Pesticides Exposure by Air in Vineyard Rural Area and Respiratory Health in Children: A pilot study.

RATIONALE: Asthma, frequently associated with rhinitis, is the most common chronic disease in children, and a significant role is played by a range of environmental exposures. Among them, air pollution is of foremost concern. However, little is known about the impact of airborne pesticide exposure on children's respiratory health in rural areas. The objective of this study was to analyze the association between airborne pesticide exposure and asthma and rhinitis in children. METHODS: In a French vineyard rural area, children (3-10 years old) from 4 selected schools were invited to participate in this study over two periods: winter, with no or low air pesticide levels, and summer when fields are frequently treated with pesticides. Two health outcomes were considered: asthma and rhinitis symptoms (ISAAC questionnaire), and peak expiratory flow (PEF). A quantitative score of symptoms was built. Exposure to pesticides was evaluated 1) by measuring 56 pesticides in the ambient outdoor air around schools in the two periods and building a cumulative exposure index, and 2) by measuring ethylenethiourea (ETU) concentrations in urine in a subsample of children (n = 96), ETU being a urine biomarker of exposure to dithiocarbamates fungicides. Next, the association between pesticide exposure and respiratory health was studied using a logistic regression model, adjusted for confounders and respiratory status at baseline. RESULTS: 281 children participated in the study (47% girls, mean age: 7.5 yrs). 25% of the children were living on a farm. 22% had experienced wheezing at least once. 15.8% had asthma diagnosed by a doctor, 12% had current asthma and 35% had allergic rhinitis. The main pesticides detected in the ambient outdoor air around schools were fungicides (89,3%; mainly folpet and dithiocarbamates) and insecticides (10.6%). No association was found between the symptom score and pesticides in the outdoor air around schools during summer, when pesticides were applied to vineyards. However, an association was found between ETU urinary concentration (>0.974 µg/g creatinine) and asthma and rhinitis symptoms (OR=3.56; IC 95% 1.04-12.12). This result could be explained by extracurricular exposure, which was not considered in our air measurements in the schools. No association was found between peak expiratory flow and exposure to pesticides in the air. CONCLUSIONS: Children living in vineyard rural areas are at a higher risk of airborne dithiocarbamates exposure during the summer period. Despite the limited size of our sample, our results suggest possible links between some pesticide measurements and respiratory and allergic symptoms such as rhinitis.

Efficacy of intralesional sodium thiosulfate injections for disabling tumoral calcinosis: Two cases.

INTRODUCTION: Tumoral calcinosis (TC) is a difficult-to-treat complication that can occur during several diseases such as dermatomyositis or genetic hyperphosphatemia. It is a painful and disabling condition that can lead to local complications including joint mobility reduction, cutaneous ulceration and superinfection. For the largest lesions, the treatment relies essentially on surgery. Intravenous sodium thiosulfate (STS) is efficient to treat calciphylaxis in patients undergoing hemodialysis. Local injections of STS seem efficient in superficial calcifications. OBJECTIVE: To report the efficacy and safety of intra-lesional injections of STS in tumoral calcinosis. RESULTS: We report two cases of successful intra-lesional injections of STS. A 44-year-old woman, with a history of dermatomyositis, presenting large subcutaneous calcifications in the right elbow, and a 42-year-old man, with a history of familial tumoral calcinosis, presenting large intramuscular calcifications in the right buttock, received weekly intra-lesional of 1-3g STS injections for 12 and 21 months, respectively. In both cases, the treatment relieved pain and greatly reduced the tumoral calcinosis with a very significant functional improvement without specific adverse effects. In case 1, TC size decreased from 28.7*56.0mm at baseline to 21.5*30.6mm at M12 treatment (59% reduction). In case 2, TC reduced from 167.5*204.3mm at baseline to 86.2*85.2mm at M21 treatment (79% reduction). CONCLUSION: Local injection of STS could be a promising therapeutic strategy for large and deep TC lesions and could therefore be an alternative to surgery.

Relationship between microsatellite instability, response and survival in palliative patients with colorectal cancer undergoing first-line chemotherapy.

