Methomyl induced effect on fortilin and S100A1 in serum and cardiac tissue: Potential biomarkers of toxicity.

Methomyl toxicity has been reported as a cause of several accidental and suicidal fatalities. The study is evaluating the effect of lethal methomyl toxicity on fortilin and S100A1 in serum and cardiac tissues. Adult 96 female Sprague-Dawley rats were divided equally into a control (euthanized by cervical dislocation) and a study group (overdosed with methomyl). The levels of fortilin and S100A1 in serum were measured antemortem (to establish the basal levels in serum) and postmortem (to evaluate changes after methomyl exposure) using enzyme-linked immunoassay. S100A1 was immunostained in sections from cardiac tissues. Both proteins in the control were not significantly different (p > 0.05) compared with the antemortem levels. On the contrast, both biomarkers levels in the intoxicated group were remarkably higher (p < 0.001) than the control and the antemortem levels. Ventricular tissues from the intoxicated rats presented depleted S100A1 immunostain in cardiomyocytes localized mainly in the epicardium with deeply stained adjacent cardiac fibroblasts. The cardiomyocytes were damaged with a prominent loss of striations compared to normal cardiac tissues from the control. The present outcomes explain to a certain degree the potential toxic effect of methomyl poisoning on the cardiac tissue. Both proteins could be added to the currently available battery of markers for assessing methomyl toxicity.

8-Hydroxy-2'-deoxyguanosine (8-OHdG) as a short-term predictor of regional and occupational health problems.

Exposure to a large number of environmental toxins can induce damage to DNA and may play an important role in the pathophysiological processes of atherosclerosis. To examine the effect of some specific environmental conditions that predispose to sudden coronary atherosclerotic death on the level of 8-OHdG, urine samples were collected from cases of certain occupations and polluted regions that showed a high prevalence of premature deaths. The samples were then analyzed for 8-OHdG. Analysis of 108 cases and 45 controls showed a significant high level of 8-OHdG in relation to occupations, habits, residency and work shift. The mean +/- standard deviation (M +/- SD) for the control group was 4.5 +/- 2.3 ng 8-OHdG/mg creatinine (n = 45), compared to 9.1 +/- 3.1 ng/mg in taxi drivers (n = 9), 10 +/- 5.5 ng/mg in chemical factory workers (n = 16), 12.0 +/- 8.9 ng/mg in paint workers (n = 9), 14.6 +/- 11.1 ng/mg in gasoline station workers (n = 15), 15 +/- 6.1 ng/mg in cement factory workers (n = 12), 16.4 +/- 3.2 ng/mg in city center inhabitants (n = 18) and 18.6 +/- 3.2 ng/mg in smokers (n = 15). These conditions at least in the pilot study done by the author, showed some form of precipitation of sudden atherosclerotic coronary death. This work proved that the recently used 8-OHdG DNA damage biomarker may be an important marker of environmental conditions that are expected to have a serious long-term impact on the cardiovascular system.

Tube thoracostomy during allogeneic stem cell transplantation does not carry an increased risk for infections or bleeding.

BACKGROUND: Candidates for stem cell transplantation may occasionally suffer from massive pleural effusions related to their disease and require tube thoracostomy. The additional risk of this procedure during allogeneic transplantation procedure is not known. METHODS: Four high-risk patients transplanted in our institution during a 2-yr period had chest drainage by tube thoracostomy. The characteristics of the fluid, the clinical course, and the outcome were assessed. RESULTS: A total of nine chest drains were inserted (range 1-5). No bleeding complications related to the procedure were noted. None of the patients developed any clinical signs of local infection at the tube insertion site or within the pleural fluid. All cultures taken from the drained fluid or from the insertion wound were negative. CONCLUSIONS: Tube thoracostomy in itself does not seem to pose additional risks in the transplant procedure, despite all patients in this series being considered to be at high-risk for complications.

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.

Closed pleural needle biopsy: predicting diagnostic yield by examining pleural fluid parameters.

OBJECTIVE: Pleural fluid parameters that predict a diagnostic closed pleural needle biopsy were investigated. DESIGN: A retrospective analysis. SETTING: The Institute of Pulmonology, Hadassah University Hospital. PATIENTS AND METHODS: Forty-four patients who underwent closed pleural needle biopsies were included in this study. Pleural fluid values of protein, glucose, lactate dehydrogenase (LDH), pH, and white blood cell count with differential cell counts, from patients with diagnostic and non-diagnostic pleural biopsies were compared. RESULTS: Thirteen patients (29%) had diagnostic biopsies. Malignancy was identified in 10 patients (23%), of whom 70% had adenocarcinoma. Three other patients had non-malignant specific diagnosis. LDH levels in pleural fluid from patients with diagnostic pleural biopsy were higher than in patients with non-diagnostic pleural biopsies (1436 +/- 333 U l(-1) vs. 775 +/- 109 U l(-1); P < 0.05). LDH levels less than 510 U l(-1) were highly predictive of a negative biopsy (negative predictive value of 86.6%). Follow up revealed malignancy including mesothelioma and lymphoma, in 10 of 30 (33%) patients with non-diagnostic biopsies, and one patient died of unrelated cause, while the pleural effusion either resolved, remained stable or an alternative benign process was identified in 19 patients (63%). CONCLUSIONS: Low levels of LDH (< 510 U l(-1)) were highly predictive of a negative pleural needle biopsy. Thus, LDH may serve as a useful guide in deciding whether to perform closed pleural biopsy or to proceed to thoracoscopically guided biopsy.

