Daniele Bendayan

Peripheral Arterial Stiffness and Endothelial Dysfunction in Idiopathic and Scleroderma Associated Pulmonary Arterial Hypertension

Objective. Pulmonary endothelial dysfunction and increased reflection of pulmonary pressure waves have been reported in pulmonary arterial hypertension (PAH). However, the systemic vascular involvement is not fully understood. Our study focused on the systemic arterial stiffness and endothelial involvement in idiopathic and scleroderma associated PAH. Methods. Peripheral arterial stiffness and endothelial function were evaluated in 38 patients with idiopathic (n = 28) and scleroderma associated (n = 10) PAH, and 21 control subjects (13 healthy; 8 with scleroderma and normal pulmonary pressure). All participants underwent clinical and cardiopulmonary evaluation. Arterial stiffness was measured through the fingertip tonometry derived augmentation index (AI), which is the boost increase in the late systolic pressure wave after the initial systolic shoulder. Endothelial function was measured by forearm blood flow dilatation response to brachial artery occlusion by a noninvasive plethysmograph (EndoPAT 2000), which is associated with nitric oxide-dependent vasodilatation and yields a peripheral arterial tone (PAT) ratio. Results. Mean systolic pulmonary pressure was 70.5 ± 21.6 mm Hg (idiopathic-PAH) and 69.3 ± 20 mm Hg (scleroderma-PAH). AI was higher in scleroderma patients (10.5% ± 19.6% in healthy controls, 9.0% ± 21.5% in idiopathic-PAH, 20.1% ± 19.1% in scleroderma-PAH, and 24.4% ± 18.9% in scleroderma-controls; nonsignificant). PAT ratio was significantly lower (p < 0.05) than control values in idiopathic-PAH and scleroderma-PAH (PAT ratio: control 2.20 ± 0.25; idiopathic 1.84 ± 0.51; scleroderma 1.66 ± 0.66). AI was not correlated to endothelial dysfunction. There were no differences between the 2 PAH patient groups in age, body mass index, New York Heart Association classification, or 6-min walk test. Conclusion. Our study shows a trend towards increased arterial stiffness in scleroderma (nonsignificant), and also peripheral endothelial dysfunction in idiopathic-PAH and in scleroderma-PAH. These findings suggest involvement of different vessels in scleroderma-PAH compared to idiopathic-PAH.

Development of malignancy following lung transplantation

Background. A substantial excess risk of certain malignancies has been demonstrated after organ transplantation. Immunosupressive treatment to prevent allograft rejection is probably the main cause. Methods. We reviewed retrospectively all medical records of the 121 patients that underwent lung and heart-lung transplantation from 1992 until December 2004. We compared our results to the International Society for Heart and Lung Transplantation (ISHLT) registry data and previous reports concerning lung transplantation. Results. 102 of the 121 patients survived for 3 months to 12 years. Malignancies developed in 16 patients, as follows: lymphoproliferative disorder in 3, Kaposis sarcoma in 3, other nonmelanoma skin cancers in 7, urinary bladder transitional cel carcinoma in 3, and colon cancer in 1. Patients with malignancy were older at transplantation than those without (mean ± SD, 54.1±7.8 vs. 49.5±14.2 years; P=0.03). Fourteen had smoked in the past. Four died of bronchiolitis obliterans. In comparison with the ISHLT, we observed more skin cancer and transitional cell carcinoma (12.8% vs. 0.7% and 3.8% vs. 0.03%, respectively) and a similar frequency of posttransplant lymphoproliferative disease. Conclusions. We conclude that malignancy is a common complication after lung transplantation. In Israel, which is sunny most of the year, skin cancers and transitional cell carcinoma of bladder are more common. Modification of the immunosuppression late posttransplantation may reduce the risk of cancer. Patients should also be counseled to avoid sun exposure and ensure adequate hydration.

Combination therapy with prostacyclin and tadalafil for severe pulmonary arterial hypertension: a pilot study.

