Role of pulmonary function in the detection of allograft dysfunction after heart-lung transplantation

BACKGROUND: Lung function is altered by infection and rejection in patients who undergo heart-lung transplantation. The sensitivity, specificity, and positive/negative predictive values (PPV and NPV) of lung function for the detection of allograft dysfunction in these patients were measured. METHODS: Thirty three patients who underwent heart-lung transplantation were followed for a mean period of 16.3 months. On 123 occasions functional measurements were obtained at the time a transbronchial biopsy specimen and/or bronchoalveolar lavage fluid was taken, which were used as gold standards. Optimal sensitivity (the value for which sensitivity equals specificity) was computed for each functional test from receiver-operator characteristic (ROC) curves. RESULTS: Acute rejection was present on 31 occasions and infection on 36 occasions; 56 samples were normal. Infection and rejection were accompanied by airflow obstruction, a rise in the slopes of the alveolar plateaus for nitrogen, hexafluoride sulphur and helium (SN2, SSF6, and SHe), and a decrease in the difference between SSF6 and SHe (delta S), total lung capacity (TLC), and lung transfer factor (TLCO). Optimal sensitivities for SHe, mid forced expiratory flow (FEF25-75), TLC, and forced expiratory volume in one second (FEV1) were 68%, 67%, 66%, and 60%, respectively; they were not different for infection and rejection and did not change over the study period. For infection and rejection together, PPV ranged from 72% to 88% and NPV from 27% to 52% according to the functional test and the postoperative period considered. CONCLUSIONS: Indices of ventilation distribution, FEF25-75, and TLC have the best optimal sensitivity for the diagnosis of infection and rejection after heart-lung transplantation. The high PPV of pulmonary function in detecting allograft dysfunction observed in this study suggests that a diagnostic procedure should be performed whenever one or more functional tests deteriorate; conversely, the low NPV indicates that a stable pulmonary function does not rule out allograft dysfunction.


     

L-arginine supplementation in young renal allograft recipients with chronic transplant dysfunction.

AIMS: L-arginine (LA), the precursor of nitric oxide (NO), was suggested to be beneficial in many forms of renal disease: hypertension, ureteral obstructive nephropathy and cyclosporin A (CsA) nephrotoxicity. METHODS: Thus, we investigated the effects of LA supplementation on renal function, proteinuria and blood pressure (BP) in young renal allograft recipients with chronic renal transplant dysfunction treated with CsA. Eleven CsA-treated renal allograft recipients with chronic transplant dysfunction, aged 11-22 years, were randomly assigned to a 6-week treatment period with placebo (P), followed by 2 subsequent 6-week periods with LA supplementation (0.1 g/kg body weight/day) or a 6-week treatment period with LA, followed by 2 subsequent 6-week periods with P. At the end of each treatment period 24-hour BP recordings were made, and GFR (Inutest), RPF (PAH clearance) and the urinary excretion of protein, albumin, nitrate, cGMP and urea were evaluated. RESULTS: In comparison to placebo, LA treatment did not significantly change GFR, RPF, proteinuria and albuminuria, mean systolic or diastolic BP. The urinary excretion of urea and NO3 increased after LA supplementation (uUrea: LA 26.3 +/- 4.6 compared to P 23.5 +/- 4.7 g/day/1.73 m3, p < 0.05, uNO3: LA 514 +/- 152 compared to P 95 +/- 41 mM/day/1.73 m3, p < 0.05), whereas urinary excretion of cGMP remained unchanged. CONCLUSION: LA supplementation did not improve renal function and did not decrease proteinuria in CsA-treated renal allograft recipients with chronic transplant dysfunction possibly because of inhibition of NO-cGMP forming mechanism.     

Bilateral lung transplant for bronchiectasis in asymmetric thorax: a case report

Patients with suppurative lung diseases such as bronchiectasis and cystic fibrosis can be treated surgically, which leads to an asymmetric thorax, making lung transplant difficult in a volume-reduced hemithorax. We report a 52-year-old man with bronchiectasis and ventilation, dependent on a severe asymmetric thorax, who underwent bilateral lung transplant without cardiopulmonary bypass or extracorporeal membrane oxygenation support. This report suggests that bilateral lung transplant might be an efficient therapeutic option for such patients. Lung transplant is generally accepted as an effective way to deal with end-stage pulmonary diseases. Particularly, in patients with bronchiectasis or cystic fibrosis, single lung transplant may lead to infectious complications more easily. Thus, bilateral lung transplant is a better choice for such patients. However, some patients with bronchiectasis may have a history of surgical resection of target areas, which leads to an asymmetric thorax and makes lung transplant more difficult. We described 1 case of bilateral lung transplant for bronchiectasis in asymmetric thorax.     

