Samir Nusair

The use of oral pilocarpine in xerostomiaand sjögren's syndrome

OBJECTIVES To analyze the role of oral pilocarpine in the treatment of xerostomia of Sjogrens syndrome (SS). METHODS The medical literature was reviewed for all studies using oral pilocarpine to treat xerostomia caused by SS or radiotherapy registered in the MedLine Silver Platter database from 1966 to 1998. RESULTS All the studies identified excluded elderly individuals with cardiac or pulmonary disease. Patients with postradiation xerostomia and incomplete resection of the salivary glands were more likely to benefit from oral pilocarpine when there was sufficient residual glandular function than patients with radical surgery for head and neck cancer (HNC). However, patients with SS and other inflammatory disorders seemed to benefit from oral pilocarpine, when compared with patients with postradiation xerostomia. The optimal dose of oral pilocarpine, which was less likely to cause side effects, was 5 mg four times daily. A recent multi-center study in SS patients suggests that oral pilocarpine is effective and safe for long-term administration. Although some studies did not show evidence for increased salivary gland secretion rate as measured by sialometry, symptoms improved, perhaps because of increased secretion from the minor salivary glands or better conditioning of the oral mucosa. CONCLUSIONS Oral pilocarpine is likely to benefit patients with SS by reducing the symptoms of xerostomia, even if the salivary gland secretion rate does not increase. Further controlled studies are needed in patients with SS and should include elderly patients with cardiovascular disease treated with moderate doses of oral pilocarpine.

Low incidence of pulmonary complications following nonmyeloablative stem cell transplantation

Bone marrow transplantation is associated with pulmonary opportunistic infections and immune-mediated pulmonary processes such as idiopathic pneumonia syndrome and bronchiolitis obliterans. The aim of the present study was to test the hypothesis that nonmyeloablative stem cell transplantation (NST) has less adverse effects on the lungs. A review was undertaken of the pulmonary complications occurring in 53 patients with various haematological malignancies, some of whom were considered high-risk patients with chemoresistant disease, who underwent fludarabine-based irradiation-free conditioning for NST performed between March 1996 and October 1998. All data related to transplant procedure, disease outcome, graft-versus-host disease (GVHD), chest imaging, microbial cultures and lung biopsies, were retrieved from information collected prospectively at the time of transplantation. The median follow-up period after transplantation was 45 months, with 35 patients surviving >100 days. Approximately half of the patients displayed some form of GVHD, with 11% developing severe chronic GVHD. In 17 (32%) patients, the lungs were somehow adversely affected. Only two (3.8%) patients developed a clinical picture consistent with idiopathic pneumonia syndrome and none developed diffuse alveolar haemorrhage or bronchiolitis obliterans. Dose-reduced conditioning is associated with a low rate of pulmonary toxicity and side-effects. These findings may extend understanding of significant immune-mediated complications occurring after bone marrow transplantation.

Natural history of five children with surfactant protein C mutations and interstitial lung disease

Interstitial lung diseases in infants and children are uncommon and may be caused by specific inborn errors of surfactant metabolism. Five children with open lung biopsy diagnosed interstitial lung disease were followed (mean of 27.2 years) and evaluated for surfactant protein gene mutations. Four of the children were originally diagnosed as desquamative interstitial pneumonitis and one as chronic interstitial pneumonitis. All had good response to chloroquine or hydroxychloroquine treatment for periods of 7–38 months. Lung function tests, incremental exercise tests, and rentgenological studies were performed in the children. Surfactant protein gene mutations were searched in all the patients and in part of their families.

Positron emission tomography in interstitial lung disease.

Background and objectives:  A high rate of glycolysis may reflect the inflammatory activity of interstitial lung disease (ILD). This prospective study investigated whether PET can distinguish IPF, a primarily fibrotic process, from other entities of ILD that have a marked inflammatory component.

Hypothyroidism-induced myocardial damage and heart failure: an overlooked entity

BACKGROUND Hypothyroid state may induce cardiac muscle impairment such as diastolic dysfunction and abnormal relaxation time. Advanced heart failure in hypothyroid patients has been described only in severe symptomatic cases, mostly during myxedematous coma. METHODS AND RESULTS We describe an unusual case of asymptomatic patient with hypothyroidism who presented with severely reduced cardiac function with elevated cardiac enzymes reflecting significant myocardial injury. Comprehensive evaluation for heart failure was suggestive only for long-standing untreated hypothyroidism. Endomyocadial biopsy demonstrated unique histological findings of mucopolysaccharide accumulation attributed to hypothyroid state. CONCLUSIONS Asymptomatic hypothyroidism may cause severe reduction in cardiac function accompanied with elevated cardiac enzymes. To our knowledge, this is the first description of human myocardial biopsy revealing mucopolysaccharide accumulation attributed to hypothyroid state.

