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Selected AbstractsAre antidepressants safe in the treatment of bipolar depression?ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2008A critical evaluation of their potential risk to induce switch into mania or cycle acceleration Objective:, To address whether switch of depression into hypomania or mania or cycle acceleration in patients with bipolar disorder is caused by antidepressants or whether this phenomenon is attributable to the natural history of bipolar disorder itself. Method:, A critical review of the literature, pointing at sources of bias that have been previously overlooked. For examining the causation in question, the Bradford,Hill criteria were applied, i.e. specificity of the potential causative agent, strength of effect, consistency in findings, dose,response relation, temporal relation with exposure to agent preceding effect and biological plausibility. Results:, There is a scarcity of randomized studies addressing the question, and the available studies all suffer from various forms of bias. However, there is some evidence suggesting that antidepressants given in addition to a mood stabilizer are not associated with an increased rate of switch when compared with the rate associated with the mood stabilizer alone. Conclusion:, When combined with a mood stabilizer, antidepressants given for acute bipolar depression seemingly do not induce a switch into hypomania or mania. Whether antidepressants may accelerate episode frequency and/or may cause other forms of destabilization in patients with bipolar disorder remain to be properly studied. [source] Experimental evolution of dispersal in spatiotemporally variable microcosmsECOLOGY LETTERS, Issue 10 2003Nicholas A. Friedenberg Abstract The world is an uncertain place. Individuals' fates vary from place to place and from time to time. Natural selection in unpredictable environments should favour individuals that hedge their bets by dispersing offspring. I confirm this basic prediction using Caenorhabditis elegans in experimental microcosms. My results agree with evolutionary models and correlations found previously between habitat stability and individual dispersal propensity in nature. However, I also find that environmental variation that triggers conditional dispersal behaviour may not impose selection on baseline dispersal rates. These findings imply that an increased rate of disturbance in natural systems has the potential to cause an evolutionary response in the life history of impacted organisms. [source] What is the nature of the emergence phenomenon when using intravenous or intramuscular ketamine for paediatric procedural sedation?EMERGENCY MEDICINE AUSTRALASIA, Issue 4 2009Greg Treston Abstract Objective: Ketamine has become the drug most favoured by emergency physicians for sedation of children in the ED. Some emergency physicians do not use ketamine for paediatric procedural sedation (PPS) because of concern about emergence delirium on recovery. The present study set out to determine the true incidence and nature of this phenomenon. Methods: Prospective data relating to any emergence agitation, crying, hallucinations, dreams, altered perceptions, delirium and necessary interventions were recorded in consecutive cases of ketamine PPS from March 2002 to June 2007, and analysed. Standard inclusion and exclusion criteria for the use of ketamine were followed. Results: A total of 745 prospective data collection records were available for analysis over the 5 year period. Of all, 93 (12.5%) children cried on awakening when recovering from PPS, 291 (39%) experienced pleasant altered perceptions and 16 (2.1%) experienced what was called ,emergence delirium'. None required any active treatment and all except one settled within 20 min. There was no evidence of an increased rate of nightmares on telephone follow up in the weeks post procedure. Conclusion: The belief that ketamine, in the doses used for ED PPS, causes frequent emergence delirium is flawed. A pleasant emergence phenomenon is common, but is not distressing for the child, and has no long-term (up to 30 days) negative sequelae. Rarely, there is anxiety or distress on awakening from ketamine sedation, which settles spontaneously. This should not deter emergency physicians from using ketamine for PPS. [source] Isolation and characterization of naphthalene-degrading bacteria from sediments of Cadiz area (SW Spain)ENVIRONMENTAL TOXICOLOGY, Issue 5 2008D. Nair Abstract Petroleum hydrocarbon contamination of harbor sediments from shipping activity, fuel oil spills, and runoffs are becoming a great concern because of the toxicity and recalcitrance of many of the fuel components. Polycyclic aromatic hydrocarbons (PAHs) are of most concern due to their toxicity, low volatility, resistance to degradation, and high affinity for sediments. Microorganisms, especially bacteria, play an important role in the biodegradation of these hydrocarbons. The objective of the present study was to characterize and isolate PAH-(naphthalene) degrading bacteria in the coastal sediments of Cadiz (SW Spain), since this area is mostly polluted by PAH occurrence. A total of 16 naphthalene-utilizing bacteria were isolated from these sites. Introduction of bacteria isolated from contaminated sediments into mineral medium contributed to the increased rate of hydrocarbon utilization. The bacterial isolates obtained from these sites are very potent in utilizing naphthalene and crude oil. It would be interesting to assess if the selected naphthalene-degrading isolates may degrade other compounds of similar structure. Hence these isolates could be very helpful in bioremediating the PAH-contaminated sites. Further pursue on this work might represent eco-friendly solution for oil contamination on sea surface and coastal area. