In vitro differentiation of rat spermatogonia into round spermatids in tissue culture.

STUDY QUESTION: Do the organ culture conditions, previously defined for in vitro murine male germ cell differentiation, also result in differentiation of rat spermatogonia into post-meiotic germ cells exhibiting specific markers for haploid germ cells? SUMMARY ANSWER: We demonstrated the differentiation of rat spermatogonia into post-meiotic cells in vitro, with emphasis on exhibiting, protein markers described for round spermatids. WHAT IS KNOWN ALREADY: Full spermatogenesis in vitro from immature germ cells using an organ culture technique in mice was first reported 5 years ago. However, no studies reporting the differentiation of rat spermatogonia into post-meiotic germ cells exhibiting the characteristic protein expression profile or into functional sperm have been reported. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Organ culture of testicular fragments of 5 days postpartum (dpp) neonatal rats was performed for up to 52 days. Evaluation of microscopic morphology, testosterone levels, mRNA and protein expression as measured by RT-qPCR and immunostaining were conducted to monitor germ cell differentiation in vitro. Potential effects of melatonin, Glutamax® medium, retinoic acid and the presence of epidydimal fat tissue on the spermatogenic process were evaluated. A minimum of three biological replicates were performed for all experiments presented in this study. One-way ANOVA, ANOVA on ranks and student's t-test were applied to perform the statistical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Male germ cells, present in testicular tissue pieces grown from 5 dpp rats, exhibited positive protein expression for Acrosin and Crem (cAMP (cyclic adenosine mono phosphate) response element modulator) after 52 days of culture in vitro. Intra-testicular testosterone production could be observed after 3 days of culture, while when epididymal fat tissue was added, spontaneous contractility of cultured seminiferous tubules could be observed after 21 days. However, no supportive effect of the supplementation with any factor or the co-culturing with epididymal fat tissue on germ cell differentiation in vitro or testosterone production was observed. LIMITATIONS, REASONS FOR CAUTION: The human testis is very different in physiology from the rat testis, further investigations are still needed to optimize the organ culture system for future use in humans. WIDER IMPLICATIONS OF THE FINDINGS: The successful differentiation of undifferentiated spermatogonia using the testis explant culture system might be employed in future to produce sperm from human spermatogonia as a clinical tool for fertility preservation in boys and men suffering infertility. LARGE SCALE DATA: None. STUDY FUNDING AND COMPETING INTERESTS: This work was supported financially by the Frimurare Barnhuset in Stockholm, the Paediatric Research Foundation, Jeanssons Foundation, Sällskåpet Barnåvard in Stockholm, Swedish Research Council/Academy of Finland, Emil and Wera Cornells Foundation, Samariten Foundation, the Swedish Childhood Cancer Foundation as well as through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet. All authors declare no conflicts of interests.

Impact of hemoglobin levels on outcomes of adjuvant chemotherapy in resected non-small cell lung cancer: the JBR.10 trial experience.

BACKGROUND: Cisplatin-induced anemia may correlate with adverse events, poor quality of life (QoL), decreased adjuvant chemotherapy (ACT) dose intensity, shorter relapse-free survival (RFS) or overall survival (OS). METHODS: The JBR.10 trial demonstrated significantly longer survival with adjuvant cisplatin and vinorelbine (n=242) compared to observation (n=240) in patients with resected NSCLC [Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005;352(25):2640-2]. This exploratory analysis evaluates the predictive value of baseline (in all patients) and during-treatment (in ACT arm only) hemoglobin (Hb) levels on OS and RFS when adjusted for prognostic factors. Baseline (in all patients) and during treatment (in ACT arm only) Hb levels were also correlated with adverse events, QoL, morbidity and ACT dose intensity. RESULTS: Baseline Hb did not predict RFS or OS. However, there was a trend to shorter OS (p=0.1) when baseline Hb was <120g/L. Lower baseline Hb predicted increased hospitalization (p=0.04) and worse QoL (SOB item, p=0.03) but had no impact on adverse events or dose intensity. There was a trend to longer RFS (p=0.08) in patients with lower nadir during-treatment Hb and to longer OS (p=0.06) and RFS (p=0.08) in patients with maximum during-treatment Hb drop >30% that was not maintained when ACT dose intensity was included in the model. Maximum during-treatment Hb drop >30% correlated with increased lethargy (p=0.003) and worse QoL (fatigue item, p=0.07). CONCLUSIONS: Lower baseline and during-treatment Hb levels seem associated with poorer QoL, fatigue and increased hospitalization. There is a trend for shorter OS in patients with lower baseline Hb levels.

