Review of the Ecotoxicological Properties of the Methylenedianiline Substances.

Concerning chronic toxicity, D. magna is the most sensitive species tested against MDA aquatic exposures, with a 21 days-NOEC of 0.00525 mg/L. Exposure of daphnids takes place via the aquatic phase. Other species of the same phylum (Arthropoda) appear to be less sensitive albeit with exposures via soil or sediment, with a 28 days-NOEC of 562 mg/kg d. w. soil (F. candida) and 41.3 mg/kg d. w. sediment (Hyalella azteca), for reproductive and survival endpoints, respectively. Also for acute toxicity, D. magna is more sensitive than the other species, with an 48 h-EC50 that spreads over two orders of magnitude, ranging from 0.019 to 2.7 mg/L. Fish show a more uniform reaction to MDA, with 96 h-LC50 ranging from about 20 to 60 mg/L; chronic data for fish are not available. Acute toxicity data for algae and cyanobacteria are in the range of 1-10 mg/L; based on growth rate, the 72 h-NOECr or ErC10 of MDA to algae is 0.3-9.3 mg/L.For sediment organisms, the black worm L. variegatus shows the highest sensitivity against MDA with a NOEC between ≤3.75 mg/kg and 30 mg/kg d. w., followed by the amphipod H. azteca. The lower sensitivity of L. variegatus in the second study compared to the first study is obviously attributable to the different feeding regimes (semi-continuous feeding against pre-spiked sediment). One argument might be that semi-continuous feeding allows the organisms to avoid the contaminated food. However, a change from semi-continuous feeding to sediment pre-spiked with nettle powder (Urtica sp.) results in an earlier and much stronger increase in ammonia concentration in the system. This became apparent after both studies on the blackworm were finalized. The ammonia 96 h-EC50 for the blackworm is 0.69 mg/L at pH = 8.2, and the 96 h-EC10 at pH = 8.2 is 0.33 mg/L (Hickey and Vickers, Arch Environ Contam Toxicol 26:292-298, 1994). As a result, the lower NOEC and LOEC in the second study with L. variegatus are probably attributable to interference by ammonia.MDA binds irreversibly to soil and sediment which may explain the general, but not uniform lower sensitivity of soil and sediment organisms against aquatic organisms. However, species with intense soil or sediment contact (L. variegatus and E. fetida) show in general lower NOEC values than those organisms with less direct contact (3.75 and 11.2 mg/kg d. w., respectively). On the one hand it may be hypothesized that this intense contact to soil bound MDA is one reason for the higher sensitivity; on the other hand, metabolic capacity against MDA of the organisms tested is unknown at this point in time and might as well explain differences in species sensitivity. For plants there are only acute data available, and in respect to acute toxicity L. sativa is more sensitive to MDA than E. fetida.Limited aquatic data available so far do not indicate that the toxicity of pMDA is different to MDA. In addition, the limited set of data generated with the marine M. macrocopa (crustacean), N. fustulum (diatom) and V. fisheri (bacteria) do not indicate that sea water organisms are more sensitive to MDA than fresh water organisms.In mammals, MDA is unlikely to interact with the endocrine sexual system; interaction with the adrenergic system cannot be ruled out, and effects of MDA on the thyroid hormone system have been demonstrated. MDA inhibits the thyroid peroxidase which might contribute to the thyroid gland tumors observed in chronic studies with rats and mice. Some anti-androgenic activity in in vitro studies with yeast cell did not prevail in in vivo studies with rats and mice.

The use of an aeration system to prevent thermal stratification of a freshwater impoundment and its effect on downstream fish assemblages.

Warm-water riverine fish assemblages were investigated downstream of an impoundment before and after thermal stratification and the associated cold-water pollution was prevented using an aeration system. Temperatures below the dam significantly increased after installation of the aeration system and this correlated with an increased abundance and greater number of species downstream. Overall, aeration appeared to be beneficial for both the lake (upstream) and the downstream riverine environments.

Gamete compatibility between marine and estuarine Acanthopagrus spp. (Sparidae) and their hybrids.