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008. [source] Electroconvulsive seizure thresholds and kindling acquisition rates are altered in mouse models of human KCNQ2 and KCNQ3 mutations for benign familial neonatal convulsionsEPILEPSIA, Issue 7 2009James F. Otto Summary Purpose:, Benign familial neonatal convulsions (BFNC) is caused by mutations in the KCNQ2 and KCNQ3 genes, which encode subunits of the M-type potassium channel. The purpose of this study was to examine the effects of orthologous BFNC-causing mutations on seizure thresholds and the acquisition of corneal kindling in mice with heterozygous expression of the mutations. Methods:, The effects of the Kcnq2 gene A306T mutation and the Kcnq3 gene G311V mutation were determined for minimal clonic, minimal tonic hindlimb extension, and partial psychomotor seizures. The rate of corneal kindling acquisition was also determined for Kcnq2 A306T and Kcnq3 G311V mice. Results:, Seizure thresholds were significantly altered relative to wild-type animals in the minimal clonic, minimal tonic hindlimb extension, and partial psychomotor seizure models. Differences in seizure threshold were found to be dependent on the mutation expressed, the seizure testing paradigm, the genetic background strain, and the gender of the animal. Mutations in Kcnq2 and Kcnq3 were associated with an increased rate of corneal kindling. In the Kcnq2 A306T mice, an increased incidence of death occurred during and immediately following the conclusion of the kindling acquisition period. Conclusions:, These results suggest that genetic alterations in the subunits that underlie the M-current and cause BFNC alter seizure susceptibility in a sex-, mouse strain-, and seizure-test dependent manner. Although the heterozygous mice do not appear to have spontaneous seizures, the increased seizure susceptibility and incidence of death during and after kindling suggests that these mutations lead to altered excitability in these animals. [source] Cerebral Damage in Epilepsy: A Population-based Longitudinal Quantitative MRI StudyEPILEPSIA, Issue 9 2005Rebecca S. N. Liu Summary:,Purpose: Whether cerebral damage results from epileptic seizures remains a contentious issue. We report on the first longitudinal community-based quantitative magnetic resonance imaging (MRI) study to investigate the effect of seizures on the hippocampus, cerebellum, and neocortex. Methods: One hundred seventy-nine patients with epilepsy (66 temporal lobe epilepsy, 51 extratemporal partial epilepsy, and 62 generalized epilepsy) and 90 control subjects underwent two MRI brain scans 3.5 years apart. Automated and manual measurement techniques identified changes in global and regional brain volumes and hippocampal T2 relaxation times. Results: Baseline hippocampal volumes were significantly reduced in patients with temporal lobe epilepsy and could be attributed to an antecedent neurologic insult. Rates of hippocampal, cerebral, and cerebellar atrophy were not syndrome specific and were similar in control and patient groups. Global and regional brain atrophy was determined primarily by age. A prior neurologic insult was associated with reduced hippocampal and cerebellar volumes and an increased rate of cerebellar atrophy. Significant atrophy of the hippocampus, neocortex, or cerebellum occurred in 17% of patients compared with 6.7% of control subjects. Patients with and without significant volume reduction were comparable in terms of seizure frequency, antiepileptic drug (AED) use, and epilepsy duration, with no identifiable risk factors for the development of atrophy. Conclusions: Overt structural cerebral damage is not an inevitable consequence of epileptic seizures. In general, brain volume reduction in epilepsy is the cumulative effect of an initial precipitating injury and age-related cerebral atrophy. Significant atrophy developed in individual patients, particularly those with temporal lobe and generalized epilepsy. Longer periods of observation may detect more subtle effects of seizures. [source] High-frequency Oscillations after Status Epilepticus: Epileptogenesis and Seizure GenesisEPILEPSIA, Issue 9 2004Anatol Bragin Summary:,Purpose: To investigate the temporal relation between high-frequency oscillations (HFOs) in the dentate gyrus and recurrent spontaneous seizures after intrahippocampal kainite-induced status epilepticus. Methods: Recording microelectrodes were implanted bilaterally in different regions of hippocampus and entorhinal cortex. A guide cannula for microinjection of kainic acid (KA) was implanted above the right posterior CA3 area of hippocampus. After recording baseline electrical activity, KA (0.4 ,g/0.2 ,l) was injected. Beginning on the next day, electrographic activity was recorded with video monitoring for seizures every day for 8 h/day for ,30 days. Results: Of the 26 rats studied, 19 revealed the appearance of sharp-wave activity and HFOs in the frequency range of 80 to 500 Hz in the dentate gyrus ipsilateral to the KA injection. In the remaining seven rats, no appreciable activity was noted in this frequency range. In some rats with recurrent seizures, HFOs were in the ripple frequency range (100,200 Hz); in others, HFOs were in the fast ripple frequency range (200,500 Hz), or a mixture of both oscillation frequencies was found. The time of detection of the first HFOs after status epilepticus varied between 1 and 30 days, with a mean of 6.3 ± 2.0 (SEM). Of the 19 rats in which HFO activity appeared, all later developed recurrent spontaneous seizures, whereas none of the rats without HFOs developed seizures. The sooner HFO activity was detected after status epilepticus, the sooner the first spontaneous seizure occurred. A significant inverse relation was found between the time to the first HFO detection and the subsequent rate of spontaneous seizures. Conclusions: A strong correlation was found between a decreased time to detection of HFOs and an increased rate of spontaneous seizures, as well as with a decrease in the duration of the latent period between KA injection and