The use of milrinone in a patient with mitral regurgitation and severe pulmonary hypertension: a case report

A 65-year-old female with mitral regurgitation was scheduled for the mitral valve surgery. However, because of the severe pulmonary hypertension, the patient needed evaluation on the reversibility of pulmonary hypertension and the safety of the surgical procedure. Milrinone, a phosphodiesterase inhibitor with vasodilating and positive inotropic properties, known to lower pulmonary vascular resistance was administered to the patient. Milrinone showed a prompt decrease of pulmonary artery pressure and an increase of cardiac output, and the cardiac surgery was performed uneventfully. It is considered that milrinone is useful in lowering pulmonary vascular resistance and assessing the reversibility of pulmonary hypertension in patients with severe pulmonary hypertension undergoing cardiac surgery.     

Gastric pacing for severe gastroparesis in a heart-lung transplant recipient.

Gastroparesis is a serious complication of lung and heart-lung transplantation that can lead to malnutrition, gastroesophageal reflux, aspiration pneumonia and deteriorating lung function. Some patients with severe gastroparesis have symptoms that are refractory to dietary modifications and gastric promotility agents and require surgery. We describe the successful use of gastric pacing for the management of intractable gastroparesis, malnutrition and recurrent aspiration in a heart-lung allograft recipient. Lung transplant recipients with severe gastroparesis may benefit from gastric pacing.     

Recipient ureterocalycostomy in a renal allograft: case report of a transplant salvage

The use of a recipient ureter ureterocalycostomy in the management of ureteral obstruction in a renal transplant recipient is presented. This technique can be used when primary modes of reconstruction are unavailable and nephrectomy is the only alternative.     

Diagnosis and treatment of allograft rejection in heart-lung transplant recipients

Six patients received heart-lung transplants between March, 1981, and January, 1982. There were four women and two men between 26 and 45 years of age, three with primary pulmonary hypertension and three with congenital heart disease and pulmonary hypertension (Eisenmenger's syndrome). Immunosuppression was primarily with cyclosporin-A, with additional corticosteroid, azathioprine, and rabbit antihuman thymocyte globulin. Six episodes of allograft rejection in four patients (10, 11, 21, 24, 53, and 86 days after transplantation) were detected by means of transvenous endomyocardial biopsy. All patients experienced pulmonary edema early after transplantation (reimplantation response), and two patients required mechanical ventilatory support for allograft rejection at 10 and 11 days. Treatment of rejection consisted of intravenous methylprednisolone (four episodes) or augmented oral prednisone (two episodes), with resolution. No episode thought to be pulmonary rejection has occurred in the absence of cardiac findings. Four patients are alive from 6 to 15 months after transplantation and are functionally normal. Early experience with heart-lung transplantation suggests (1) that allograft rejection can be detected by cardiac findings and successfully treated by augmented corticosteroids, (2) that lung rejection does not occur in the absence of cardiac findings, (3) that the frequency and severity of rejection episodes are not greater than with standard cardiac transplantation, and (4) that the frequency of rejection episodes is highest within the first 60 days after transplantation.     

Effect of pentoxifylline on graft function of renal transplant recipients complicated with chronic allograft nephropathy

BACKGROUND: Chronic allograft nephropathy (CAN) is characterized by a progressive deterioration of renal function with various degrees ofproteinuria. Currently, there is no effective treatment despite the introduction of new generations of immunosuppressants. Pentoxifylline (PTX) is a phosphodiesterase inhibitor that possesses antiproteinuric effect and has been proved to be effective in treating several glomerular diseases. The purpose of the current study was to examine the effect of PTX on renal transplant patients with established CAN. MATERIALS AND METHODS: Renal transplant recipients with biopsyproven CAN were recruited for the study. All the patients had been on angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for more than 1 year and were on a triple immunosuppressive regimen including corticosteroid, calcineurine inhibitor and mycophenolate mofetil. PTX in a dose of 1,200 mg/day was administered for at least 6 months. The following parameters were assessed at baseline, the 3rd and the 6th month post treatment: systolic and diastolic blood pressure, number of anti-hypertension drugs, serum creatinine (sCr),estimated glomerular filtration rate (eGFR), 24-hour urinary protein excretion (U/P), urinary N-acetylglucosaminidase (NAG) and intracytoplasmic Thl/Th2 cytokines production of peripheral blood CD4+ cells. RESULTS: A total of 17 (11 male and 6 female) patients were enrolled in the study. The mean duration of follow-up post transplant was 10.6+/- 4.4 years. The baseline data of sCr, eGFR and U/P were 1.83+/-0.46 mg/dl, 38+/-8 ml/min and 2.65+/-2.15 g/day, respectively. Corresponding values at the 3rd and 6th month post treatment were 1.90+/-0.43 mg/dl (p = NS), 33+/-7 ml/min (p=NS), 2.13 +/-1.13 g/day (p < 0.05) and 2.03+/-0.64 mg/dl (p < 0.05), 32+/-10 ml/min (p < 0.05), 2.74 +/-0.93 g/day (p = NS), respectively. When individual data were analyzed, five cases (29.4%) showed a U/P significant reduction of more than 50% of baseline value, while in 10 cases (58.8%) the graft function remained either stable (9 cases) or improved (1 case) at the end of treatment. Urinary NAG was elevated at the 3rd month, but stabilized thereafter. The Thl/Th2 intracytoplasmic cytokine pattern of peripheral blood CD4+ cells showed a significant decrease of cells bearing TNF-alpha (15.0+/-14.4% vs 14.2+/-17.0%, p < 0.05) and cells bearing IL-10 (1.60 +/-1.23% vs 0.90+/-0.66%, p < 0.05) at the 3rd month. CONCLUSION: In this pilot study, PTX seemed to be temporarily effective in reducing proteinuria. The graft function was stabilized in more than half of patients at the end of follow-up.     

