Nephrotoxicity issues of organophosphates.

Organophosphates are a large class of chemicals, initially invented in 1850 and since then they have been applied in numerous aspects of science to serve our purposes. Their mechanism of action in living organisms involves the irreversible inhibition of acetylcholinesterase, therefore they interfere with neuromuscular signal transmission. Due to the systematic and exaggerated use of these chemicals, there is massive exposure to them, hence there is great concern regarding the ramifications to all mammalian organisms. It has been widely accepted that over-exposure to organophosphates, has a deleterious impact on the renal tissue and subsequently on the renal function. Despite the significance of this global issue, limited knowledge exists, regarding the effect of these substances on our health. Therefore, new and extensive research is required to expand our knowledge and ensure proper guidance regarding the use of organophosphates as well the protection against their detrimental consequences. The aim of this review is to negotiate the effect of organophosphate exposure on renal tissue and kidney function.

Erratum - Osteophytes may be a rare cause of recurrent pleural effusions

This corrects the article published on Monaldi Archives for Chest Disease 2013;79(2):87-89.

Erratum - Osteophytes may be a rare cause of recurrent pleural effusions.

This corrects the article published on Monaldi Archives for Chest Disease 2013;79(2):87-89.

Osteophytes may be a rare cause of recurrent pleural effusions.

We report a rare case of a 59 year-old female, who was admitted to the hospital because of a recurrent right-sided pleural effusion. The initial work-up was non-diagnostic. The diagnosis was finally confirmed following medical thoracoscopy, where an osteophyte of a rib was found to protrude sharply into the thoracic cavity. Chronic inflammatory changes of the pleura suggested mechanical irritation due to long lasting friction between this bony structure and the underlying lung. This is the first report where an osteophyte seems to be implicated in pleural pathology. A brief review of the available data from the literature is presented to further support our results.

Pulmonary fibrosis presenting as an early manifestation of microscopic polyangiitis.

Microscopic polyangiitis (MPA) is a systemic small vessel vasculitis that is included in the pulmonary-renal syndromes. Although glomerulonephritis represents the major clinical feature of MPA indicative of renal involvement, diffuse alveolar haemorrhage is the classic manifestation of pulmonary involvement. However, pulmonary fibrosis is a less frequently reported pulmonary manifestation. Herein we describe a patient who was diagnosed with MPA presenting with radiographic evidence of pulmonary interstitial fibrosis as an early clinical manifestation accompanied by constitutional symptoms such as fever and weight loss. We also include a short literature review focusing on the association between pulmonary fibrosis and MPA.

Tuberculosis and granuloma formation in patients receiving anti-TNF therapy.

In patients receiving anti-tumor necrosis factor (TNF) therapy, a probable exacerbation of latent tuberculosis (TB) is a major adverse event. The impairment of granuloma differentiation is considered a characteristic feature of TB in these patients. In this report we present three patients with rheumatic disease who developed TB under infliximab treatment. All of them had typical granulomas on the biopsy specimens, indicating that the expected impairment of granuloma formation is not always the case. The notion of granuloma-free TB in patients receiving anti-TNF therapy could shift a clinician's path away from performing a biopsy, thus delaying the establishment of a correct diagnosis.

Exhaled markers of oxidative stress in idiopathic pulmonary fibrosis.

BACKGROUND: Expired breath condensate (EBC) has never been used to explore the level of oxidative stress in idiopathic pulmonary fibrosis (IPF). Therefore, the aim of this study was to measure the levels of H2O2 and 8-isoprostane, as biomarkers of oxidative stress, in the EBC of patients with IPF. MATERIALS AND METHODS: We investigated 16 patients with IPF and 15 healthy subjects as the control group. The levels of H2O2 and 8-isoprostane were measured in the EBC of all subjects and were compared between the IPF and control groups. In patients with IPF, H2O2 and 8-isoprostane were further correlated with pulmonary function tests (PFTs), the resting pO2 and the differential cell count from the bronchoalveolar lavage fluid (BALF). RESULTS: The mean (95%CI) concentration of H2O2 was increased in the patients with IPF compared with the normal subjects (0.36, 0.24-0.47 microM vs. 0.16, 0.10-0.23 microM, P=0.003). The mean (95%CI) concentration of 8-isoprostane was also increased in the patients with IPF compared with the controls (74, 38-110 pg mL-1 vs. 33, 28-39 pg mL-1, P=0.02). In the patients with IPF, the diffusing capacity of the lung for carbon monoxide was negatively correlated with the levels of H2O2 in EBC (P=0.03, r=-0.58). No other correlation was found between the oxidative stress markers in the EBC and PFT values, pO2 or BALF cell count. CONCLUSIONS: Our data suggest that H2O2 and 8-isoprostane are increased in the EBC of patients with IPF. H2O2 may be correlated with the severity of the disease in IPF.

