Reliability of parameters during stair ascent measured with Leonardo Mechanograph(®) Stair A in healthy subjects.

OBJECTIVES: Stair climbing (SC) as daily activity is assessed with different SC-tests, but none directly measures ground reaction force over several steps. The Leonardo Mechanograph Stair A has five steps and four force sensors. This study aimed at investigating the reliability of the Stair A test for force, power and time to SC. METHODS: 55 healthy participants (age: 48±14 years) were five times tested during SC with self-chosen and fast speed. 30 participants were examined for test-retest-reliability, calculated with the intraclass correlation coefficient (ICC). The variability was examined with the coefficient of variation (CV). To determine potential associations between SC and jumping performance or daily activity, squat and countermovement jumps were additionally performed and the International physical activity questionnaire (IPAQ) was completed. RESULTS: The inter-visit ICCs of self-chosen and fast SC were good to excellent 0.63-0.77. The intra-visit ICCs were excellent after three trials (0.78-0.88). The CVs for SC with self-chosen speed were lower (2.1-6.6%) than those for fast SC (4.9-10.8%). There were no significant correlations between SC and jump parameters and only moderate correlations with the IPAQ. CONCLUSION: The Stair A is a reliable tool for the assessment of SC.

Sweet's syndrome involoving the musculoskeletal system during treatment of promyelocytic leukemia with all-trans retinoic acid.

Induction therapy of promyelocytic leukemia with all-trans retinoic acid is a standard therapy despite significant side-effects. The most important, the "retinoic acid syndrome", consists of a hyperinflammatory reaction with capillary leakage (edema, pleural, and pericardial effusion), infiltration of myeloid cells into internal organs and systemic signs of inflammation. We describe here two cases of another hyperinflammatory reaction during all-trans retinoic acid therapy, the Sweet's syndrome, consisting of infiltrates of the skin and internal organs by neutrophilic granulocytes. Fever, painful erythematous cutaneous plaques, prominent musculoskeletal involvement (myositis, fasciitis), a sterile pulmonary infiltration and intercurrent proteinuria characterized the clinical course of all-trans retinoic acid-associated Sweet's syndrome. Treatment with glucocorticoids led to resolution of the syndrome within 48 h. Three other cases of all-trans retinoic acid-associated Sweet's syndrome without involvement of internal organs, prominent on our cases, were published previously. Recognition of ATRA-associated Sweet's syndrome is of practical importance.

Lupus erythematosus and Miller-Fisher syndrome.

OBJECTIVE: To compare the clinical course of an unusual case of Miller-Fisher syndrome in systemic lupus erythematosus with therapeutic interventions, in particular with plasma exchanges. DESIGN: The clinical state and laboratory and electrophysiologic parameters were controlled for over a year and related to therapeutic attempts with immunoglobulins, steroids, and plasma exchanges. SETTING: Medical intensive care unit of a university hospital. PATIENT: A 17-year-old black female student with known systemic lupus erythematosus who developed ataxia, are flexia, and ophthalmoplegia (Miller-Fisher syndrome) and later became tetraplegic and required full mechanical ventilatory support. RESULTS: High-dose immunoglobulin treatment combined with corticosteroid pulse therapy was not beneficial. However, plasma exchange (performed five times over a period of 4 months) was followed by a striking clinical improvement within hours after each plasma exchange. CONCLUSIONS: Plasma exchange appears to remove a yet unknown agent producing a distal motor nerve conduction block and is efficacious in severe neuropathy associated with Miller-Fisher syndrome in lupus erythematosus.

Shortcomings of chest radiography in detecting Pneumocystis carinii pneumonia.