the detection of spontaneous seizures. Two types of HFOs were found after KA injection, one in the frequency range of 100 to 200 Hz, and the other, in the frequency range of 200 to 500 Hz, and both should be considered pathological, suggesting that both are epileptogenic. [source] An epidemiological study of risk factors associated with the recurrence of equine grass sickness (dysautonomia) on previously affected premisesEQUINE VETERINARY JOURNAL, Issue 2 2004J. R. Newton Summary Reasons for performing study: The reasons why equine grass sickness (EGS) recurs on premises are unknown and, consequently, practical methods for reducing the risk of recurrence are not available. Objectives: To identify risk factors associated with recurrence of EGS on premises and to gain possible insights into the pathogenesis of the disease. Methods: Data on disease history and risk factors were collected by postal questionnaire from premises with EGS cases between 1st January 1997 and 31st December 2001. Data on variation in rates of recurrence of EGS for different risk factors were analysed using Poisson regression analysis. Results: Of 509 premises contacted, 305 (60%) returned useable questionnaires and 100 of these (33%) were classified as ,recurrent' premises. An overall median incidence rate for EGS of 2.1 EGS incidents/100 horses/premises/year was recorded. There was an increased rate of recurrence with higher numbers of horses, presence of younger animals, stud farms and livery/riding establishments, loam and sand soils, rearing of domestic birds and mechanical droppings removal. The rate of recurrence decreased with chalk soil, cograzing ruminants, grass cutting on pastures and removal of droppings by hand. Several statistically significant interactions were identified. Conclusions: Many of the findings are consistent with the theory that EGS is a toxico-infectious form of botulism. Several of the significant factors identified may directly or indirectly relate to soil disturbance and consequent soil contamination of grass, thereby increasing the rate of exposure of grazing horses to Clostridium botulinum, which resides in soil. Potential relevance: Identification of potentially modifiable risk factors may, ideally following validation in appropriately designed, controlled and randomised intervention studies, lead to practical measures to reduce the incidence of EGS on previously affected premises. [source] Impaired nutritional status in common variable immunodeficiency patients correlates with reduced levels of serum IgA and of circulating CD4+ T lymphocytesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2001M. Muscaritoli Background Common variable immunodeficiency (CVI) is a primary defect of the immune system. Infections, persistent diarrhoea and malabsorption may result in malnutrition, which may in turn contribute to increased morbidity. In this paper, the prevalence of malnutrition in CVI was evaluated. Patients and methods Forty CVI patients (20 male, 20 female, aged 17,75 years) underwent anthropometric measurements from which body mass index, arm fat and muscle area were calculated. Body mass index values <,18·5 and arm fat and muscle area values <,10th percentile were considered indicative of malnutrition. Patients were divided into four groups according to circulating CD4+ T cells (lower or greater than 300 µL,1) and serum immunoglobulin A (IgA) levels (detectable and undetectable). Results Body mass index <,18·5, arm fat and muscle area <,10th percentile were observed in 23%, 58% and 44%, respectively, of patients. Lower values of body mass index, arm fat and muscle area were more frequent in patients with low CD4+ cells and undetectable IgA. Low arm fat values were more frequent in patients with diarrhoea (P = 0·03). Infectious episodes were more frequent in undetectable IgA than in detectable IgA patients (P = 0·04). Conclusions Anthropometric measurements revealed an increased rate of malnutrition in CVI patients, particularly in those with low CD4+ and undetectable IgA, suggesting that selected CVI subjects could be considered for standard or specialized nutritional support. [source] PRECLINICAL STUDY: FULL ARTICLE: Repeated ethanol administration modifies the temporal structure of sucrose intake patterns in mice: effects associated with behavioral sensitizationADDICTION BIOLOGY, Issue 3 2010Raúl Pastor ABSTRACT Neuroadaptations supporting behavioral sensitization to abused drugs are suggested to underlie pathological, excessive motivation toward drugs and drug-associated stimuli. Drug-induced sensitization has also been linked to increased appetitive responses for non-drug, natural reinforcers. The present research investigated whether ethanol (EtOH)-induced neural changes, inferred from psychomotor sensitization, can modify consumption and intake dynamics for the natural reinforcer, sucrose. The effects of EtOH-induced sensitization in mice on the temporal structure of sucrose intake patterns were measured using a lickometer system. After sensitization, sucrose intake dynamics were measured for 1 hour daily for 7 days and indicated more rapid initial approach and consumption of sucrose in EtOH-sensitized groups; animals showed a shorter latency to the first intake bout and an increased number of sucrose bottle licks during the initial 15 minutes of the 1-hour sessions. This effect was associated with increased frequency and size of bouts. For the total 1-hour session, sucrose intake and bout dynamics were not different between groups, indicating a change in patterns of sucrose intake but not total consumption. When sensitization was prevented by the ,-aminobutyric acid B receptor agonist, baclofen, the increased rate of approach and consumption of sucrose were also prevented. Thus, EtOH-induced sensitization, and not the mere exposure to EtOH, was associated with changes in sucrose intake patterns. These data are consistent with current literature suggesting an enhancing