Mediastinal tumour in a pregnant patient presenting as acute cardiorespiratory compromise.

A parturient at 35 weeks' gestation presented with severe shortness of breath, orthopnea and signs of fetal compromise. She was diagnosed with a large mediastinal tumour occupying 65% of transthoracic diameter, and a pericardial effusion. The trachea, both mainstem bronchi, pulmonary artery and superior vena cava were compressed. Her dyspnea continued despite relief of the cardiac tamponade by percutaneous drainage. Tissue obtained via anterior mediastinotomy, performed under local anesthesia infiltration, revealed a definitive diagnosis of non-Hodgkin's lymphoma. The patient improved symptomatically following initiation of steroids and chemotherapy. She was delivered by elective cesarean section under epidural anesthesia on the fifth day after starting chemotherapy. The postoperative course was complicated by the development of a large pleural effusion that required drainage. Mother and baby were well at three and six-month follow up oncology visits.

Relation of the static compliance curve and positive end-expiratory pressure to oxygenation during one-lung ventilation.

BACKGROUND: Positive end-expiratory pressure (PEEP) is commonly applied to the ventilated lung to try to improve oxygenation during one-lung ventilation but is an unreliable therapy and occasionally causes arterial oxygen partial pressure (PaO(2)) to decrease further. The current study examined whether the effects of PEEP on oxygenation depend on the static compliance curve of the lung to which it is applied. METHODS: Forty-two adults undergoing thoracic surgery were studied during stable, open-chest, one-lung ventilation. Arterial blood gases were measured during two-lung ventilation and one-lung ventilation before, during, and after the application of 5 cm H(2)O PEEP to the ventilated lung. The plateau end-expiratory pressure and static compliance curve of the ventilated lung were measured with and without applied PEEP, and the lower inflection point was determined from the compliance curve. RESULTS: Mean (+/- SD) PaO(2) values, with a fraction of inspired oxygen of 1.0, were not different during one-lung ventilation before (192 +/- 91 mmHg), during (190 +/- 90), or after ( 205 +/- 79) the addition of 5 cm H(2)O PEEP. The mean plateau end-expiratory pressure increased from 4.2 to 6.8 cm H(2)O with the application of 5 cm H(2)O PEEP and decreased to 4.5 cm H(2)O when 5 cm H(2)O PEEP was removed. Six patients showed a clinically useful (> 20%) increase in PaO(2) with 5 cm H(2)O PEEP, and nine patients had a greater than 20% decrease in PaO(2). The change in PaO(2) with the application of 5 cm H(2)O PEEP correlated in an inverse fashion with the change in the gradient between the end-expiratory pressure and the pressure at the lower inflection point (r = 0.76). The subgroup of patients with a PaO(2) during two-lung ventilation that was less than the mean (365 mmHg) and an end-expiratory pressure during one-lung ventilation without applied PEEP less than the mean were more likely to have an increase in PaO(2) when 5 cm H(2)O PEEP was applied. CONCLUSIONS: The effects of the application of external 5 cm H(2)O PEEP on oxygenation during one-lung ventilation correspond to individual changes in the relation between the plateau end-expiratory pressure and the inflection point of the static compliance curve. When the application of PEEP causes the end-expiratory pressure to increase from a low level toward the inflection point, oxygenation is likely to improve. Conversely, if the addition of PEEP causes an increased inflation of the ventilated lung that raises the equilibrium end-expiratory pressure beyond the inflection point, oxygenation is likely to deteriorate.