The radiographic presentation of Pneumocystis carinii pneumonia (PCP) was studied in 93 consecutive patients to determine the frequency of normal findings on chest roentgenograms and possible correlations with clinical or laboratory findings. The roentgenograms were reviewed by two radiologists in an independent, blinded way and judged with a score distinguishing between none, interstitial, and acinar infiltrates. Discordance mainly between absent versus interstitial and interstitial versus acinar infiltrates occurred in 23% of roentgenograms and was settled by consensus. The majority of patients presented with moderate-to-mild symptoms; the combination of dyspnea, cough, and fever was present in 53%. Lactate dehydrogenase (LDH) was elevated in 63%, hypoxemia (PaO2 < 75 mm Hg) was present in 57%. Findings on chest roentgenograms were normal in 39%, whereas 36% showed interstitial and 25% acinar infiltrates. These three radiographic groups represented an increasingly severe PCP, indicated by higher LDH levels and hypoxemia (both p < 0.05). In a multivariate logistic regression, normal roentgenograms were predicted by low LDH and low peripheral blood granulocytes (p < 0.005). Mortality within 3 weeks was only 4% and correlated with the severity of infiltrates (p < 0.05). Normal roentgenograms thus corresponded to an oligosymptomatic, less severe PCP. In immunodeficient HIV-infected patients, a normal chest roentgenogram does not exclude PCP and should not distract from attaining a definite diagnosis by examination of induced sputum or bronchoalveolar lavage.

Salvage therapy with mycophenolate mofetil for lung transplant bronchiolitis obliterans: importance of dosage.

BACKGROUND: Bronchiolitis obliterans (BO) is the most important long-term complication of lung transplantation. Treatment of this condition is often unsuccessful. METHODS: A patient presented with early BO. Despite OKT3 and the addition of methotrexate, the patient needed persistently high doses of prednisone to maintain lung function at a moderate level. Only the substitution of azathioprine by mycophenolate mofetil (MMF, 3 g/day) made it possible to reduce the dose of prednisone. RESULTS: Reduction of the dose of MMF to 2 g/day resulted in a deterioration of lung function, which improved impressively after MMF was increased again to 3 g/day. CONCLUSIONS: MMF may be a valuable therapy for lung transplant BO. However, the use of a high dose, i.e., 3 g/day, may be crucial.

Efficacy and cost effectiveness of oral ganciclovir in the prevention of cytomegalovirus disease after lung transplantation.

BACKGROUND: Cytomegalovirus is the single most frequent pulmonary pathogen in lung transplant recipients who survive at least 2 weeks. Patients at increased risk are either seropositive or have received an allograft from a donor with latent infection. Morbidity and mortality caused by cytomegalovirus disease is still considerably high. METHODS: In an open, comparative study, we evaluated the efficacy, tolerance, and cost effectiveness of postoperative ganciclovir prophylaxis: intravenous dose of 2x5 mg/kg/day for 14 days, followed by either intravenous doses of 5 mg/kg]day (five patients), or oral doses of 3x 1000 mg (nine patients) up to 90 days. Oral ganciclovir was continued until prednisone was tapered below 15 mg/day. Prophylaxed groups were compared with a historical control (eight patients) in respect to cytomegalovirus disease, in-hospital stay, overall costs, and survival. Follow-up times and the net state of immunosuppressive therapy between groups were comparable. RESULTS: Six (75%) of the non-prophylaxed patients developed cytomegalovirus disease compared to none in the intravenous and one in the oral ganciclovir group (P=0.013). The non-prophylaxed patients had a longer cytomegalovirus-related in-hospital stay (P=0.018) and nonsignificantly higher cytomegalovirus-related costs. Bronchiolitis obliterans syndrome was less frequent with prophylaxis (P=0.039), and survival tended to be better (P=0.072). The only adverse effect was a subclavian vein thrombosis in the intravenous ganciclovir group. CONCLUSIONS: In lung transplant recipients, ganciclovir prophylaxis, either intravenous or oral, is safe, well tolerated, and effective in preventing cytomegalovirus disease. Moreover, ganciclovir prophylaxis seems likely to reduce the incidence of bronchiolitis obliterans syndrome. The oral formulation might be preferable because its convenience and possibly lower costs.

Extracorporeal photochemotherapy for Epstein-Barr virus-associated lymphoma after lung transplantation.

Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication after transplantation of solid organs. Highest incidence rates have been reported for lung transplant recipients. With the current treatment strategy for early onset PTLD, a reduction of immunosuppressive drugs, mortality of lung transplant recipients with PTLD remains high, due to both, incomplete control of PTLD and transplant rejection. We present a lung transplant recipient with a history of acute rejection and Epstein Barr virus-associated posttransplantation malignant non-Hodgkin's lymphoma. Extracorporeal photochemotherapy, in combination with a moderate reduction of immunosuppressive therapy, resulted in complete disappearance of PTLD. After a first year of follow-up, no further rejection and no recurrence of PTLD have occurred. Treatment with ECP, with its beneficial effects on both, rejection after organ transplantation and malignant lymphoma, may be a particularly valuable approach for the treatment of PTLD in patients after lung transplantation, with its increased risk for transplant rejection.

Osteonecrosis after lung transplantation: cystic fibrosis as a potential risk factor.

BACKGROUND: Osteonecrosis is a known complication after transplantation of solid organs. The incidence of osteonecrosis after lung transplantation is not well documented. METHODS: We investigated the incidence of symptomatic osteonecrosis in lung transplant recipients, transplanted between November 1992 and June 1998 at our institution. For the detection of osteonecrosis, all patients complaining of musculoskeletal pain underwent magnetic resonance imaging. Demographic characteristics, time after transplantation, etiology of underlying lung disease, and the number of steroid pulses for rejection episodes were compared for patients with and without osteonecrosis. RESULTS: Of 63 transplant recipients, all 49 with a follow-up of >3 months were included for analysis. Of seven symptomatic transplant recipients, five cases of osteonecrosis (10%) were detected at a median duration of 216 days (range 44-600) after transplantation. Patients with osteonecrosis have been treated with the same immunosuppressive regimen and with an equal number of steroid pulses for acute rejection episodes (1.4+/-1.1 vs. 1.4+/-1.5, P=0.69), but were younger (26+/-8 vs. 40+/-11 years, P<0.01) than other transplant recipients. Symptomatic osteonecrosis was detected in four of 14 patients (29%) with cystic fibrosis (CF), compared with one osteonecrosis among 35 patients (3%) with other underlying diseases (P<0.02). Within the group of CF patients, specific clinical and demographic characteristics correlating with the risk for subsequent osteonecrosis could not be found. CONCLUSION: In lung transplant recipients, CF may be a risk factor for the development of symptomatic osteonecrosis.

Primary pulmonary hypertension in HIV infection.

A prospective evaluation of 74 human immunodeficiency virus (HIV)-infected patients with cardiopulmonary complaints revealed six patients (8.1 percent) with pulmonary hypertension with elevated right ventricular systolic over right atrial pressure of 58 +/- 8 mm Hg (range, 49 to 66 mm Hg), as documented by Doppler echocardiography. A thromboembolic cause was excluded by normal lung perfusion scans. Electrocardiographic and roentgenographic features of pulmonary hypertension were present in five patients. Two patients died three and nine months after diagnosis of pulmonary hypertension. Autopsy revealed plexogenic pulmonary arteriopathy in both. The observation of six patients with primary pulmonary hypertension (PPH) in a cohort of 1,200 HIV-infected subjects corresponding to an incidence of 0.5 percent is striking and suggests a possible association of PPH with HIV infection.

Diagnostic value of hemosiderin-containing macrophages in bronchoalveolar lavage.

STUDY OBJECTIVE: Our objective was to determine if the hemosiderin content of BAL macrophages allows us to draw any differential diagnostic conclusions in a variety of lung diseases. PATIENTS AND STUDY DESIGN: One hundred one patients who underwent BAL for different diagnostic reasons were studied prospectively. MAIN RESULTS: The highest values for the hemosiderin score (HS) were found in patients with active alveolar hemorrhage and patients who had undergone heart transplantation for congestive heart failure. Compared to a control population, patients with Pneumocystis carinii pneumonia or invasive aspergillosis had a higher HS than patients with bacterial pneumonia or mycobacterial lung infection. High or intermediate values for HS were more often found in patients with a low than in those with a normal platelet count. CONCLUSIONS: The differential diagnostic conclusions which can be based on an HS are limited.