effect of drug-induced sensitization on motivational processes involved in reinforcement. [source] Depletion of immature B,cells during Trypanosoma cruzi infection: involvement of myeloid cells and the cyclooxygenase pathwayEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2005Elina Zuniga Abstract The ability of a microorganism to elicit or evade B,cell responses represents a determinant factor for the final outcome of an infection. Although pathogens may subvert humoral responses at different stages of B,cell development, most studies addressing the impact of an infection on the B,cell compartment have focused on mature B,cells within peripheral lymphoid organs. Herein, we report that a protozoan infection, i.e. a Trypanosoma cruzi infection, induces a marked loss of immature B,cells in the BM, which also compromises recently emigrated B,cells in the periphery. The depletion of BM immature B,cells is associated with an increased rate of apoptosis mediated by a parasite-indirect mechanism in a Fas/FasL-independent fashion. Finally, we demonstrated that myeloid cells play an important role in B,cell depletion, since CD11b+ BM cells from infected mice secrete a product of the cyclooxygenase pathway that eliminates immature B,cells. These results highlight a previously unrecognized maneuver used by a protozoan parasite to disable B,cell generation, limiting host defense and favoring its chronic establishment. [source] Effectiveness of a community-based 3-year advisory program after acquired brain injuryEUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2007E. Grill Objective of this study was to examine the effectiveness of a coordinated, community based 3-year advisory program in 1534 patients with acquired brain injury. Patients and caregivers were offered a coordinated advisory program after discharge from rehabilitation. Patients in the historical control group received standard aftercare. The main outcomes were functional status [Functional Independence Measure (FIM)], and days spent in the acute hospital. The secondary outcome was survival. Patients were comparable for sex (intervention: 41.3% female, control: 38.0%), and younger in the control group (mean age intervention: 55.3, control: 49.6). Functional status at discharge was lower in the intervention group (mean FIM intervention: 66.2, control: 80.3). Patients in the intervention group experienced a moderate gain in FIM. Rate of days in hospital was 15.4 per 1000 person days (intervention) and 15.5 per 1000 person days (control). Patients of the intervention group had an increased rate of days in hospital. A total of 16.0% of patients in the intervention group and 19.3% in the control group died during follow-up. Patients in the intervention had a significant lower mortality risk depending on follow-up period and discharge FIM. The advisory program may be effective for all patients with acquired brain injury. [source] The A-subunit of surface-bound Shiga toxin stimulates clathrin-dependent uptake of the toxinFEBS JOURNAL, Issue 16 2005Maria L. Torgersen Shiga toxin can be internalized by clathrin-dependent endocytosis in different cell lines, although it binds specifically to the glycosphingolipid Gb3. It has been demonstrated previously that the toxin can induce recruitment of the toxin,receptor complex to clathrin-coated pits, but whether this process is concentration-dependent or which part of the toxin molecule is involved in this process, have so far been unresolved issues. In this article, we show that the rate of Shiga toxin uptake is dependent on the toxin concentration in several cell lines [HEp-2, HeLa, Vero and baby hamster kidney (BHK)], and that the increased rate observed at higher concentrations is strictly dependent on the presence of the A-subunit of cell surface-bound toxin. Surface-bound B-subunit has no stimulatory effect. Furthermore, this increase in toxin endocytosis is dependent on functional clathrin, as it did not occur in BHK cells after induction of antisense to clathrin heavy chain, thereby blocking clathrin-dependent endocytosis. By immunofluorescence, we show that there is an increased colocalization between Alexa-labeled Shiga toxin and Cy5-labeled transferrin in HeLa cells upon addition of unlabeled toxin. In conclusion, the data indicate that the Shiga toxin A-subunit of cell surface-bound toxin stimulates clathrin-dependent uptake of the toxin. Possible explanations for this phenomenon are discussed. [source] Undulatory fish swimming: from muscles to flowFISH AND FISHERIES, Issue 2 2006Ulrike K. Müller Abstract Undulatory swimming is employed by many fish for routine swimming and extended sprints. In this biomechanical review, we address two questions: (i) how the fish's axial muscles power swimming; and (ii) how the fish's body and fins generate thrust. Fish have adapted the morphology of their axial musculature for high power output and efficiency. All but the superficial muscle fibres are arranged along curved trajectories, and the myomeres form nested cones. Two conflicting performance goals shape the fibre trajectories of the axial muscles. Maximum power output requires that all fibres contract uniformly. In a bending fish, uniform contraction in a single myomere can be ensured by curved fibre trajectories. However, uniform strain is only desirable if all muscle fibres have the same contractile properties. The fish needs several muscle-fibre types that generate maximum power at different contraction speeds to ensure effective muscle power generation across a range of swimming speeds. Consequently, these different muscle-fibre types are better served by non-uniform contractions. High power output at a range of swimming speeds requires that muscle fibres with the same contractile properties contract uniformly. The ensuing helical fibre trajectories require cone-shaped myomeres to reduce wasteful internal deformation of the entire muscle when it contracts. It can be shown that