On Australia's south-east coast, hybridization between estuary-restricted black bream Acanthopagrus butcheri Munro and its migratory coastal congener yellowfin bream Acanthopagrus australis (Günther) has led to estuarine populations largely composed of hybrids that are most genetically similar to A. butcheri. The fertilization success achieved when ova of estuary-caught A. butcheri were fertilized with the cryogenically preserved sperm of either ocean-caught A. australis or estuary-caught A. butcheri-like was compared. The experimental crosses, which by chance included both pure parental and hybrid bream, revealed no evidence that gametic incompatibility provides a barrier to fertilization among both pure species and their hybrids.

Evolutionary impacts of hybridization and interspecific gene flow on an obligately estuarine fish.

For free-spawning estuarine taxa, gene flow among estuaries may occur via hybridization with mobile congeners. This phenomenon has rarely been investigated, but is probably susceptible to anthropogenic disturbance. In eastern Australia, the estuarine Black Bream Acanthopagrus butcheri and marine Yellowfin Bream Acanthopagrus australis have overlapping distributions and the potential to hybridize. We used surveys of microsatellite and mtDNA variation in 565 adults from 25 estuaries spanning their distributional range to characterize the species and their putative hybrids. Hybrids were widespread (68% of estuaries) and hybrid frequencies varied greatly among estuaries (0-58%). Most (88%) were classed as advanced generation backcrosses with A. butcheri and displayed A. butcheri mtDNA haplotypes. We found most hybrids in the three estuaries within the zone of sympatry (57%). Our study highlights the underemphasized importance of estuaries as sites of hybridization and suggests that hybridization is driven both by opportunity for contact and human activity.

Abciximab for treatment of thromboembolic complications during endovascular coiling of intracranial aneurysms.

BACKGROUND AND PURPOSE: Thromboembolism is a recognized complication occurring during endovascular coil embolization of intracranial aneurysms. Recently, there has been much interest in glycoprotein IIb/IIIa inhibitors to treat such complications, but the evidence is limited. We reviewed our use of one such agent, abciximab, which we commonly administer and believe to be a safe and suitable rescue agent in this setting. MATERIALS AND METHODS: We retrospectively reviewed cases in which abciximab was administered in our institution between 2001 and 2007. Clinical outcome was assessed by the modified Rankin Scale (mRS) at 6 months. Good outcome was defined as no significant clinical sequelae compared with baseline status or clinical improvement (mRS < 2). Poor outcome was defined as no resolution of a new clinical deficit that developed postprocedure at 6 months (mRS > 2). Angiographic appearance of thromboembolic phenomena and posttreatment outcome was assessed with the Thrombolysis in Myocardial Infarction (TIMI) scale. RESULTS: Thirty-eight patients were included, with good outcome observed in 30 (79%) and poor outcome in 8 (21%) patients. Angiographic improvement based on TIMI scoring was seen in 24 (63%) patients, and no improvement was seen in 14 (37%). In 4 patients (11%), good outcome was obtained at 6 months despite no angiographic improvement on TIMI. No cases of intracranial rebleed or additional neurologic deficit following administration of abciximab were encountered. CONCLUSION: In this small retrospective series, abciximab was safe and effective when used as a rescue agent for thromboembolic complications encountered during coiling of intracerebral aneurysms.

Fourier space intermittency of the small-scale turbulent dynamo.

The small-scale turbulent dynamo in the high Prandtl number regime is described in terms of the one-point Fourier space correlators. The second-order correlator of this kind is the energy spectrum and it has been previously studied in detail. We examine the higher order k-space correlators, which contain important information about the phases of the magnetic wave packets and about the dominant structures of the magnetic turbulence which cause intermittency. In particular, the fourth-order correlators contain information about the mean-square phase difference between any two components of the magnetic field in a plane transverse to the wave vector. This can be viewed as a measure of the magnetic field's polarization. Examining this quantity, the magnetic field is shown to become plane polarized in the Kazantsev-Kraichnan model at large times, corresponding to a strong deviation from Gaussianity. We derive a closed equation for the generating function of the Fourier correlators and find the large-time asymptotic solutions of these correlators at all orders. The time scaling of these solutions implies that the magnetic field has log-normal statistics, whereas the wave number scaling indicates that the field is dominated by intermittent fluctuations at high k.