Malignant hyperthermia in a liver transplant patient: a case report

Malignant hyperthermia is an autosomal dominant disorder with incomplete penetrance and variable expression. This syndrome is characterized by a hypermetabolic response to all commonly used inhalational anesthetics and depolarizing muscle relaxants. It can happen during or after the anesthesia. We describe a case of malignant hyperthermia during orthotopic liver transplantation. Our patient was a 48-year-old man, born in Brazil but with European ascendance, who developed malignant hyperthermia associated with the use of isoflurane. He was treated with dantrolene, which caused hepatic graft dysfunction. It is important that transplant teams be able to recognize and treat this complication.     

Peritoneal leiomyosarcoma in a kidney transplant patient: a case report

Sarcomas are rare neoplasms, accounting for a 1.7% incidence among all transplanted patients presenting with de novo malignancies. Our present report focused on a 46-year-old woman who received immunosuppressive therapy based on cyclosporine and steroids for renal transplantation. Eight years after transplantations, she suffered lower abdominal pain and a mass involving peritoneal soft tissues was located near the right iliac vessels. Upon radical tumor excision, the histological examination revealed a high-grade leiomyosarcoma. Immunosuppression was reduced and cyclosporine switched to rapamycin. After 30 days, a computed tomography scan revealed two small pulmonary metastases, so the patient received adriamycin. Six months after the diagnosis, there was no intra-abdominal relapse and the pulmonary metastasis remain stable. The function of the transplanted kidney was normal and the patient was listed for laparoscopic pulmonary resection. Sarcomas in solid organ transplant patients appear to have aggressive features with 62% being high grade and 40% metastatic at the time of primary diagnosis with a recurrence rate of 30% and a 5-year survival rate of 25%. Patients diagnosed with sarcoma should be treated with multimodality therapy. After aggressive surgery whenever possible, a combination of a traditional cytotoxic drug and a "signal" blocking agent like rapamycin may increase selectivity toward tumor cells.     

Tacrolimus-associated myositis: a case report in a renal transplant patient

A 55-year-old Caucasian man who had received a second kidney graft in July 1993, was switched from cyclosporine to tacrolimus in June 2000 due to deterioration of renal function. Thereafter, he began to complain of muscle cramps in both quadriceps with an increased CPK and EMG findings of polyneuropathy. A muscle biopsy demonstrated acute myositis. Prednisone was administered with amelioration of the patient's symptoms, but with persistently increased CPK and myoglobin levels. In February 2001, mycophenolate mofetil was introduced and tacrolimus tapered to 3 mg daily to seek a toxic role of this immunosuppressant, since there was no other cause of myositis. A sudden decrease in CPK was observed, but the complete normalization took place only after its withdrawal in September 2002. This case represents a tacrolimus-associated myositis.     

Cytomegalovirus disease with atypical presentation in a renal transplant patient: case report

Infection is a major problem after kidney transplantation. Cytomegalovirus (CMV) is the most common viral infection affecting transplant patients. This report presents a rare clinical manifestation of CMV in the form of a hemorrhoid in a 58-year-old woman. One week after undergoing an external hemorrhoidectomy, the patient presented with fever, leukopenia, and thrombocytopenia. Pathological analysis showed CMV in the hemorrhoidal tissue, which was confirmed via a positive PP65 antigenemia assay. Therapy with ganciclovir (250 mg IV b.i.d. for 2 weeks) was started. The patient's response to treatment was good, and she has been doing well since that time. Her plasma creatinine level 2 years later was 79.2 micromol/L (normal range, 53-106 micromol/L). Physicians must always be aware of the hazards of CMV in immunocompromised patients with typical, and even with atypical, presentations. Taking into consideration the statement, "prophylaxis precedes treatment," nephrologists must try to detect CMV in their patients (especially during the first 6 months after transplantation) prior to the appearance of any clinical manifestations. If CMV is detected, pre-emptive therapy with ganciclovir should be started.     

Ventriculoperitoneal shunt dysfunction in a patient presenting with neurogenic pulmonary edema. Case report

The authors report on a patient with dysfunction of a ventriculoperitoneal shunt who presented with two episodes of neurogenic pulmonary edema within the space of a few months. The edema resolved on correction of the shunt dysfunction. Because neurogenic pulmonary edema may be a rare consequence of shunt dysfunction, it is important to recognize this unusual association and provide appropriate diagnostic measures and treatment.     

Bronchiolar carcinoma: a case report with pulmonary function studies

A patient with bilateral multinodular bronchiolar carcinoma is described in whom carbon monoxide transfer factor and arterial oxygen saturation were greatly impaired but lung volumes and ventilation were only minimally reduced. We record this because we have not found previous reports of detailed pulmonary function studies in this condition.