the cone-shaped myomeres of fish can be explained by two design criteria: uniform contraction (uniform strain hypothesis) and minimal internal deformation (mechanical stability hypothesis). So far, only the latter hypothesis has found strong support. The contracting muscle causes the fish body to undulate. These body undulations interact with the surrounding water to generate thrust. The resulting flow behind the swimming fish forms vortex rings, whose arrangement reflects the fish's swimming performance. Anguilliform swimmers shed individual vortex rings during steady swimming. Carangiform swimmers shed a connected chain of vortex rings. The currently available sections through the total flow fields are often not an honest representation of the total momentum in the water , the wake of carangiform swimmers shows a net backward momentum without the fish accelerating , suggesting that our current picture of the generated flow is incomplete. To accelerate, undulatory swimmers decrease the angle of the vortex rings with the mean path of motion, which is consistent with an increased rate of backward momentum transfer. Carangiform swimmers also enlarge their vortex rings to accelerate and to swim at a higher speed, while eel, which are anguilliform swimmers, shed stronger vortex rings. [source] Enhanced exoenzyme activities in sediments in the presence of deposit-feeding Chironomus riparius larvaeFRESHWATER BIOLOGY, Issue 9 2007PETER STIEFArticle first published online: 10 JUN 200 Summary 1. The combined effects of deposit-feeding, bioturbation and bioirrigation by benthic macrofauna on the enzymatic hydrolysis of organic matter were studied in microcosms. Chironomus riparius larvae (Insecta, Diptera) served as model macrofauna and stinging nettle leaves (Urtica dioica) were used as a detrital food source. 2. In the upper 10 mm of the sediment (the habitat of C. riparius larvae), the activities of several exoenzymes, the contents of several fractions of particulate organic matter (POM), and the concentrations of dissolved oxidants (O2, NO) were measured on a small scale. Fluorescent particles (luminophores) were used to quantify the vertical redistribution of particles within the same layer. 3. In control sediment, the addition of detrital food enhanced exoenzyme activities in the 0,2 mm layer only. In the presence of C. riparius larvae, exoenzyme activities increased to 10 mm depth. Further, the content of POM in the 0,2 mm layer was lower in the presence than in the absence of larvae, suggesting ingestion and subduction of the added detritus. After prolonged incubation without further food addition, exoenzyme activities returned close to background values in both treatments, whereas the vertical distribution of POM remained unchanged. 4. The overall penetration depth of O2 and NO into the sediment was greater in the presence than the absence of C. riparius, the differences being more pronounced after prolonged incubation. Locally high O2 and NO concentrations due to bioirrigation by C. riparius were measured deep in the sediment. Net downward transport of particles was observed only in the presence of C. riparius larvae and only at the beginning of the incubation. 5. I conclude that deposit-feeding and bioturbation by macrofauna can quickly remove freshly deposited POM from the sediment surface and transfer it to less oxygenated sites (i.e. animal guts and deep sediment layers). Bioirrigation also increases the availability of oxidants deep in the sediment. The oscillation of oxidant supply to POM particles by ingestion,egestion, burial and re-burial, and the intermittent bioirrigation of subsurface sediment, is probably the cause of the increased rate of organic matter hydrolysis, the rate-limiting step in mineralization. [source] Familial loading in specific language impairment: patterns of differences across proband characteristics, gender and relative typeGENES, BRAIN AND BEHAVIOR, Issue 3 2007G. Conti-Ramsden There is now little doubt that both environmental factors and genes are likely to make important contributions to the aetiology of specific language impairment (SLI). The most commonly proposed model for understanding these influences is the multifactorial model. In the present study we examine two expectations based on this model: that there will be a systematic relationship between the severity of proband language scores and the rate and severity of SLI in relatives and that relatives will be more strongly affected if they are relatives of a proband of the more rarely affected gender (female) because the latter require a higher genetic liability to become equally impaired. Ninety-three probands and their 300 first-degree relatives participated in this study. Results showed a relationship between proband severity at age 14 and an increased rate of SLI in relatives. This relationship was strong for child siblings and was significant with respect to both rate of SLI and severity over a range of language and literacy measures. In contrast, higher levels of SLI among relatives of female rather than male probands was entirely disproved. [source] The beverage maté: A risk factor for cancer of the head and neckHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2003David Goldenberg MD Abstract Background. Maté is a tealike beverage consumed habitually in South America and among South Americans throughout the world. It is brewed from the dried leaves and stemlets of the perennial tree Ilex paraguariensis (yerba maté), a species that belongs to the Aquifoliaceae family. Maté consumption has been associated with an increased rate of oral, oropharyngeal, esophageal, and laryngeal cancers. The purpose of this study is to review the literature and discuss the role of Maté consumption as a risk factor for head and neck cancers. Materials and Methods. We performed a thorough review of the relevant literature linking maté consumption with head and neck cancer and the proposed carcinogenicity