Induction chemoradiation and surgical resection for non-small cell lung carcinomas of the superior sulcus: Initial results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160).

OBJECTIVE: The rate of complete resection (50%) and the 5-year survival (30%) for non-small cell lung carcinomas of the superior sulcus have not changed for 40 years. Recently, combined modality therapy has improved outcome in other subsets of locally advanced non-small cell lung carcinoma. This trial tested the feasibility of induction chemoradiation and surgical resection in non-small cell lung carcinoma of the superior sulcus with the ultimate aim of improving resectability and survival. METHODS: Patients with mediastinoscopy-negative T3-4 N0-1 superior sulcus non-small cell lung carcinoma received 2 cycles of cisplatin and etoposide chemotherapy concurrent with 45 Gy of radiation. Patients with stable or responding disease underwent thoracotomy 3 to 5 weeks later. All patients received 2 more cycles of chemotherapy and were followed up by serial radiographs and scans. Survival was calculated by the Kaplan-Meier method and prognostic factors were assessed for significance by Cox regression analysis. RESULTS: From April 1995 to September 1999, 111 eligible patients (77 men, 34 women) were entered in the study, including 80 (72.1%) with T3 and 31 with T4 tumors. Induction therapy was completed as planned in 102 (92%) patients. There were 3 treatment-related deaths (2.7%). Cytopenia was the main grade 3 to 4 toxicity. Of 95 patients eligible for surgery, 83 underwent thoracotomy, 2 (2.4%) died postoperatively, and 76 (92%) had a complete resection. Fifty-four (65%) thoracotomy specimens showed either a pathologic complete response or minimal microscopic disease. The 2-year survival was 55% for all eligible patients and 70% for patients who had a complete resection. To date, survival is not significantly influenced by patient sex, T status, or pathologic response. CONCLUSIONS: (1) This combined modality treatment is feasible in a multi-institutional setting; (2) the pathologic complete response rates were high; and (3) resectability and overall survival were improved compared with historical experience, especially for T4 tumors, which usually have a grim prognosis.

Infection with Burkholderia cepacia in cystic fibrosis: outcome following lung transplantation.

As a result of concern over excessive mortality after lung transplantation, many transplant programs refuse to accept cystic fibrosis (CF) patients infected with Burkholderia cepacia. As a significant proportion of patients with CF in our community are infected with this organism, we have continued to provide lung transplantation as an option. A retrospective review was conducted of medical records of all patients with CF transplanted between March 1988 and September 1996. Fifty-six transplant procedures were performed in 53 recipients with CF between March 1988 and September 1996. Twenty-eight had B. cepacia isolated pretransplant and 25 remaining positive post-transplant. Of the 53 recipients, 19 have died (15 of 28 [54%] B. cepacia positive and 4 of 25 [16%] B. cepacia negative). B. cepacia was responsible for or involved in 14 deaths. Nine of the deaths occurred in the first 3 mo post-transplantation. One-year survival was 67% for B. cepacia positive patients and 92% for B. cepacia negative patients. Recent modifications in antimicrobial and immunosuppressive therapy since 1995 have resulted in no deaths early post-transplant in the last five patients transplanted. We conclude that early mortality in patients with CF infected with B. cepacia is significantly higher than in those not infected with B. cepacia. Modifications in post-transplant medical therapy may improve outcome.

Surgeons' assessment of symptoms suggesting extrathoracic metastases in patients with lung cancer. Canadian Lung Oncology Group.