The neutrophilic and fibrinolytic response to talc can predict the outcome of pleurodesis.

It was hypothesised that monitoring neutrophil and D-dimer (DD) levels into the pleural fluid, after talc instillation, could predict the outcome of pleurodesis. The current authors investigated a total of 168 patients with malignant pleural effusion, who were treated with talc poudrage. According to the outcome the patients were categorised into one of two groups, either successful or failed pleurodesis. In all cases, pleural fluid neutrophils and DDs were determined on serial measurements at 0, 3, 24 and 48 h after the procedure. The time course of these parameters was assessed in both groups and the time point at which they could better predict the outcome was further explored. Neutrophils rose rapidly after talc poudrage in both groups, reaching a plateau at 24 h, although in successful pleurodesis this response was significantly higher. DD dropped markedly at 24 h in the group with the successful outcome, but it did not show significant changes in the other group. A cut-off value of 61% for neutrophils and 61 mg.L-1 for the DD at 24 h yielded the best prognosis for successful pleurodesis. The current authors conclude that serial measurements of neutrophil and d-dimer values into the pleural fluid after talc poudrage could be used as predictors of the outcome of pleurodesis.

Simultaneous pulmonary and intrathoracic lymph nodal granulomatosis of unknown significance (GLUS).

A case of a 30-year-old male with a fever, dry cough and associated abnormal findings in imaging modalities (bilateral hilar lymphadenopathy and nodular parenchymal opacities) is described. After a further and scrutinized work-up, the diagnosis of GLUS syndrome was made. Clinical, etiological, pathological and therapeutical aspects of the disease are discussed, demonstrating the paramount importance of the use of the immunohistochemical methods in the diagnosis of this disorder.

The prevalence of congenital bronchial atresia in males.

BACKGROUND: Congenital bronchial atresia is a rare anomaly, which usually occurs in adulthood as an incidental finding on routine chest radiograph. METHODS: The purpose of the study was to retrospectively evaluate the cases that were diagnosed in our hospital, from January 1995 to March 2003, to estimate the prevalence of this disorder and to determine the diagnostic studies of choice, according to the existing literature. Since the main portion of the male population of our country is referred to our hospital for screening soon after their enrollment in the army, epidemiological data can be easily estimated for many congenital anomalies occuring in adulthood, such as bronchial atresia. RESULTS: We found seven patients with Congenital Bronchial Atresia and the prevalence of this disorder was estimated at 1.2 cases per 100,000 in males. The chosen diagnostic procedure is computed tomography of the chest with high-resolution scans. Bronchoscopy would only exclude serious alternative diagnosis and prevent unnecessary surgical interventions. CONCLUSIONS: Congenital bronchial atresia is a rare anomaly, with a mild clinical course. The diagnosis is made radiologically, the HRCT of the chest being the procedure of choice. Bronchoscopy should be performed to exclude any endobronchial lesion due to a different disease entity and to prevent unnecessary surgical intervention in an otherwise asymptomatic individual.

Prostaglandin E2 in the expired breath condensate of patients with asthma.

Inhaled prostaglandin (PG)E2 has been found to cause bronchodilation in asthmatics, although it does not have bronchodilative effects in normal subjects. The aim of this study was to investigate the levels of PGE2 in the expired breath condensate of patients with asthma, the possible contribution of smoking habit to its levels and the possible relationship between PGE2 and the degree of bronchial hyperresponsiveness, as assessed by the provocation dose of histamine causing a 20% fall in forced expiratory volume in one second (FEV1) (PD20). A total of 30 mild asthmatics (15 smokers, all steroid-naive, FEV1 88+/-6 (%+/-SD)) and 20 healthy control subjects (10 smokers) were studied. Histamine challenge testing was performed in all subjects and the PD20 was determined. The results showed that asthmatic smokers had significantly higher values of PGE2 compared to asthmatic nonsmokers and control subjects (40+/-21 versus 14.5+/-4.5 versus 11.7+/-3 pg x mL(-1), respectively). Further analysis showed that PGE2 levels were significantly higher in asthmatic smokers compared to smoker and nonsmoker controls (40+/-21 versus 11.6+/-2 versus 11.7+/-4 pg x mL(-1), respectively). No significant difference was observed between asthmatic nonsmokers and both control smokers and control nonsmokers. No significant correlation was found between PGE2 levels and PD20 in all groups of asthmatics, irrespective of smoking habit. In conclusion, the elevation of prostaglandin E2 in the expired breath condensate of patients with asthma is mainly attributed to smoking habit and prostaglandin E2 levels do not predict the degree of bronchial hyperresponsiveness.

