Real-time detection and identification of aqueous chlorine transformation products using QTOF MS

A screening technique has been developed that allows the rapid, real-time detection and identification of major transformation products of organic contaminants during aqueous oxidation experiments. In this technique, a target contaminant is dissolved in buffered water and chlorinated by the addition of sodium hypochlorite to give a free chlorine residual of 3 mg/L. Solution from the reaction vessel is combined with methanol and pumped directly into the electrospray ionization source of a quadrupole time-of-flight mass spectrometer (QTOF MS). The real-time decay of the target contaminant and the formation/decay of transformation products are then monitored using the QTOF MS. Subsequently, accurate mass measurements with internal mass calibration (<5 ppm mass error) and product ion scans are employed to identify these transformation products. Unlike other techniques, it requires no liquid chromatography, derivatization, or quenching of residual chlorine, all of which can interfere with transformation product analysis. To validate the technique, aqueous chlorination experiments were performed on triclosan, a previously studied environmental contaminant. Earlier research showing that triclosan underwent chlorine addition to form mono- and dichlorinated transformation products was successfully reproduced, demonstrating the feasibility of the technique. In addition, the technique revealed the formation of a stable oxygen radical-containing transformation product resulting from the oxidation of either mono- or dichlorinated triclosan. This triclosan transformation product was determined to have an empirical formula of C12H4O3Cl4 with 3.9 ppm mass error. Furthermore, atorvastatin, a commonly prescribed medication and environmental contaminant, was subjected to aqueous chlorination and studied with the technique. Atorvastatin underwent hydroxylation to form two transformation products with the empirical formulas C33H34FN2O6 (1.8 ppm mass error) and C26H29O5NF (2.9 ppm mass error).     

Primary-care-based randomised placebo-controlled trial of antibiotic treatment in acute maxillary sinusitis

BACKGROUND: The value of antibiotics in acute rhinosinusitis is uncertain. Although maxillary sinusitis is commonly diagnosed and treated in general practice, no effectiveness studies have been done on unselected primary-care patients. We used a randomised, placebo-controlled design to test the hypothesis that there would be an improvement associated with amoxycillin treatment for acute maxillary sinusitis patients presenting to general practice. METHODS: Adult patients with suspected acute maxillary sinusitis were referred by general practitioners for radiographs of the maxillary sinus. Those with radiographic abnormalities (n = 214) were randomly assigned treatment with amoxycillin (750 mg three times daily for 7 days; n = 108) or placebo (n = 106). Clinical course was assessed after 1 week and 2 weeks, and reported relapses and complications were recorded during the following year. FINDINGS: After 2 weeks, symptoms had improved substantially or disappeared in 83% of patients in the study group and 77% of patients taking placebo. Amoxycillin did not influence the clinical course of maxillary sinusitis nor the frequency of relapses during the 1-year follow-up. Radiographs had no prognostic value, nor were they an effect modifier. Side-effects were recorded in 28% of patients given amoxycillin and in 9% of those taking placebo (p < 0.01). The occurrence of relapses was similar in both groups (21 vs 17%) during the follow-up year. INTERPRETATION: Antibiotic treatment did not improve the clinical course of acute maxillary sinusitis presenting to general practice. For these patients, an initial radiographic examination is not necessary and initial management can be limited to symptomatic treatment. Whether antibiotics are necessary in more severe cases warrants further study.     

Influence of an oligodendroglial component on the survival of patients with anaplastic astrocytomas: a report of Radiation Therapy Oncology Group 83-02