Abstract:  Despite the introduction of new drugs that have changed the course of pulmonary arterial hypertension (PAH), some patients are still refractory to treatment and deteriorate rapidly. Long‐acting phosphodiesterase‐5 inhibitors are a new class of drugs that are effective in PAH. This prospective study assessed the potential of combination therapy with prostacyclin and tadalafil for treatment of severe PAH. We report four cases of severe PAH that deteriorated despite prostacyclin therapy. Two patients had Eisenmenger syndrome, one had pulmonary hypertension associated with scleroderma and one had histiocytosis X. All were treated with tadalafil, 10–20 mg once daily, in addition to prostacyclin. After 3 months of treatment, all patients improved clinically, with an increase in mean 6MWD from 214 to 272 m. In three patients, the New York Heart Association functional class decreased from IV to III. Echocardiograms showed no significant changes in pulmonary arterial pressure. Although this study was limited by the small sample size, it suggests that tadalafil in combination with prostacyclin is an effective treatment for severe PAH. Tadalafil may be beneficial for the treatment of patients with advanced disease.

The anti-cyclic citrullinated peptide response in tuberculosis patients is not citrulline-dependent and sensitive to treatment.

IntroductionPatients with tuberculosis (TB) frequently produce anti-citrullinated protein antibodies (ACPA). The objective of this study is to characterize the citrulline-dependence of the ACPA reactivity in sera of patients with mycobacterium infections.MethodsSerum samples of 134 patients with untreated mycobacterium infections (122 TB, 12 nontuberculous mycobacterium) were tested for antibodies against both the citrullinated (Cit) and the non-citrullinated (Arg) form of 2 cyclic synthetic peptides. In 33 patients, a follow-up sample was tested six months after starting anti-mycobacterial drugs.ResultsA substantial proportion of patients with mycobacterial infections demonstrated antibodies against 0401Cit, 0401Arg, 0722Cit and 0722Arg. Fourteen patients demonstrated anti-0401Cit, 83 anti-0401Arg, 22 anti-0722Cit and 61 anti-0722Arg, while none of these antibodies were detected in the 20 healthy controls. All the patients but one, who were anti-0401Cit and anti-0722Cit positive, demonstrated reactivity against the respective Arg peptide. In the subset of 33 patients with a follow-up test six months after starting treatment, the mean levels of antibodies to 0401Cit, 0401Arg, 0722Cit and 0722Arg significantly decreased after treatment. All the patients who were anti-0401Cit and anti-0722Cit positive turned negative after treatment. The presence of anti-0401Cit/Arg and anti-0722Cit/Arg was found to be significantly correlated with the presence of HIV.ConclusionsACPA may be found in patients with TB. In most of the cases, the reactivity is citrulline independent. A positive cyclic citrullinated peptide (CCP) test in these patients should therefore be interpreted with care, and preferably followed by a control ELISA with a non-citrullinated antigen.

Successful lung transplantation for talcosis secondary to intravenous abuse of oral drug

Talcosis due to intravenous injection of oral drugs can cause severe pulmonary disease with progressive dyspnea even when drug use is discontinued. We describe a 54-year-old woman with severe emphysema who underwent left lung transplantation. The patient had a remote history of intravenous injection of crushed methylphenidate (Ritalin) tablets. Chest computed tomography showed severe emphysematous changes, more prominent in the lower lobes. Microscopic examination of the extracted lung demonstrated multinucleated giant cells with birefringent crystals, compatible with talcosis. At follow-up, daily symptoms were completely alleviated and lung function was good. We recommend that lung transplantation be considered as a viable option in the treatment of talcosis.

Osteolytic Lesions as a Presenting Sign of Acute Nonlymphocytic Leukemia

Osteolytic lesions occur rarely in acute leukemia, especially in adults. We describe a patient with chronic myelomonocytic leukemia, in whom multiple osteolytic lesions were the presenting sign of the transformation into acute leukemia. Local irradiation to a painful lesion in the left hip resulted in transient but significant symptomatic relief with improved quality of life. We conclude that osteolytic lesions, although rare in adult acute leukemia, indicate an advanced disease state, but may respond to palliative local irradiation.