of maté. Case control studies on maté-drinking populations and in vivo and in vitro studies on the carcinogenicity of maté were reviewed. The populations included in many of these studies also used alcohol and tobacco products, confounding the influence of maté as an independent risk factor. Results. Evidence in the literature suggests that maté consumption is carcinogenic and plays a role in the development of cancers of the oral cavity, pharynx, larynx, and esophagus. Conclusions. The exact mechanism of carcinogenesis of maté is unknown. Both chemical and thermal carcinogenesis mechanisms have been suggested. Available information suggests that maté drinking is a risk factor for upper aerodigestive tract cancer. © 2003 Wiley Periodicals, Inc. Head Neck 25: 595,601, 2003 [source] Laparoscopic cholecystectomy in the grossly obese: 4 years experience and review of literatureHPB, Issue 4 2002M Hussien Background Conventional abdominal surgery in grossly obese patients is associated with an increased rate of postoperative complications; thus, laparoscopic surgery may be preferred in these patients. Patients and methods A prospective analysis was performed of 20 grossly obese patients who underwent laparoscopic cholecystectomy between April 1996 and April 2000 for symptomatic non-complicated gallstone disease. Results Technical problems at operation included difficulty with induction of pneumoperitoneum and introduction of the most lateral subcostal port, retraction of the gallbladder fundus, the need for longer instruments and the closure of the fascia. Laparoscopic cholecystectomy was successfully completed in 19 patients, but one patient required conversion to open operation. There were no anaesthetic difficulties. Two patients developed minor chest infections. The mean hospital stay was 2.9 days. Conclusion Laparoscopic cholecystectomy is feasible and can be recommended for symptomatic gallstone disease in grossly obese patients. [source] Azathioprine or 6-mercaptopurine before colectomy for ulcerative colitis is not associated with increased postoperative complicationsINFLAMMATORY BOWEL DISEASES, Issue 5 2002Uma Mahadevan Abstract Aim To determine whether the use of azathioprine/6-mercaptopurine before colectomy is associated with an increased rate of postoperative complications. Methods All patients who underwent colectomy with ileal pouch,anal anastomosis for ulcerative colitis between 1997 and 1999 were identified. Medical records were abstracted for demographics, extent and duration of disease, dose and duration of corticosteroids and azathioprine/6-mercaptopurine, albumin, and Truelove/Witts score. Early (30-day) and late (6-month) complications were identified. Noncorticosteroid immunosuppressive use was coded as none, azathioprine/6-mercaptopurine within 1 week of surgery, or therapy with other immunosuppressive agents within 1 month of surgery. A logistic regression analysis assessed the association between these variables and complications. Results Early complications occurred in 49 of 151 (32%) patients not treated with immunosuppressive agents, 12 of 46 (26%) azathioprine/6-mercaptopurine-treated patients, and 4 of 12 (33%) patients treated with other immunosuppressive agents (p = 0.71). Late complications occurred in 72 of 148 (49%), 20 of 46 (43%), and 8 of 12 (67%) patients in these same groups, respectively. Intravenous or oral steroids at doses of 40 mg/d or greater (p < 0.01) and severe or fulminant disease (p = 0.0094) were associated with greater early complication rates. Conclusion Early complications after restorative proctocolectomy for ulcerative colitis are associated with high dose steroids and severe disease but not use of azathioprine/6-mercaptopurine. [source] On the dynamics of breast tumor development in women carrying germline BRCA1 and BRCA2 mutationsINTERNATIONAL JOURNAL OF CANCER, Issue 8 2008Richard Simon Abstract We used mathematical models to analyze the age-incidence curve of breast carcinoma for individuals carrying a germline mutation in the BRCA1 or BRCA2 gene locus. Although many genomic abnormalities have been identified in breast tumors, we found that a two-stage model fit the data well. A one-hit model was not, however, consistent with the data. The results supported the hypothesis that the first hit represents loss of the wild type BRCA1 or BRCA2 allele as this occurs at a rate very similar to that for loss of the wild-type RB allele in retinoblastoma. Loss of the wild-type BRCA1 or BRCA2 allele appears to destabilize the genome as the second event occurs at a much higher rate. The second event is "rate limiting" in the sense that its occurrence is constrained by the limited number of intermediate cells with doubly mutated BRCA1 or BRCA2 alleles. The second event may not be unique, however. Loss of the wild-type BRCA allele appears to result in an increased rate for subsequent genomic events. A second event increasing proliferation of the partially malignant intermediate clone may lead inexorably to production and selection of cells with additional mutations in genes that facilitate tumor progression. © 2007 Wiley-Liss, Inc. [source] The increased expression of Y box-binding protein 1 in melanoma stimulates proliferation and tumor invasion, antagonizes apoptosis and enhances chemoresistanceINTERNATIONAL JOURNAL OF CANCER, Issue 10 2007Birgit Schittek Abstract In previous studies we identified the transcription/translation factor Y-box-binding protein (YB-1) as a gene that is upregulated in primary melanoma and melanoma metastases when compared to benign melanocytic nevi. To analyze whether YB-1 expression correlates with melanoma progression in vitro and in vivo, we performed expression analysis on melanoma cell lines representing different stages of melanoma progression and on tissues of melanocytic nevi, primary melanoma and melanoma metastases. Our data indicate that compared to benign melanocytes YB-1 expression is increased in