PURPOSE: Seven percent of patients with high grade gliomas enrolled in RTOG 83-02 had mixed astrocytoma/oligodenroglial elements on central pathology review. It has often been assumed that the most aggressive histologic component of a tumor determines biologic behavior; however in this trial, the survival of patients who had mixed glioblastomas/oligodenrogliomas was significantly longer than that of patients with pure glioblastomas (GBM). We therefore evaluated the effect of an oligodendroglial component on the survival of patients who had anaplastic astrocytomas (AAF) treated in the same trial. METHODS AND MATERIALS: One hundred nine patients who had AAF and 24 patients with mixed AAF/oligodendrogliomas (AAF/OL) were enrolled in a Phase I/II trial of randomized dose-escalation hyperfractioned radiotherapy plus BCNU. AAF/OL patients were older and more likely to have had more aggressive surgery than AAF patients. Other pretreatment characteristics were balanced between groups, as was assigned treatment. RESULTS: The median survival time for AAF was 3.0 years versus 7.3 years for AAF/OL (p = 0.019). In a multivariate analysis, adjusting for extent of surgical resection and age, an oligodendroglial component was an independent prognostic factor for survival. CONCLUSION: The results support the concept that AAFs with an oligodendroglial component have a better prognosis than pure AAF tumors, similar to the effect seen among patients with glioblastoma multiforme tumors. This better survival outcome should be taken into consideration in the design and stratification of future trials. Additionally, in contrast to patients with GBMs, patients who have AAF/OL have the potential for prolonged survival; therefore, late sequelae of treatment (both radiation and chemotherapy) must be weighed more heavily in the benefits to risks analysis.     

Isolated left superior vena cava to the left atrium with situs solitus and dextrocardia: extracardiac repair facilitated by juxtaposition of the atrial appendages

We describe an extremely unusual case, with isolated left superior vena cava to the left atrium, normal intracardiac anatomy, and left juxtaposition of the atrial appendages. Surgical repair was performed without cardiopulmonary bypass by anastomosing the left superior cava to the superior aspect of the right atrial appendage, and was facilitated by the ectopic location of the appendage.     

Occurrence of verocytotoxin-producing Escherichia coli O157 on Dutch dairy farms

During the period from September 1996 through November 1996, 10 Dutch dairy farms were visited to collect fecal samples from all cattle present. The samples were examined for the presence of verocytotoxin (VT)-producing Escherichia coli (VTEC) of serogroup O157 (O157 VTEC) by immunomagnetic separation following selective enrichment. Cattle on 7 of the 10 dairy farms tested positive for O157 VTEC, with the proportion of cattle infected varying from 0.8 to 22.4%. On the seven farms positive for O157 VTEC, the excretion rate was highest in calves ages 4 to 12 months (21.2%). In a follow-up study, two O157 VTEC-positive farms and two O157 VTEC-negative farms identified in the prevalence study were revisited five times at intervals of approximately 3 months. Cattle on each farm tested positive at least once. The proportion of cattle infected varied from 0 to 61.0%. Excretion rates peaked in summer and were lowest in winter. Again, the highest prevalence was observed in calves ages 4 to 12 months (11.8%). O157 VTEC strains were also isolated from fecal samples from horses, ponies, and sheep and from milk filters and stable flies. O157 VTEC isolates were characterized by VT production and type, the presence of the E. coli attaching-and-effacing gene, phage type, and pulsed-field gel electrophoretic genotype. No overlapping strain types were identified among isolates from different farms except one. The predominance of a single type at each sampling suggests that horizontal transmission is an important factor in dissemination of O157 VTEC within a farm. The presence of more than one strain type, both simultaneously and over time, suggests that there was more than one source of O157 VTEC on the farms. Furthermore, this study demonstrated that the O157 VTEC status of a farm cannot be ascertained from a single visit testing a small number of cattle.     

1,N2-propanodeoxyguanosine adducts: potential new biomarkers of smoking-induced DNA damage in human oral tissue

Diarrhea is a non-specific symptom which may be associated with Addison's disease and several causes had been demonstrated in the aetiology. We describe a patient with Addison's disease who was suffering from chronic diarrhea for three months. She was diagnosed as having collagenous colitis and successfully treated with Sulphasalazine, 2 g/day. Collagenous colitis is an uncommon cause of chronic diarrhea and the association of collagenous colitis with Addison's disease has not previously been described. We think that collagenous colitis may play a role in the aetiology of diarrhea in patients with Addison's disease and therefore we suggest a full colonoscopic examination in other patients with Addison's disease and diarrhea to determine the incidence of collagenous colitis in the aetiology of diarrhea.     