BACKGROUND AND AIMS: The aim of this work was to investigate the relationship between microsatellite instability (MSI), treatment response and survival in palliative patients with colorectal cancer (CRC) undergoing first-line treatment with weekly 24-hour infusion (24-h inf.) of high-dose 5-fluorouracil (5-FU) and folinic acid (FA). PATIENTS AND METHODS: Tumour material from the colorectal primary carcinomas was analysed for 43 patients. MSI analysis was carried out and immunohistochemistry was performed with hMLH1 and hMSH2. RESULTS: Tumours of 7 patients (16%) were highly instable (MSI-H). These patients had a better response rate (72% vs. 41%; p = 0.072) and a significantly better median survival (33 months, [95% CI 20-46] vs. 19 months, [95% CI 10-28]; p = 0.021) than microsatellite stable (MSS) patients (n = 36). Furthermore, MSI status was shown to be an independent predictive marker for survival (p = 0.037). CONCLUSION: These data provide further support for the hypothesis that MSI-H CRC might have a better response and survival than (MSS) CRC in palliative first-line treatment.

Prevention of biliary stent occlusion by ursodeoxycholic acid plus norfloxacin: a multicenter randomized trial.

We report a prospective randomized multicenter trial that tested the efficacy of combining ursodeoxycholic acid and norfloxacin in the prevention of polyethylene stent clogging in patients with obstructive jaundice due to an unresectable malignancy at the level of the common bile duct. After insertion of a 10-Fr straight polyethylene stent, patients were allocated to receive oral treatment with ursodeoxycholic acid and norfloxacin, or conservative treatment. The primary outcome measure was stent blockage within six months. Thirty-three patients (group I) received ursodeoxycholic acid and norfloxacin, and 29 received conservative treatment (group II). At six months, cumulative stent patency rate did not differ significantly between group I (47+/-11%, mean +/- SE, median 149 days) and group II patients (24+/-10%, mean +/- SE, median 100 days, P = 0.23, log-rank test). Four stents were clogged by ursodeoxycholic acid. Survival did not differ between the two groups. Combined therapy with ursodeoxycholic acid and norfloxacin failed to improve stent patency. Moreover, ursodeoxycholic acid can cause stent obstruction.

Polyethylene stent blockage: a porcine model.

BACKGROUND: Endoscopic insertion of biliary stents is a useful treatment for obstructive jaundice resulting from unresectable tumors of the pancreas and biliary tree. The main drawback is the recurrence of jaundice due to clogging. The aim of this study was to establish an experimental model of polyethylene stent clogging in large white pigs. METHODS: A straight polyethylene stent of 5F (group I), 7F (group II) or 10F size (group III) was inserted in the common bile duct. Animals were killed at 2 months, or earlier if physical signs suggesting stent clogging occurred. Chemicophysical analysis of stent deposition combined stereomicroscopy and identification of the contents by means of Fourrier transform infrared spectroscopy. Bacteriologic analyses included identification of aerobic and anaerobic bacteria and measurement of beta-glucuronidase, lecithinase and lipase activities. RESULTS: Physical signs suggesting stent obstruction or death occurred in 8 of 8 animals in group I, 11 of 12 in group II, and 2 of 8 in group III (p < 0.001). The proportion of mucoprotein in the stent contents tended to fall with increasing stent diameter (mean 82%, 58% and 47% for 5F, 7F and 10F, respectively), whereas wheat starch and calcium bilirubinate content increased with increasing stent diameter (9% and 4%, 18% and 10%, and 29% and 23% for 5F, 7 F, and 10F, respectively), although none of these differences were statistically significant. A variety of bacteria were cultured from the stent deposits, including anaerobic strains. Clostridium species were associated with the highest enzyme activities. CONCLUSIONS: In this model the major component of early stent deposits was mucoprotein, and numerous aerobic and anaerobic bacteria were isolated. Formation of calcium bilirubinate was a late phenomenon and poorly related to bacterial enzymatic activities.

Genetic instability of a dinucleotide repeat-rich region in three hematologic malignancies.