Invasive airway aspergillosis with new airflow obstruction mimicking post-BMT bronchiolitis obliterans.

A 52-year-old male with severe gastrointestinal graft-versus-host disease (GVHD), developed dyspnea and irreversible airflow obstruction, 11 weeks post-allogeneic bone marrow stem cell transplantation. Based on the clinical picture and presence of 'mosaic attenuation' pattern on chest high-resolution computerized tomography (HRCT), he was presumed to have bone marrow transplantation-related bronchiolitis obliterans. Post-mortem examination revealed invasive airway aspergillosis with no evidence of bronchiolitis obliterans.

The role of BAL in the diagnosis of pulmonary mucormycosis.

Five patients with pulmonary mucormycosis diagnosed during life are described. All had underlying predisposing conditions: either posttransplant or hematologic malignancies. In all cases, the diagnosis was made using fiberoptic bronchoscopy. In three patients, BAL was diagnostic. In two of these patients, the diagnosis was made by identifying the typical hyphae of mucormycosis in the BAL fluid alone. Transbronchial biopsy was diagnostic in three patients. Treatment was based on IV antifungal chemotherapy together with surgical removal of involved lung tissue whenever feasible. The clinical outcome of these patients was dismal and was determined primarily by the underlying condition.

The role of fibre-optic bronchoscopy in solid organ, transplant patients with pulmonary infections.

Organ transplantation is currently the standard therapy for patients with end-stage organ dysfunction. The immunosuppression caused by this therapy increases the rate of infection, particularly in the lungs. Early diagnosis is extremely important and fibre-optic bronchoscopy is a helpful tool in reaching diagnosis. Knowing the timing of various pathogens following transplantation, and the radiological picture as well as the prophylactic regimen, is helpful when specific pathogens are suspected. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsies are particularly helpful in diagnosis of bacterial cytomegalovirus (CMV) and pneumocytosis carinii pneumocytosis, and is considered a safe procedure. Open lung biopsy is reserved for those who have negative bronchoscopy with a reasonable prognosis.

The use of oral pilocarpine in xerostomia and Sjögren's syndrome.

OBJECTIVES: To analyze the role of oral pilocarpine in the treatment of xerostomia of Sjogren's 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.

Increased serum CA 19-9 antibodies in Sjögren's syndrome.

A 67-year-old woman with a history of thyroiditis presented with recent intermittent epigastric pain and nausea. Hyperamylasaemia, oedema of the pancreas, and high serum levels of lipase and CA 19-9 were found. Xerostomia and dry eyes developed later, accompanied by an abnormal Schirmer's test. The diagnosis of Sjögren's syndrome was confirmed by increased anti-Ro and anti-La antibodies and the histological findings of parotid gland biopsy. Two additional cases of Sjögren's syndrome with elevated serum CA 19-9 are also described. These observations of elevated serum lipase and serum CA 19-9 in Sjögren's syndrome without evidence of malignancy may reflect pancreatic involvement in this disorder.

Induction of graft versus leukemia effects by cell-mediated lymphokine-activated immunotherapy after syngeneic bone marrow transplantation in murine B cell leukemia.

The feasibility of inducing graft versus leukemia (GVL) effects with allogeneic T cells in recipients of autologous bone marrow transplantation (BMT) was studied in a murine model (BCL 1) of human B cell leukemia/ lymphoma. Allogeneic cell therapy, induced by infusion with peripheral blood lymphocytes, a mixture of allogeneic spleen and lymph node cells and allogeneic activated cell therapy, induced by in vitro recombinant-interleukin-2(rIL-2)-activated allogeneic bone marrow cells in tumor-bearing mice, prevented disease development in adoptive BALB/c recipients. Concomitant in vivo activation of allogeneic lymphocytes with rIL-2 suppressed even more effectively the development of leukemia in secondary adoptive recipients of spleen cells obtained from treated mice. In contrast, in vivo administration of rIL-2 after syngeneic BMT, with or without equal numbers of syngeneic lymphocytes, led to disease development in secondary recipients. Our data suggest that effective cell therapy can be achieved after SBMT by allogeneic but not syngeneic lymphocytes and that anti-leukemic effects induced by allogeneic lymphocytes can be further enhanced by in vitro or in vivo activation of allogeneic effector cells with rIL-2. Therefore, cell therapy by allogeneic lymphocytes following autologous BMT could become an effective method for inducing GVL-like effects on minimal residual disease provided that graft versus host disease can be prevented or adequately controlled.