Rapid, corticosterone-induced disruption of medullary sensorimotor integration related to suppression of amplectic clasping in behaving roughskin newts (Taricha granulosa)

Endogenously secreted or injected corticosterone (CORT) rapidly suppresses courtship clasping in male roughskin newts (Taricha granulosa) by an action on a specific neuronal membrane receptor. Previous studies, using immobilized newts, showed that CORT administration rapidly depresses excitability of reticulospinal neurons and attenuates medullary neuronal responsiveness to clasp-triggering sensory stimuli. The present study used freely moving newts to examine clasping responses and concurrently record sensorimotor properties of 67 antidromically identified reticulospinal and other medullary reticular neurons before and after CORT injection. Before CORT, reticulospinal neurons fired in close association with onset and offset of clasps elicited by cloacal pressure. Reticulospinal neurons also showed firing correlates of nonclasping motor events, especially locomotion. Neuronal activity was typically reduced during clasping and elevated during locomotion. Medullary neurons that were not antidromically invaded (unidentified neurons) usually showed sensorimotor properties that resembled those of reticulospinal neurons. Intraperitoneal CORT (but not vehicle) reduced the probability and quality of hindlimb clasping in response to cloacal pressure, especially within 5-25 min of injection. Simultaneously, responses of reticulospinal and unidentified neurons to cloacal pressure and occurrence of clasping-related activity were attenuated or eliminated. CORT effects were relatively selective, altering clasping-related neuronal activity more strongly than activity associated with nonclasping motor events. The properties of CORT effects indicate that the hormone impairs clasping by depressing processing of clasp-triggering afferent activity and by disrupting the medullary control of clasping normally mediated by reticulospinal neurons. The rapid onset of these CORT effects implicates a neuronal membrane receptor rather than genomic action of the steroid.     

High doses of a helper-dependent adenoviral vector yield supraphysiological levels of alpha1-antitrypsin with negligible toxicity

Optimal gene therapy for many disorders will require efficient transfer to cells in vivo, high-level and long-term expression, and tissue-specific regulation, all in the absence of significant toxicity or inflammatory responses. While recombinant adenoviral vectors are efficient for gene transfer to hepatocytes, their usefulness is limited by short duration of expression related, at least in part, to immune responses to viral proteins and by a low capacity for foreign DNA. A number of systems have been developed for producing adenoviral vectors devoid of all viral coding sequences. Using AdSTK109, a vector lacking all viral coding sequences and carrying the complete human alpha1-antitrypsin (hAAT) genomic DNA locus, we have demonstrated sustained expression for longer than 10 months in mice. Utilizing high doses of this vector for hepatic gene transfer in mice, we find that supraphysiological levels of hAAT can be achieved without hepatotoxicity.     

Morphological transformation of C3H/M2 mouse fibroblasts by extracts of human mammary lipid

The aim of this study was to determine whether suckling-induced prolactin (PRL) levels were modified when milk ejection was impaired. Milk ejection impairment was achieved in two experimental models: a) depriving the dam of sleep during suckling and b) increasing the nonsuckling intervals in lactating dams. Sleep deprivation blocked milk ejection and enhanced suckling-induced PRL levels in dams that had been previously separated from their pups. When milk ejection is blocked in litter-deprived dams, mammary glands are not evacuated and they remain engorged. Suckling stimuli were not the cause of the difference in suckling-induced serum PRL levels in control and sleep-deprived dams. The engorgement of the mammary glands may play a role, as a maximum suckling-induced PRL increase was not observed in nonseparated SD dams with nonengorged mammary glands. Moreover, suckling-induced PRL levels were decreased when engorged mammary glands of SD dams were evacuated through an oxytocin injection. A parallel increase between suckling-induced PRL levels and mammary gland weight was observed in the experiments in which milk ejection was impaired through an increase in the intervals of nonsuckling, providing additional support for a relationship between mammary gland engorgement and the regulation of suckling-induced PRL levels.