BACKGROUND: In patients with apparently operable non-small cell lung cancer (NSCLC), clinicians often omit investigation for M disease in asymptomatic patients. Previous investigations have not specified in detail what is meant by "symptomatic," and this could differ between surgeons. We have investigated the extent to which surgeons' criteria differ for presence of symptoms. METHODS: Participating surgeons from seven centers, enrolled patients they judged "asymptomatic" in a randomized trial of investigational strategies for NSCLC. Patients completed a structured questionnaire describing symptoms of the central nervous system (CNS). In 685 patients, we documented CNS symptom recurrence after resectional surgery over 1 year of follow-up. RESULTS: Two centers enrolled only patients without even the mildest symptoms. Three centers took an intermediate approach, occasionally classifying patients with mild symptoms as "asymptomatic" and thus enrolling them in the trial. Two centers classified an appreciable number of patients with minimal symptoms, and occasionally with more than minimal symptoms, as "asymptomatic." Patients with even mild CNS symptoms were more likely to subsequently present with CNS metastases. CONCLUSIONS: Thoracic surgeons differ in their ideas of what may constitute the symptoms of M disease. Patients with structured questionnaire results that suggest symptoms of CNS disease are more likely to have CNS symptom recurrence after resectional surgery.

Correlation of chest radiographic findings with biopsy-proven acute lung rejection.

The purpose of this study was to determine the chest radiographic findings of acute rejection and the accuracy of chest radiography in making this diagnosis in patients undergoing lung transplantation. For each of 100 transbronchial biopsies performed on 25 lung transplant recipients (single lung in three, double lung in 22), chest radiographs obtained within 24 hours before the biopsy were reviewed retrospectively without knowledge of clinical or biopsy information. Transbronchial biopsy revealed 42 instances of acute rejection in 17 patients and 58 instances of no acute rejection (normal, n = 43; other processes, n = 15). All pulmonary parenchymal radiographic abnormalities were assessed. Acute rejection was associated with the presence of middle or lower lung reticular interstitial or airspace disease in 21 lungs (sensitivity = 0.50 [21/42]). This pattern was seen in 18 lungs without acute rejection (specificity = 0.69 [40/58]). There was no difference in the appearance of the lungs between grades 1 and 2 acute rejection. Normal lungs were noted in 20 instances of acute rejection (48%). The authors conclude that chest radiograph findings are abnormal in about 50% of instances of biopsy-proven acute rejection. Because the appearance of acute rejection is similar to that of other conditions, the diagnosis cannot be made accurately by chest radiography.

Cytomegalovirus viremia in lung transplant recipients receiving ganciclovir and immune globulin.

BACKGROUND: Cytomegalovirus (CMV) disease is an important cause of organ transplant-related morbidity and mortality. During the last 5 years at our institution, prophylactic ganciclovir and hyperimmune globulin have been routinely administered to lung transplant recipients whenever the donor or the recipient was CMV antibody-positive. We sought to assess the efficacy of prophylaxis on viremia, CMV disease, and bronchiolitis obliterans syndrome (BOS). METHODS: A retrospective chart review of 61 consecutive lung transplants performed between recipients between January 1993 and August 1995 was performed. Fifty-six patients who survived at least 1 month were analyzed. Patients were considered at risk for CMV disease whenever pretransplant donor or recipient serology was positive. RESULTS: Fourteen of the 39 patients at risk (36%) had viremia while on prophylaxis. The rate of CMV disease was 13% during the first 6 months following transplantation. A donor whose CMV serology was positive appeared to increase the risk of BOS in a Cox regression model (relative risk=2.4; 95% confidence interval=0.86-6.74; p=0.0957). Neither age, CMV infection (viremia or a positive specimen from BAL), recipient's serology at the time of transplantation, or CMV disease was associated with BOS. None of these variables was associated with mortality on Cox regression analysis or univariate analysis. CONCLUSIONS: Administration of combination ganciclovir and hyperimmune globulin prophylactic therapy to lung transplant recipients at risk for CMV infection and disease is associated with a relatively low incidence of disease, which appears only after prophylaxis treatment with ganciclovir is completed. Ganciclovir prophylaxis does not prevent CMV viremia; however, viremia while on prophylaxis is not predictive of disease.