melanoma cells in vitro and in vivo and that YB-1 is translocated into the nucleus in invasive and metastatic melanoma cells. To reveal the functional role of YB-1 in melanoma progression we achieved a stable downregulation of YB-1 using shRNA in metastatic melanoma cells. Interestingly, YB-1 downregulation resulted in a pronounced reduced rate of proliferation and an increased rate of apoptotic cell death. In addition, migration and invasion of melanoma cells in monolayer and in a three-dimensional skin reconstruct in vitro was significantly reduced. These effects were accompanied by downregulation of genes involved in proliferation, survival and migration/invasion of melanoma cells such as MMP-2, bcl-2, Cyclin D1, p53 and p16INK4A. Furthermore, melanoma cells with a reduced YB-1 expression showed a decreased resistance to the chemotherapeutic agents cisplatin and etoposide. These data suggest that YB-1 is involved in malignant transformation of melanocytes and contributes to the stimulation of proliferation, tumor invasion, survival and chemoresistance. Thus, YB-1 may be a promising molecular target in melanoma therapy. © 2007 Wiley-Liss, Inc. [source] MRP1 and glucosylceramide are coordinately over expressed and enriched in rafts during multidrug resistance acquisition in colon cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 4 2004Karin Klappe Abstract Previously we have described a novel multidrug-resistant cell line, HT29col, which displayed over expression of the multidrug-resistance protein 1 (MRP1) and an altered sphingolipid composition, including enhanced levels of glucosylceramide (GlcCer; Kok JW, Veldman RJ, Klappe K, Koning H, Filipeanu C, Muller M. Int J Cancer 2000;87:172,8). In our study, long-term screening revealed that, during colchicine-induced acquisition of multidrug resistance in a new HT29col cell line, increases in GlcCer occurred concomitantly with upregulation of MRP1 expression. Both MRP1 and GlcCer were found enriched in Lubrol-insoluble membrane domains. The expression of MRP1 and GlcCer were tightly correlated, as indicated also by a reversal of both at the later stage of colchicine consolidation. Resistance to colchicine was determined by MRP1, while glucosylceramide synthase (GCS) did not contribute: 1) Resistance was fully inhibited by MK571. 2) GCS expression and activity were not upregulated in HT29col cells. 3) Inhibition of GCS did not affect MRP1-mediated efflux function or sensitivity to colchicine. Instead, overall sphingolipid metabolism was upregulated through an increased rate of ceramide biosynthesis. In conclusion, upregulation of MRP1 occurs in concert with upregulation of GlcCer during multidrug-resistance acquisition, and both are enriched in rafts. The increased GlcCer pool does not directly modulate MRP1 function and cell survival. © 2004 Wiley-Liss, Inc. [source] UVB phototherapy and skin cancer risk: a review of the literatureINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2005Ernest Lee MD Background, UVB phototherapy is a common treatment modality for psoriasis and other skin diseases. Although UVB has been in use for many decades, many clinicians are hesitant to use this type of phototherapy because of concern over increasing the skin cancer risk. Over the past 20 years, numerous studies have been published examining this issue, but a consensus or analysis of the skin cancer risk is required for the dermatologist to make an educated risk,benefit analysis. Objective, To assess the risk of skin cancer associated with UVB phototherapy. Methods, All prospective or retrospective studies were identified in MEDLINE from 1966 to June 2002. Bibliographies were searched to identify any additional studies examining this issue. All studies that attempted to quantify or qualify any additional skin cancer risk from UVB phototherapy were included. Study selection was performed by two independent reviewers. Results, Eleven studies (10 of which concerned psoriasis patients), involving approximately 3400 participants, were included. Of note, three of the studies involved the same cohort: members of the 16-center US Psoralen plus UVA (PUVA) Follow-up Study. Other than the most recent Finnish study, all studies eventually showed no increased skin cancer risk with UVB phototherapy. One of the PUVA cohort studies examined genital skin cancers, and found an increased rate of genital tumors associated with UVB phototherapy, although this study has not been duplicated. Conclusion, The evidence suggests that UVB phototherapy remains a very safe treatment modality. [source] Stent-protected angioplasty in asymptomatic carotid artery stenosis vs. endarterectomy: SPACE2 , a three-arm randomised-controlled clinical trialINTERNATIONAL JOURNAL OF STROKE, Issue 4 2009T. Reiff Moderate to severe (,70%) asymptomatic stenosis of the extracranial carotid artery leads to an increased rate of stroke of approximately 11% in 5 years. Patients with asymptomatic carotid stenosis, however, are also at a higher risk of nonstroke vascular events. The estimated annual risks of such events in patients with asymptomatic stenosis are 7% for a coronary ischaemic event and 4,7% for overall mortality. The superiority of carotid endarterectomy compared with medical treatment in symptomatic carotid disease is established, provided that the surgical procedure can be performed with a perioperative morbidity and mortality of <6%. The advantage of carotid endarterectomy for asymptomatic patients is less established. An alternative treatment, carotid artery stenting, has been developed. This treatment is used frequently in both symptomatic and asymptomatic patients. In the last decade, major advantages in medical primary prevention of cerebrovascular and cardiovascular disease have been accomplished. The control groups in the large trials for asymptomatic carotid artery disease (ACAS and ACST) originate from more than a decade ago and, for the most part, have not received