Magnesium levels in plasma and erythrocytes before and after histamine challenge.

Previous studies have assessed the protective effect of nebulized magnesium sulphate on bronchial hyperreactivity. This study investigated the effect of histamine challenge on intracellular (erythrocytes) and extracellular (plasma) levels of magnesium and the possible relationship between degree of bronchial hyperreactivity and levels of Mg in plasma and erythrocytes. The authors studied 42 mildly asthmatic patients (10 on inhaled steroids) and 20 healthy subjects. Histamine challenge was performed by the dosimeter method and provocative dose causing a 20% fall in forced expiratory volume in one second (PD20) (FEV1) was calculated. Mg levels were measured with a calmagite colourimetric assay, both at baseline and when FEV1 had fallen by 20%. The results showed that Mg levels in plasma did not significantly change after histamine challenge (from 2.06+/-0.02 mg x dL(-1) to 2.08+/-0.02 mg x dL(-1) respectively, p=0.14). Conversely there was a statistically significant decrease in Mg levels in erythrocytes between these two time points (from 1.84+/-0.02 fmmol x cell to 1.78+/-0.02 fmmol x cell p<0.0001). Similar results were observed when the subgroups were studied separately. There was no significant correlation between PD20, the difference in both magnesium concentrations (baseline-PD20 time) or the initial values of Mg levels in erythrocytes and plasma. To conclude, histamine challenge reduces magnesium levels in erythrocytes while plasma levels remain unchanged. This histamine-induced decrease in magnesium levels occurs regardless of the diagnosis of asthma, and it is not correlated with the degree of bronchial hyperreactivity.

Microsatellite DNA instability and loss of heterozygosity in pulmonary sarcoidosis.

In the present study we investigated the incidence of microsatellite instability (MI) and loss of heterozygosity (LOH) in sarcoidosis, a multisystem disease of unknown origin. We examined sputum cytological specimens from 30 patients with sarcoidosis and 30 healthy, matched subjects, using 10 highly polymorphic microsatellite markers located at several chromosomal arms. The electrophoretic pattern of each specimen was compared with the corresponding pattern of peripheral blood and any difference in the mobility of the microsatellite alleles was interpreted as MI-positive. LOH was scored as decrease in intensity of one allele relative to the other as determined from comparison of sputum and normal (blood) DNA. We found that 14 (47%) sarcoidosis patients showed genetic alterations, either MI or LOH. Six (20%) patients exhibited MI and nine (30%) exhibited LOH in at least one microsatellite marker. One of the patients exhibited MI in two microsatellite markers and three (10%) showed LOH in more than one marker. One patient showed complete deletion of the chromosomal arm 17q11.2-q21. None of the healthy subjects exhibited any genetic alteration in the studied markers. No correlation was found between the genetic alterations detected and age, disease duration, blood gases, or spirometric parameters of the patients. Our findings suggest that MI is a detectable phenomenon in sarcoidosis and seems not to be related with the severity of the disease. The detection of LOH indicates the presence of putative tumor suppressor genes at loci examined, which may play an important role in the etiopathogenesis of sarcoidosis.

Gastroesophageal reflux presented with haemoptysis and carinal erythematous lesion resembling in situ carcinoma.

Gastroesophageal reflux (GER) is often associated with respiratory disorders. We report an unusual case of GER presented with haemoptysis. On fibreoptic bronchoscopy (FFB) a focal erythematous lesion of the mucosa of the main carina was found. Repeated FFB and biopsy excluded in situ neoplasm. Pharmacological treatment of GER with sisapride and ranitidine resulted in complete remission of the bronchial lesions. To the best of our knowledge haemoptysis with bronchoscopic lesions due to the gastroesophageal reflux has not been described previously.