Reperfusion edema after lung transplantation: radiographic manifestations.

PURPOSE: To characterize the radiographic manifestations of reperfusion edema after lung transplantation and to correlate the severity of the radiographic findings with pulmonary physiology. MATERIALS AND METHODS: Chest radiographs obtained after 45 lung transplantation procedures (20 single, 25 double) were reviewed retrospectively. Physiologic parameters (alveolar-arterial gradient, ratio of partial pressure of oxygen to fraction of inspired oxygen) were noted in patients who underwent intubation. RESULTS: Reperfusion edema appeared on day 1 in 39 transplants and by day 3 in 44. One patient's lungs remained clear. Peak severity occurred by day 4 in 43 of 44 transplants. At peak severity, reperfusion edema appeared as reticular interstitial disease in the upper (19%), middle (33%), and lower (34%) lung zones or air-space disease in the upper (31%), middle (61%), and lower (57%) zones. Reperfusion edema was asymmetric after double-lung transplantation in nine patients. The process cleared by day 10 in five transplants and by day 21 in another seven. There was a poor correlation between the severity of radiographic findings and physiologic measurements. CONCLUSION: Reperfusion edema is almost invariable after lung transplantation and most often appears as air-space disease in the middle and/or lower lung zones. The severity of radiographic findings is a poor indicator of pulmonary physiology.

Status of lung transplant recipients surviving beyond five years.

BACKGROUND: Prolonged survival after lung transplantation is now commonplace as a result of advances in surgical techniques and postoperative management protocols. Although 1- and 5-year functional and survival data after lung transplantation are well known, sparse information is available regarding functional status of recipients surviving beyond 5 years. METHODS: The medical records and pulmonary function study results of lung transplant recipients who had survived at least 5 years as of September 1995 were retrospectively reviewed. RESULTS: Of the 76 transplantations performed between November 1983 and September 1990, 30 (39.5%) were double lung transplantations, and 46 (60.5%) were single lung transplantations. Thirty-one recipients were alive 5 years after transplantation (12 double lung transplantations, 19 single lung transplantations). The 5-, 6-, and 7-year survival rates were 44%, 34%, and 29%, respectively. There was no association or difference in cytomegalovirus status, sex, and blood group between those who died within 5 years and those who survived beyond 5 years. The median percent predicted FEVs for single and double lung transplant recipients were as follows: 5 yrs-75%, 75%; 6 years-73%, 75%; 7 years-68%, 73%. The proportion of recipients with bronchiolitis obliterans syndrome according to published criteria was as follows: stage 0, 32%; stage I, 19%; stage II, 16%; and stage III, 19%. The functional status (i.e., active, working, disabled) 5 years after transplantation was as follows: active/working, 74%; active but not working, 13%; some limitation/independent, 10%; and disabled, 3%. CONCLUSION: Bronchiolitis obliterans syndrome is a frequent occurrence in long-term survivors. Nevertheless, in spite of this condition, most recipients have acceptable lung function, are active, and are generally working.

Simultaneous single-lung transplantation and lung volume reduction.

We report our experience with 2 cases of simultaneous single-lung transplantation and lung volume reduction for emphysema. The lung volume reduction was undertaken electively in an attempt to improve overall lung function above that to be expected from single-lung transplantation alone. There were no postoperative problems related to the addition of lung volume reduction. The pulmonary function at 3 months was greater than that seen in a retrospective group of bilateral lung transplants previously reported from our institution.

Adenoid cystic carcinoma of the airway: thirty-two-year experience.