Ventricular fibrillation in a patient with exercise-induced anaphylaxis, normal coronary arteries, and a positive ergonovine test.

Exercise-induced anaphylaxis (EIA) is a rare form of physical allergy. Although histamine release is a feature of EIA, and histamine provocation of coronary spasm has been described, serious cardiac arrhythmias in EIA have not been reported. Exercise-induced anaphylaxis was diagnosed in a survivor of out-of-hospital cardiac arrest due to ventricular fibrillation after ECG signs of coronary spasm. Coronary artery disease was excluded. Ergonovine provocation induced coronary spasm in this patient. This is, to the authors' knowledge, the first description of ventricular fibrillation in EIA, possibly due to coronary spasm.

The role of two-segment bronchoalveolar lavage in the diagnosis of pulmonary infections.

STUDY OBJECTIVE: To determine if performing bronchoalveolar lavage (BAL) from more than one lung segment augments the diagnostic yield in patients with pulmonary infection. PATIENTS AND STUDY DESIGN: Seventy-six patients who underwent bisegmental BAL for the diagnosis or exclusion of pulmonary infection were studied prospectively. MAIN RESULTS: In patients with AIDS, the concentration of Pneumocystis carinii was higher in the upper lobes than in the middle lobes, regardless of whether the patients had been receiving pentamidine prophylaxis. In patients without HIV infection, the number of P carinii clusters was much lower. In 2 of 5 HIV-negative patients, P carinii organisms were detectable but in one of two lavage specimens, whereas in only 1 of 19 AIDS patients, P carinii organisms were not found in both lavaged segments. In bacterial pneumonia, BAL fluid from a segment of the radiologically most involved area had a much higher cell concentration, percentage of neutrophils, and concentration of bacteria than from the segment that was not or less severely involved on chest radiograph. In two of nine patients with AIDS and cytomegalovirus (CMV) pneumonia, cytopathogenic CMV effects were not found in both lavaged segments. In one of eight patients, mycobacteria could be cultured only from one of two radiologically involved segments. CONCLUSION: An increase in the diagnostic sensitivity by performing BAL in two lung segments is limited to cases where P carinii pneumonia is a relevant consideration in immunocompromised patients without HIV infection. In bacterial pneumonia, BAL can be performed in a single radiographically involved lung segment without a loss in diagnostic sensitivity. Since our study population of patients with CMV pneumonitis, mycobacterial infections, and fungal infections was small, no reliable conclusions are possible and BAL of more than one lung segment seems justified until more information is available.

Pulmonary hemorrhage due to inhalation of vapor containing pyromellitic dianhydride.

Pulmonary hemorrhage due to inhalation of fumes or powders containing trimellitic anhydride (TMA) is well known. We report pulmonary hemorrhage in a young man exposed to epoxy resin vapor containing pyromellitic dianhydride (PMDA). Serum IgG antibodies to PMDA could be detected. We conclude that the pulmonary hemorrhage was mediated by a reaction to PMDA in analogy to the TMA-induced disease. We suggest that exposure to any acid anhydride should be considered a possible cause of pulmonary hemorrhage since these compounds share structural and functional similarities.

Prospective evaluation of a prognostic score for Pneumocystis carinii pneumonia in HIV-infected patients.