Microsatellite instability is a newly identified mechanism of mutation that occurs in some heritable neurological and muscular disorders, as well as in an increasing number of human cancers. To extend previous data, we examined the genetic instability of a human genomic region, termed S3/1, which we isolated from a human DNA library. The S3/1 sequence contains a stretch with exceptionally high numbers of (GA)n and (CA)n dinucleotide repeats. An interesting rearranged pattern emerged from Southern blot analysis of genomic DNA from three patients with different hematopoietic proliferative diseases out of 69 analyzed (one case of essential thrombocytosis (ET), one of chronic myelogenous leukemia (CML) and one of acute myelogenous leukemia (AML)). The CML and ET patients showed a deletion of 300 to 400 base pairs (bp), and the AML an insertion of about 600 bp, involving the S3/1 locus. Amplification of the rearranged fragments confirmed these observations, and enabled a precise analysis of the region involved. In normal individuals, no gross rearrangements involving this region could be detected. Analysis of DNA from three consecutive bone marrow biopsies of the CML patient disclosed that the genetic alteration affecting S3/1 was no longer detectable following alpha 2-interferon therapy, neither by Southern blot nor by polymerase chain reaction (PCR), thus confirming the tumor-specificity of the alteration; in the same patient, moreover, two out of five other analyzed microsatellites showed tumor-specific alleles, suggesting a more generalized genetic instability in the leukemic cells. These results demonstrate genetic instability of a region containing high numbers of short dinucleotide repeats in a small percentage (4%) of human hematopoietic proliferative disorders.

Potential nephrotoxicity of intravenous infusions of naftidrofuryl oxalate.

We report two cases of acute renal failure in patients with arteriosclerosis obliterans treated by intravenous infusion of naftidrofuryl oxalate. At renal biopsy the histological lesions were identical with those found in ARF due to hyperoxaluria of other causes, revealing tubular epithelial necrosis and massive intratubular precipitation of calcium oxalate monohydrate (C1) crystals. A second study was then conducted in four other patients with arteriosclerosis obliterans to evaluate serum and urinary levels of oxalate, and crystalluria during the intravenous administration of 800 mg of naftidrofuryl oxalate per day for 10 days. During the course of treatment, the serum and urinary oxalate levels were found to increase substantially, with the gradual onset of massive C1 crystalluria. These results indicate that naftidrofuryl oxalate was responsible for the acute renal failure in the first two patients. High intravenous doses of naftidrofuryl oxalate must be used cautiously, with close surveillance of renal function.

Productive expression state confers resistance of human immunodeficiency virus (HIV)-2-infected lymphoma cells against superinfection by HIV-1.

In the past, positive as well as negative results pertaining to HIV-1/HIV2 interference have been obtained. Therefore, in the present study attention was paid to the viral expression state of preinfected cells at the time of exposure to secondary virus. A clonal HIV-2 infected HUT-78 cell line was derived by endpoint dilution and subsequently inoculated with cell-free HIV-1. Superinfection with HIV-1 was ruled out by Western blot and PCR analysis. The chronically HIV-2 infected cells used for these studies showed a highly productive expression state, as evidenced by immunoperoxidase staining (IPS), Western blot profile and levels of reverse transcriptase (RT) activity. We discuss several mechanisms of interference in productively infected cells, which may confer resistance to superinfection with secondary virus.

Urinary lithiasis induced by sulfamethoxazole in a patient with tetraplegia. Case report.

Bladder lithiasis is a frequent complication in paraplegics and tetraplegics. We report on a patient where treatment of a urinary infection with antibacterial sulfamides was the causative factor in the formation of bladder stones.

[Identification of a metabolite of floctafenine in urinary calculi]. / Identification d'un métabolite de la floctafénine dans un calcul urinaire.

There are three 4-amino-quinolines used for their analgesic properties: glafenine, antrafenine and floctafenin. Urinary calculi due to glafenine have been described since 1980. Recently two cases of renal calculi containing antrafenic acid have been reported. We discovered a metabolite of floctafenin in a bladder calculus and describe its identification by infrared spectrophotometry and thin-layer chromatography.