adequate time for its introduction or dosing, have not been defined yet. The aim of this article is to propose recommendations for the use of everolimus in lung transplant recipients, including indications, dosing schedules and the use of concomitant immunosuppression. This consensus document has been developed by experts of all the Spanish lung transplant groups from the review of the existing literature and the clinical experience.

Pulmonary oedema after lithotripsy in a patient with hypertrophic subaortic stenosis.

Pulmonary oedema in a patient with hypertrophic subaortic stenosis undergoing extracorporeal shock wave lithotripsy is described. This event occurred upon emergence from the bath. It is suggested that pulmonary oedema followed emergence because of a reduction in central venous pressures and a decrease in preload which led to transient dynamic obstruction. Treatment with beta adrenergic blockade reduced outflow tract obstruction. Anaesthetists should be aware of the haemodynamic consequences of immersion and emersion with extracorporeal shock wave lithotripsy.

Intraspinal opioids: implications for monitoring. Monitoring in the intensive care unit is essential.

Patients receiving intraspinal opiates should be monitored in the intensive care unit for at least 24 hours to prevent potentially lethal outcomes. These include respiratory depression caused by sequestration of the morphine in the cerebrospinal fluid and migration of epidural catheters in the subarachnoid or intravascular space. At this time, most hospitals are not equipped or staffed adequately to guarantee the safety of these patients outside the intensive care unit.