Serum lactate dehydrogenase levels, alveolar-arterial oxygen gradient, and percentage of neutrophils in bronchoalveolar lavage correlate most strongly with early mortality in Pneumocystis carinii pneumonia (PCP) in HIV-infected patients. However, the individual outcome can not be predicted by these parameters due to a considerable overlap between survivors and nonsurvivors. We prospectively investigated a PCP severity score, which has been developed earlier based on a retrospective analysis. Seven of 94 consecutively examined HIV-infected patients died within 14 days after diagnosis of PCP. A PCP severity score greater than 7 had a positive predictive value for early fatal outcome of 66.7 percent (6/9) and a negative predictive value of 98.8 percent (84/85). The overall diagnostic accuracy was 95.7 percent (90/94). The positive predictive value for early fatal outcome of a P(A-a)O2 > 35 mm Hg was 24 percent (6/25); the negative predictive value was 98.6 percent (68/69). However, the overall diagnostic accuracy was only 78.7 percent (74/94). The PCP severity score is a valuable tool for clinical decision making, for the early identification of patients with a prognostic unfavorable course, and for the comparison of patient populations in future studies of HIV-associated PCP.

Prospective evaluation of a semiquantitative dip slide method compared with quantitative bacterial cultures of BAL fluid.

BACKGROUND: Quantitative bacteriologic workup of BAL fluid (BALF) has evolved as a sensitive and specific technique for the diagnosis of bacterial pneumonia. Conventional quantitative cultures are expensive, time-consuming, and often unavailable on a 24-h basis. Therefore, we evaluated a dip slide method for the semiquantitative measurement of bacterial cultures in BALF specimens and compared the results with those from conventional quantitative cultures. METHODS: Fifty BALF specimens from 45 patients with suspected pulmonary infection were examined prospectively with both methods. We compared the microbiologic results of conventional quantitative cultures with those of the dip slide method that is commercially available for blood cultures. Cost-effectiveness analysis of both methods was performed. RESULTS: In 37 BALF specimens, 64 bacterial strains were detected with both techniques. The dip slide method and conventional cultures showed a high correlation with respect to the colony counts of the individual organisms per milliliter BALF (r=0.935; p= 0.0001) and the sum of colony counts in individual patients (r=0.947; p=0.0001). Although five strains were not detected by the dip slide technique, the diagnostic accuracy was not influenced. In 13 BALF samples, there was no growth of bacteria with both techniques. While the diagnostic yield of both methods was similar, the dip slide technique was 44 to 66% less expensive than conventional cultures. CONCLUSIONS: The examination of BALF with a clip slide method is highly comparable to conventional quantitative culture techniques, less expensive, and can be used independently of a specialized microbiology laboratory on a 24-h basis.

Cavernous destruction of an upper lung lobe in a healthy young man. An unusual roentgenographic presentation of allergic bronchopulmonary aspergillosis.

We describe a 32-year-old man with no history of pulmonary disease who presented with extensive cavernous destruction of the right upper lobe as an incidental finding on a chest x-ray film. All major criteria of allergic bronchopulmonary aspergillosis (ABPA) were present. Histologic examination of the resected lobe showed the typical features of ABPA. The differential diagnosis of multiple cavitating lesions should include ABPA.

The nitric oxide synthase cofactor tetrahydrobiopterin reduces allograft ischemia-reperfusion injury after lung transplantation.