Superficial siderosis of the meninges and its otolaryngologic connection: a series of five patients.

OBJECTIVE: To study the otolaryngologic disorders in patients with superficial siderosis of the meninges. BACKGROUND: Superficial siderosis of the central nervous system is a rare disorder characterized by progressive bilateral hearing loss and ataxia caused by recurrent bleeding into the subarachnoid space. The cerebellum, eighth cranial nerve, and olfactory nerve are particularly susceptible to the deposition of hemosiderin, which is responsible for the symptoms. The diagnosis is confirmed by magnetic resonance imaging. METHODS: The clinical notes of five patients with superficial siderosis of the meninges were reviewed with the intent of reporting the otolaryngologic symptoms and signs, the clinical investigations, and treatments. RESULTS: Four of the five patients had sensorineural deafness, two had smell disturbances, and three had gait abnormalities. Magnetic resonance imaging was the most important investigation used to identify the condition. CONCLUSIONS: Superficial siderosis of the meninges is an important differential diagnosis in patients with progressive sensorineural deafness.

The ability of plain radiography to predict intracranial aneurysm occlusion instability during follow-up of endosaccular treatment with Gugliemi detachable coils.

Incomplete occlusion of an intracranial aneurysm at follow-up after treatment with Gugliemi detachable coils (GDC) increases the risk of rebleeding and serial angiographic monitoring is therefore currently indicated. We aimed to determine if a change in the plain radiographic appearances of the GDC ball could accurately predict the presence of unstable angiographic occlusion. Paired GDC radiographs (in two planes) and cerebral angiograms, performed immediately after treatment and at follow-up or at two consecutive follow-up examinations, were retrospectively compared. Radiographs were assessed for the radiographic change (loosening, compaction or reorientation) in the coil-ball and angiograms for unstable aneurysm occlusion (neck recurrence or deteriorating occlusion). We compared 49 paired films from 38 patients. Radiographic change in the coil ball had a negative predictive value of 96%, positive predictive value of 57% and accuracy of 76% for the presence of angiographic aneurysm instability. It may be possible to increase the interval between follow-up angiographic examinations after GDC treatment safely if there is no change in the radiographic appearances in two planes.

The C. elegans gon-2 gene encodes a putative TRP cation channel protein required for mitotic cell cycle progression.

The C. elegans gon-2 gene is required for the post-embryonic mitotic cell divisions of the gonadal precursor cells. A single major transcript of approximately 6.7 kb is derived from the gon-2 locus. This mRNA encodes a protein related to the TRP family of cation channels and has a high degree of similarity to several vertebrate genes, including melastatin. Mutant alleles of gon-2 affect evolutionarily conserved amino acid residues. Northern analyses suggest that gon-2 expression is not limited to gonadal tissues.

Biodegradation of bisphenol A in aquatic environments: river die-away.

The biodegradability of bisphenol A (BPA) was assessed in surface waters from seven different rivers across the United States and Europe. Rapid biodegradation of BPA was observed in all rivers following lag phases ranging from 2 to 4 d. Biodegradation half-lives for BPA were typically less than 2 d following the lag phase. Mineralization of BPA was observed in all river waters, with average carbon dioxide yields of approximately 76% of the theoretical maximum (range 59-103%) at the end of the incubation period (< or = 18 d). Short half-lives (0.5 to 3 d) were noted for BPA biodegradation in river waters regardless of geographic location, sampling site (i.e., upstream vs downstream of wastewater outfalls), sediment addition (< or = 0.05%), and initial test chemical concentration (50-5,500 microgram/L). Subsequent studies conducted at environmentally relevant concentrations (0.05 and 0.5 microgram/L) also indicated short half-lives (3-6 d) for BPA and support the extrapolation of the half-lives measured in this study over a wide range of environmental concentrations. The fact that BPA was degraded rapidly in surface waters taken from diverse locations in the United States and Europe as well as in studies recently conducted in Japan suggests that BPA degrading microorganisms are widely distributed in nature. These observations provide clear evidence that BPA is not persistent in the aquatic environment.