METHODS: We have reviewed our experience in 38 patients with adenoid cystic carcinoma of the upper airway seen between 1963 and 1995. The mean age was 44.8 years (15 to 80 years) with a male/female ratio of 1:1.1. Thirty-two of the 38 patients were treated by resection and reconstruction (primary anastomosis 28; Marlex mesh prosthesis 4). Twenty-six of the 32 patients undergoing resection received adjuvant radiotherapy. Six patients with unresectable tumors were treated primarily with radiotherapy only. RESULTS: Pathologic examination revealed local invasion beyond the wall of the trachea in all patients. In a majority, microscopic extension was found in submucosal and perineural lymphatics, well beyond the grossly visible or palpable limits of the tumor. Lymphatic metastases were relatively uncommon, occurring in only five of 32 (19%) patients undergoing resection. Metachronous hematogenous metastases occurred in 17 of 38 patients (44%). Thirteen of these 38 patients (33%) had pulmonary metastases. Sixteen of 32 resections were complete and potentially curative. There were two deaths within 30 days of operation. The mean survival in the 14 patients undergoing complete resection was 9.8 years (12 months to 29 years). Sixteen of 32 resections were incomplete (residual tumor at the airway margin on final pathologic examination), with one operative death occurring in this group. The mean survival in the 15 surviving patients was 7.5 years (4 months to 21 years). Six patients were treated with primary radiation only and had a mean survival of 6.2 years (2 months to 14.3 years). In the patients with pulmonary metastases, mean survival was 37 months (4 months to 7 years) from the time of diagnosis of the pulmonary metastasis until their death. CONCLUSION: Adenoid cystic carcinoma of the upper airway is a rare tumor, which is locally invasive and frequently amenable to resection. Although late local recurrence after resection is a feature of this tumor (up to 29 years), excellent long-term palliation is commonly achieved after both complete and incomplete resection. There was a small difference in survival between patients having complete and incomplete resection. Long periods of control can be obtained with radiotherapy alone. The best results, in this series of patients, were obtained by resection. Adjuvant radiotherapy is assumed to favorably influence survival.

Quality of life following transplantation of the heart, liver, and lungs.

The purpose of this study was to describe the quality of life of patients who have received a transplant of the heart, liver, and lungs. We wished to document how the different patient groups fared in relation to each other with respect to physical, psychological, and social functioning, as well as in relation to published normative data. We also wished to identify factors that contribute to better functioning. We sent out a questionnaire by mail and received responses from 55 heart, 149 liver, and 59 lung transplant recipients (82% response rate). Measures included the SF-36, Mental Health Inventory, the State Anxiety Inventory, the UCLA Loneliness Scale-Revised, a quality of life measure that rated degree of improvement since transplantation, a measure of degree of difficulty in following medical and lifestyle regimens, sleep disturbance, and the Illness Intrusiveness Rating Scale. Results indicated that lung transplant patients reported better functioning than heart or liver transplant patients in all three domains of physical, psychological, and social functioning. Lung patients' level of functioning was equivalent to or better than published norms for the SF-36. Heart and liver recipients reported equivalent functioning to published norms in some domains, but reported impairment in the areas of physical and social functioning. Heart patients especially reported greater intrusiveness of their illness on their daily lives and indicated more difficulty complying with their lifestyle regimen. In all three groups, a large majority of patients reported feeling that life had improved since transplant with respect to health, energy level, activity level, and overall quality of life. Fewer patients reported improvements in the areas of sex life, marriage, family relationships, and social relationships. Where there were differences among the three patient groups, again it was the lung patients who reported more improvement in life since transplantation. Patients with better physical functioning tended to have more energy and pep, to be younger, to see themselves as being in better health, to feel less intrusion on their lives of their illness, and to be employed. Those with better psychological functioning tended to report less sleep disturbance, less loneliness, better social functioning, more vitality, and to be older. Better social functioning was associated with better mental health, less illness intrusiveness, and less role impairment as a result of physical or emotional factors. Relatively few patients-roughly a quarter of the total sample-reported that they were working either full or part time. We conclude that transplantation results in improved quality of life overall, but that problems persist for some patients in their physical and social functioning. Interventions aimed at improving rehabilitation in specific targeted areas may enable patients to resume a more fulfilling lifestyle posttransplant.