OBJECTIVE: Exogenous nitric oxide reduces ischemia-reperfusion injury after solid organ transplantation. Tetrahydrobiopterin, an essential cofactor for nitric oxide synthases, may restore impaired endothelium-dependent nitric oxide synthesis. We evaluated whether tetrahydrobiopterin administration to the recipient attenuates lung reperfusion injury after transplantation in swine. METHODS: Unilateral left lung transplantation was performed in 15 weight-matched pigs (24-31 kg). Donor lungs were flushed with 1.5 L cold (1 degrees C) low-potassium-dextran solution and preserved for 20 hours. Group I animals served as controls. Group II and III animals were treated with a bolus of tetrahydrobiopterin (20 mg/kg). In addition, in group III a continuous infusion of tetrahydrobiopterin (10 mg/kg per hour over 5 hours) was given. One hour after reperfusion, the recipient right lung was occluded. Cyclic guanosine monophosphate levels were measured in the pulmonary venous and central venous blood. Extravascular lung water index, hemodynamic variables, lipid peroxidation, and neutrophil migration to the allograft were assessed. RESULTS: In group III a significant reduction of extravascular lung water was noted in comparison with the controls (P =.0047). Lipid peroxidation in lung allograft tissue was significantly reduced in group II (P =.0021) and group III ( P =. 0077) in comparison with group I. Pulmonary venous levels of cyclic guanosine monophosphate increased up to 23 +/- 1 pmol/mL at 5 hours in group II and up to 40 +/- 1 pmol/mL in group III (group I, 4.1 +/- 0.5 pmol/mL [I vs III]; P <.001), whereas central venous levels of cyclic guanosine monophosphate were unchanged in all groups. CONCLUSION: Tetrahydrobiopterin administration during lung allograft reperfusion may reduce posttransplantation lung edema and oxygen-derived free radical injury in the graft. This effect is mediated by local enhancement of the nitric oxide/cyclic guanosine monophosphate pathway.

Pulmonary nocardiosis concurrent with Pneumocystis carinii pneumonia in two patients undergoing immunosuppressive therapy.

Two cases with concomitant pulmonary nocardiosis and Pneumocystis carinii pneumonia are described. The first patient developed pneumonia 3 months after heart transplantation while undergoing standard immunosuppressive therapy with cyclosporin, azathioprine and prednisone. The second patient was treated with chemotherapy and subsequent radiotherapy of the mediastinum for a malignant epithelial tumour. He also received prednisone for paraneoplastic dermatomyositis. Chest X-rays of both patients showed a bilateral interstitial pattern and broncho-alveolar lavage revealed P. carinii. Additional dense and localised pulmonary infiltrates led to suspicion of a further infectious agent, namely, Nocardia asteroides, which was isolated from both patients. Since nocardiosis calls for prolonged treatment, extensive diagnostic measures are needed for its early detection.

Complications in the native lung after single lung transplantation.

OBJECTIVES: Single lung transplantation is a viable option for patients with end-stage pulmonary disease; despite encouraging results, we observed serious complications arising in the native lung. We retrospectively reviewed 36 single lung transplants to evaluate the incidence of complications arising in the native lung, their treatment and outcome. METHODS: Between 1991 and 1997, 35 patients received 36 single lung transplants for emphysema (16), pulmonary fibrosis (14), lymphangioleiomyomatosis (4), primary pulmonary hypertension (1) and bronchiolitis obliterans (1). The clinical records were reviewed and the complications related to the native lung were divided into early (up to 6 weeks after the transplant) and late complications. RESULTS: Nineteen complications occurred in 18 patients (50%), leading to death in nine (25%). Early complications (within 6 weeks from the transplant) were bacterial pneumonia (1), overinflation (3), retention of secretions with bronchial obstruction and atelectasis (1), hemothorax (1), pneumothorax (1) and invasive aspergillosis (3); one patient showed active tuberculosis at the time of transplantation. Two patients developed bacterial pneumonia and invasive aspergillosis leading to sepsis and death. The other complications were treated with separate lung ventilation (1), bronchoscopic clearance (1), chest tube drainage (1) and wedge resection and pleurodesis (mechanical) by VATS (1). One patient with hyperinflation of the native lung eventually required pneumonectomy and died of sepsis. The patient with active tuberculosis is alive and well after 9 months of medical treatment. Late complications were recurrent pneumothorax (4), progressive overinflation with functional deterioration (2), aspergillosis (1) and pulmonary nocardiosis (1). Recurrent pneumothorax was treated with chest tube drainage alone (1), thoracoscopic wedge resection and/or pleurodesis (2) and pneumonectomy (1); hyperinflation was treated with thoracoscopic lung volume reduction in both cases; both patients with late infectious complications died. CONCLUSIONS: After single lung transplantation, the native lung can be the source of serious problems. Early and late infectious complications generally result in a fatal outcome; the other complications can be successfully treated in most cases, even if surgery is required.