Pleural Effusion with Splenic Rupture as Manifestations of Recurrence of Sarcoidosis following Prolonged Remission

A 55-year-old man presented with a 3-week history of dry cough and left pleuritic chest pain with a new exudative pleural effusion. Sixteen years earlier, he was diagnosed with sarcoidosis presenting with hilar lymphadenopathy, erythema nodosum, mildly disturbed liver function tests and noncaseating granulomata on liver biopsy, with no evidence of pulmonary parenchymal disease. He was treated with prednisone and in recent years maintained at a low daily dose, until it was eventually discontinued two years prior to his present illness. There was no evidence of infection or malignancy, and the fluid resolved following treatment with naproxen. Three weeks later the patient presented with sudden onset of dyspnea and left chest pain. After starting intravenous heparin for suspected pulmonary emboli, the patient developed hemodynamic instability which was accompanied by abdominal tenderness and decreasing hematocrit. Splenic rupture was diagnosed, and the patient underwent splenectomy. Pathology specimens revealed a hemorrhagic infarct with subcapsular hematoma, and numerous noncaseating granulomata within the splenic tissue. This patient had recurrent sarcoidosis with two rare manifestations of the disease, 2 years after withdrawing low dose prednisone, given for a prolonged time. The possibility of reemergence of the disease in organs other than the organs involved in the initial presentation should always be considered in sarcoidosis.

Failure of chimerism formation and tolerance induction from Fas ligand mutant bone marrow donors after nonmyeloablative conditioning

Formation of donor-recipient mixed chimerism after nonmyeloablative conditioning allows co-existence of donor and recipient hematopoietic stem cells, with solid organ allograft tolerance and less likeliness of graft versus host development. Using a post-transplant bronchiolitis obliterans murine model, we aimed to test the hypothesis that allograft preservation after mixed chimerism formation is dependent on the presence of a functional Fas ligand (FasL) on donor hematopoietic cells. To form mixed chimerism, two aliquots of 30 × 10(6) whole bone marrow cells (BMC) from either wild-type C57BL/6 in one group, or transgenic gld mice with mutant FasL (d = 0 and 2+) in the other were used, with both groups receiving intravenous busulfan (10mg/kg) on d-1 and intraperitoneal cyclophosphamide (200mg/kg) on d+1. Tracheal allografts obtained from C57BL/6 mice were implanted into recipient BALB/c mice subcutaneously on d = 0. Tracheal allografts were harvested at d+28 post-transplant and were evaluated by histopathology. Mixed chimerism formation was detected in wild type C57BL/6 whole BMC recipients, which was accompanied by tracheal allograft acceptance with near normal structure at d+28 post implantation. However, in recipients of FasL mutant whole BMC, neither mixed chimerism formation nor tracheal allograft acceptance was obtained. We thus conclude that bone marrow cells lacking functional FasL molecules could not be engrafted in allogeneic recipients to form stable mixed chimerism after nonmyeloablative conditioning, thus not allowing tracheal allograft acceptance.

Increased energy expenditure during posture maintenance and exercise in early Parkinson disease

Evidence for the effects of Parkinson disease on energy expenditure is incomplete and contradictory. A number of studies showed increased resting energy expenditure among patients with Parkinson disease whereas others did not. It was hypothesized that energy expenditure increases during exercise, based on findings in patients with a variable regime of anti‐parkinsonian therapies and at different stages of the disease. However, energy expenditure during posture maintenance has been neglected. To better understand these issues, we studied energy expenditure in a homogenous population of Parkinson patients in an early stage of the disease and different states of activity.

Interpreting the Incremental Cardiopulmonary Exercise Test

The incremental cardiopulmonary exercise test (CPET) is an increasingly used diagnostic method that serves to evaluate patients with chief complaint of dyspnea during exercise. Performing maximal symptom-limited CPET can show if the tested subject has a reduced exercise capacity and give clues to the mechanism of such exercise capacity reduction, cardiac, pulmonary, or pulmonary vascular source. In this review, it is suggested that the evaluation of the complex results of CPET should be performed by first determining if myocardial/circulatory insufficiency is present and second if there is gas exchange abnormality. By looking with scrutiny at the oxygen consumption (VO2) versus work rate plot, one can see if oxygen delivery is adequate or if it is hampered by abnormally reduced blood flow through skeletal muscle. Elevated ventilatory equivalent of carbon dioxide at the ventilatory threshold and or arterial oxygen desaturation during effort, strongly suggest gas exchange abnormalities. The absence of circulatory insufficiency and gas exchange abnormalities, almost always suggest normal response to effort or deconditioning whenever peak VO2 is below the maximal predicted value.