Aerobic biodegradation of dichloroethylenes in surface and subsurface soils.

Laboratory studies were conducted to examine the aerobic biodegradation of dichloroethylenes (cis-1,2-DCE, trans-1,2-DCE and 1,1-DCE) in soil and groundwater. Authentic surface and subsurface materials with no reported DCE exposure history were used. All DCE isomers were observed to biodegrade to varying degrees in the soils examined. Use of radiolabeled [14C] test chemicals allowed correlation of DCE disappearance with mineralization to 14CO2. Study results indicate that naturally occurring microorganisms in soil and groundwater are capable of degrading cis-1,2-, trans-1,2- and 1,1-DCE without laboratory supplementation of exogenous organic nutrients, or previous exposure history. The data further suggest that degradative potential may vary with soil type, DCE isomer structure, and concentration.

Molecular mapping of Alzheimer-type dementia in Down's syndrome.

Previous research has hypothesized an association between Alzheimer's disease and the amyloid precursor protein (APP) gene found on chromosome 21. We report the case of a 78-year-old woman with Down's syndrome with partial trisomy 21 [46,XX,rec(21)dup q, inv(21) (p12q22.1)]. No evidence of Alzheimer's disease was found on neuropsychological, magnetic resonance imaging, and neuropathological assessment. The gene sequence for APP was present in only two copies. This case further supports the hypothesis that Alzheimer's disease is associated with trisomy for proximal chromosome 21q, including the APP gene.

Filter ventilation and nicotine content of tobacco in cigarettes from Canada, the United Kingdom, and the United States.

OBJECTIVES: The purpose was to determine filter ventilation and the nicotine content of tobacco and their contribution to machine-smoked yields of cigarettes from the United States, Canada, and the United Kingdom. METHODS: Ninety-two brands of cigarettes (32 American, 23 Canadian, and 37 British brands) were purchased at retail outlets in State College, Pennsylvania, United States, Toronto, Canada, and London, United Kingdom. A FIDUS FDT filter ventilation tester measured the percentage air-dilution from filter vents. High-pressure, liquid chromatography was used to measure the nicotine content of tobacco. Regression techniques were used to examine the contributions of tobacco nicotine content and filter ventilation to machine-smoked yields of tar, nicotine, and carbon monoxide (CO). RESULTS: Ninety-four per cent of the American brands, 91% of the Canadian brands, and 79% of British brands were ventilated. The total nicotine content of tobacco and percent nicotine (by weight of tobacco) averaged 10.2 mg (standard error of the mean (SEM) 0.25, range: 7.2 to 13.4) and 1.5% (SEM 0.03, range 1.2 to 2) in the United States, 13.5 mg (SEM 0.49, range: 8.0 to 18.3) and 1.8% (SEM 0.06, range: 1.0 to 2.4) in Canada, 12.5 mg (SEM 0.33, range: 9 to 17.5) and 1.7% (SEM 0.04, range: 1.3 to 2.4) in the United Kingdom. Multiple regression analyses showed that ventilation was by far the largest factor influencing machine-smoked yields of tar, nicotine, and CO. CONCLUSION: Filter ventilation appears to be the predominant method for reducing machine-smoked yields of tar, nicotine, and CO in three countries. However, some brands contain about twice as much nicotine (total content or percent nicotine) as do others, indicating that tobacco types or blends and tobacco castings can be used to manipulate nicotine content and nicotine delivery of cigarettes.

A pilot study of concomitant boost accelerated superfractionated radiotherapy for stage III cancer of the uterine cervix.