Bronchiolitis obliterans organizing pneumonia (BOOP) in lung transplant recipients.

We reviewed all tissue specimens from 163 transplant patients (108 double lung transplant [DLT], 55 single lung transplant [SLT]) between November 1983 and January 1994 for abnormalities indicating bronchiolitis obliterans organizing pneumonia (BOOP) and found 17 cases (14 DLT and 3 SLT). Of the three SLTs, BOOP was diagnosed by open lung biopsy (OLB) in two and one was found at autopsy. Of the 14 DLTs, BOOP was diagnosed by transbronchial biopsy (TBB) specimens (9), OLB specimens (2), autopsy (1), TBB and OLB specimens (1), and OLB specimens and autopsy (1). BOOP was found between 1 and 43 months posttransplantation; time of survival from diagnosis was between 2 and 36 months with 9 patients presently alive. Concurrent pathologic diagnosis at the time of BOOP findings were as follows: acute rejection (7) (grade 1 [4] and grade 2 [3]), BO and grade 1 rejection (2), BO and grade 2 rejection (2), BO and Aspergillus infection (1), acute alveolar injury (1), acute alveolar injury and pulmonary embolus (1), acute rejection (grade 1) and Burkholderia cepacia pneumonia (1). No other pathologic diagnosis was found in 1 patient. In total, 11 of 17 patients (65%) had associated acute rejection. Of the 17 patients, 7 subsequently developed BO and 3 had BO before the finding of BOOP. Death occurred in 8 patients (5 DLT and the 3 SLT) between 2 and 6 months after the diagnosis. We conclude that BOOP is an important complication after lung transplantation; it was present in 13% of DLTs and 5% of SLTs. BOOP was most often associated with acute rejection.

Methotrexate can halt the progression of bronchiolitis obliterans syndrome in lung transplant recipients.

BACKGROUND: Methotrexate has been used successfully to treat refractory or recurrent rejection in heart transplant recipients. We therefore conducted an open pilot study to determine whether methotrexate is useful in the treatment of chronic rejection after lung transplantation. METHODS: Between December 1993 and January 1995 methotrexate was prescribed to 10 patients with persistent or progressive bronchiolitis obliterans despite multiple attempts to control the chronic rejection with conventional treatment (pulse steroids or antilymphocyte products, or both). Data from the nine patients with a minimum of 6 months of follow-up were collected. RESULTS: No patients have died. The spirometry data of the eight patients with declining values of forced expiratory volume in 1 second are presented. Before initiation of methotrexate therapy the median decline in forced expiratory volume in 1 second was 1.4 +/- 0.8 L, or 43% +/- 17%, from the highest preinterventional forced expiratory volume in 1 second value during the preceding 12 months. At 6 months the median decline in forced expiratory volume in 1 second from the time methotrexate therapy was started was 0.1 +/- 0.2 L, or 3% +/- 11%. At 9 months (n = 6) the value was 0.2 +/- 0.2 L, or 6% +/- 12%. At 12 months (n = 5) the median decline was 0.4 +/- 0.3 L, or 9% +/- 16%. In two patients there has been no further decline in forced expiratory volume in 1 second since methotrexate therapy was started (one patient has had a slight but sustained improvement). Five patients have had a reduction in forced expiratory volume in 1 second of 10% or less at most recent follow-up, and only one patient has derived no apparent benefit from methotrexate therapy. Toxicity has been minimal. CONCLUSIONS: Methotrexate is a potentially promising therapeutic alternative in the therapy of bronchiolitis obliterans syndrome in lung transplant recipients.

An intracardiac mass presenting as atrial fibrillation in a patient with testicular carcinoma.

A 20-year-old male with known testicular carcinoma presented with atrial fibrillation. Investigations, which revealed a pulmonary metastasis with invasion of the left atrium, are presented along with a review of the current literature.