PURPOSE: Retrospective studies suggest that prolonged treatment time adversely affects control rates of squamous carcinomas managed by radiotherapy. From 1989 to 1994 a prospective clinical trial was conducted to assess the feasibility and efficacy of concomitant boost accelerated superfractionated (CBASF) radiotherapy for advanced uterine cervical carcinoma. METHODS AND MATERIALS: Twenty newly diagnosed patients with FIGO stage III squamous cell carcinoma of the cervix were irradiated using a CBASF regimen. Patients received 45 Gy administered to the whole pelvis in 25 fractions in 5 weeks. On Monday, Wednesday, and Friday of the last 3 weeks, an additional 1.6 Gy boost was given 6 hours after the whole pelvis treatment. The 9 boost treatments, totaling 14.4 Gy, were given via lateral fields encompassing the parametria and primary tumor for a cumulative tumor dose of 59.4 Gy. A single low-dose rate brachytherapy procedure was performed within 1 week after the external beam radiotherapy to raise the point A dose to 85-90 Gy in 42 days. Primary endpoints of analysis were local control, complications, and patterns of failure. Results are compared with the outcomes of 21 patients treated with conventionally fractionated (CF) radiotherapy during the same years. RESULTS: Median total treatment time was 46 days in the CBASF group (range 37-62). Median follow-up interval among surviving CBASF patients is 3.8 years. The four-year actuarial local control rates are 78% and 70% in the CBASF and CF groups, respectively (p = ns). Only 2 CBASF patients required a treatment break because of acute toxicity, but severe late complications occurred in 8/20 CBASF patients for a crude rate of 40%. Distant failure was more common than local failure in the CBASF group, and para-aortic node failure occurred in six of the eight CBASF patients with distant failure. CONCLUSIONS: In the management of stage III cervix cancer, the CBASF regimen produced a trend toward improved local control when compared with the CF regimen, shifting the patterns of failure toward a higher rate of isolated distant failures. The high frequency of para-aortic node failure warrants consideration of elective treatment to this region in stage III patients treated with curative intent. Although the high local control rate of the CBASF regimen supports further investigation of accelerated treatment regimens for locally advanced cervix cancer, the unacceptable risk of late complications necessitates refinement in technique and scheduling to improve the therapeutic ratio.

A questionnaire survey of resuscitation equipment carried by general practitioners and their initial management of ventricular fibrillation.

BACKGROUND: The early defibrillation of patients having a cardiac arrest and who are in ventricular fibrillation has been shown to increase survival and is recommended by the European Resuscitation Council (ERC) and the American Heart Association. General practitioners (GPs) may expect to encounter a cardiac arrest in 5% of patients they attend who have a suspected acute myocardial infarction. AIM: To establish whether GPs on call were equipped to treat a patient in ventricular fibrillation, and to investigate their knowledge of the early stages of the current ERC guidelines for this cardiac rhythm. METHOD: A postal questionnaire was sent to all the 175 GPs who regularly admit patients to the West Suffolk Hospital. It asked for details of equipment and drugs carried when on call, recognition of a cardiac rhythm strip of ventricular fibrillation, and treatment to be given for this rhythm. RESULTS: A total of 105 replies were returned (representing a 60% response rate). The distribution of practice size and location reflected primary health care in this area. Fourteen GPs (13%) had attended an advanced cardiac life-support course at some time, and 44 (41.9%) had read the current ERC guidelines. The majority of GPs (60%) carried advanced airway management equipment to allow endotracheal intubation, but only 37 (35%) would have been able to administer additional oxygen. Again, most (82%) would have been able to establish intravenous access, but only 39% carried 2 mg or more of adrenaline, the only recommended drug in the initial stages of resuscitation from ventricular fibrillation. A defibrillator was carried by 37 GPs (35%) when on call, but out of these only 14 had an integral monitor screen and 3 were semi-automatic defibrillators. Ninety-five GPs (91%) successfully identified ventricular fibrillation, but only 32 (31%) were able to state correctly the initial recommended treatment, and only 17 (16%) were able to quote the first two stages of the ERC guidelines of treatment of ventricular fibrillation. However, 78 GPs (74%) would have provided treatment compatible with the guidelines by giving the patient a pre-cordial thump and two subsequent defibrillatory shocks, albeit perhaps at an incorrect energy level and only if a defibrillator was available. CONCLUSIONS: This study shows that the equipment carried by the majority of GPs in this area is inadequate to deal successfully with the victims of cardiac arrest, and that significant reliance is placed on the resources of the ambulance service. It would also appear that most GPs are not fully conversant with the current ERC guidelines. The ability of GPs to manage cardiac arrests could be enhanced by their attending courses to update their resuscitation skills, one example being the advanced life-support courses endorsed by the United Kingdom Resuscitation Council, and that the Royal College of General Practitioners could stimulate interest in this area by extending their requirement for candidates for the membership examination to include written documentation demonstrating proficiency at advanced life support, in addition to the current requirement for basic life support only.

Meta-analysis of chemotherapy regimens for ovarian carcinoma: a reassessment of cisplatin, cyclophosphamide and doxorubicin versus cisplatin and cyclophosphamide.

OBJECTIVE: To compare three year survival, median survival and improved longevity with the addition of doxorubicin to a chemotherapy regimen of cisplatin and cyclophosphamide used in the treatment of ovarian cancer and to integrate this with a previous meta-analysis that compared three year survival. METHODS: Twenty-three studies that evaluated either the control or test arms were combined for meta-analysis. Five studies were randomized with both arms. Inclusion criteria consisted of median survival data, three year survival data, no previous chemotherapy or radiation and adequate follow-up. The data were analyzed with a twotailed t test, a fixed effects odds ratio, a random effects odds ratio, logistic regression modeling for three year survival and standard regression modeling for median survival. RESULTS: A statistically significant improvement in three year survival was demonstrated with the fixed effects odds ratio analysis combining the five prospective randomized studies and with logistic regression model of all the studies. Random effects odds ratio and the two-tailed t test failed to show statistical significance. Standard regression modeling demonstrated statistically significant improvement in median survival for a doxorubicin dose intensity of 40 mg/m2 and near significance for a doxorubicin dose intensity of 50 mg/m2. Median survival was improved by 1.91 months with the addition of doxorubicin to the cisplatin/cyclophosphamide regimen. CONCLUSION: Although there appears to be statistically significant improvement in three year survival and median survival with the addition of doxorubicin to the cisplatin/cyclophosphamide regimen for ovarian cancer, the actual improvement in median survival is less than two months and therefore, the added toxicity of doxorubicin may not be warranted.

Radiological intervention in Budd-Chiari syndrome: techniques and outcome in 18 patients.

We reviewed our experience of the therapeutic role of radiology in Budd-Chiari syndrome. Patients with stenosis and/or occlusion of the main hepatic veins and/or inferior vena cava (IVC) are suitable for radiological intervention (35% in our series). Eighteen patients (mean age 37.4 years) have undergone radiological intervention over the past 8 years. The site of obstruction was the hepatic veins in 12/18 patients while 6/18 patients had both hepatic vein and IVC obstruction, which in two was due to tumour thrombus. One patient had repeated dilatations of a mesocaval shunt; 49 angiographic venous dilatations were performed (18 during initial intervention, 31 on review) including 10 recanalizations of occlusions. A combined transhepatic-transjugular approach was used for 10/49 procedures. Thrombolysis was performed in 5/18 and stent insertion in 6/18 patients. Three serious complications occurred (IVC stent migration, hepatic artery pseudoaneurysm, myocardial puncture). Follow-up, after initial intervention, has continued for a mean of 24.2 months (range 4 days-92 months). Symptoms related to hepatic venous outflow obstruction were fully relieved in 10/18 (56%) patients and partially relieved in 4/18 (22%) patients. Close monitoring (and re-intervention) during the early post-intervention period is needed because 28% of initial venous dilatations failed to provide adequate venous return in the first instance. Once the patient is stabilized regular review is mandatory as HV restenosis is common after 10 months or more follow-up. The efficacy and safety of radiological intervention make it the preferred first line of treatment in selected patients with Budd-Chiari syndrome.

Ectasia of the vertebral artery as a cause of isolated pyramidal tract signs: case report and a review of the literature.

A rare presentation of vertebral artery ectasia is reported with magnetic resonance imaging and angiographic correlation. The unusually low level of the abnormality had previously resulted in an incorrect diagnosis of primary pyramidal degeneration. One similar case has been reported in the world literature.