a medical primary prevention strategy that would now be considered the standard according to current national and international guidelines. For this reason, a three-arm trial (SPACE2; http://www.space-2.de) with a hierarchical design and a recruitment target of 3640 patients is chosen. Firstly, a superior trial of intervention (carotid artery stenting or carotid endarterectomy) vs. state-of-the-art conservative treatment is designed. In case of superiority of the interventions, a noninferiority end-point will be tested between carotid artery stenting and carotid endarterectomy. This trial is registered at Current Controlled Trials ISRCTN 78592017. [source] Modulation of angiogenesis is effective in a model of rheumatoid arthritisJOURNAL OF ANATOMY, Issue 5 2002A. O. Afuwape A feature of rheumatoid arthritis (RA) is prominent hyperplasia of the synovium, which results in an increased distance between the invasive pannus and the existing synovial vasculature. Concomitantly the hyperplastic tissue imposes an augmented metabolic demand on the pre-existing vasculature. As a consequence the synovium in RA becomes hypoxic, resulting in an increased rate of formation of new blood vessels, to supply nutrients and oxygen. Targeting the vasculature in RA is a potential therapeutic approach in RA. VEGF, a key vascular permeability and angiogenic factor, is expressed in RA. In this study we utilised adenovirus expressing the secreted form of the extracellular domain of the Flt-1 VEGF receptor (sFlt-1) to inhibit VEGF in the collagen-induced arthritis (CIA) model, to determine whether blocking the effects of vegf might be an effective treatment for RA. AdvsFlt-1, administered intravenously on the first day of arthritis, significantly suppressed CIA. For example, on d 6 of arthritis the mean increase in paw thickness, which reflects oedema, for untreated and null adenovirus-treated animals was 0.23 ± 0.05 mm and 0.38 ± 0.08, respectively, compared to 0.07 ± 0.05 for AdvsFlt-1-treated mice (P < 0.001 vs. Adv0-treated and untreated mice by 2-way anova). Western blot analyses revealed the presence of a 100-kDa band, corresponding to human sFlt-1, in liver extracts from arthritic mice infected with AdvsFlt-1 at 24 h but not 72 h after infection. This band was absent in liver extracts from Adv0-infected mice and all synovial extracts. Measurement of protein levels by ELISA demonstrated the presence of sFlt-1 in liver, synovium and serum, although levels declined by 72 h post infection. These data suggest efficient but transient expression of sFlt-1. Sera from adenovirus infected mice were found to contain antiviral antibodies and additionally, sera from AdvsFlt-1-infected but not Adv0-infected mice recognised human recombinant sFlt-1. These observations demonstrate that adenoviral mediated delivery of human sFlt-1 leads to transient gene expression and suppression of CIA. This effect is reduced later in the course of disease due to the expression of antiadenovirus as well as antisFlt-1 antibodies. Future studies will assess the effect of combination treatment, using AdvsFlt-1 together with anti-TNF(antibody, to prolong the beneficial effects of VEGF blockade. These results suggest that blocking the pro-angiogenic and permeability action of VEGF may be beneficial for treatment of RA. [source] Saltmarsh erosion and restoration in south-east England: squeezing the evidence requires realignmentJOURNAL OF APPLIED ECOLOGY, Issue 5 2005MINEKE WOLTERS Summary 1Saltmarshes in south-east England have been eroding rapidly since 1960. Recently, Hughes & Paramor (2004) and Morris et al. (2004) have presented contrasting views on the extent to which physical and biological processes might contribute to the erosion. There are three contentious issues: (i) saltmarsh erosion is the result of coastal squeeze, where sea walls prevent a landward migration of a saltmarsh in response to sea level rise; (ii) saltmarsh erosion is linked to bioturbation and herbivory of seedlings by the ragworm Nereis diversicolor; (iii) new saltmarshes will not develop on managed realignment sites where existing sea walls have been removed because of the effects of ragworms. 2In this paper, we provide a literature review of physical and biological processes relevant to the above three issues, and discuss the relative importance of these processes at different spatial and temporal scales. 3Our synthesis shows that, at a regional scale, the combination of strong winds, high tides and increased wave height appears to be responsible for the increased rate of marsh erosion and creek dissection recorded in the 1970s. There is also some laboratory evidence that bioturbation and herbivory from populations of Nereis can lead to sediment instability and loss of pioneer plant species, such as Salicornia spp. However, the field evidence is more equivocal and has been conducted at small spatial scales. 4At a large number of different managed realignment sites there is strong evidence that even if bioturbation and herbivory by Nereis have occurred, overall the effects have been insufficient to restrict plant succession of exposed sediment. 5Synthesis and applications. There is an urgent need for long-term field studies that integrate and quantify physical and biological processes and the related feedbacks at different spatial and temporal scales. Until this is completed, terms such as coastal squeeze will remain contentious and management decisions will invite criticism. [source] Idiopathic Hyperphosphatasia and TNFRSF11B Mutations: Relationships Between Phenotype and Genotype,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2003Belinda Chong Abstract Homozygous mutations in TNFRSF11B, the gene encoding osteoprotegerin, were found in affected members from six of nine families with idiopathic hyperphosphatasia. The severity of the phenotype was related to the predicted effects of the mutations on osteoprotegerin function. Introduction: Idiopathic hyperphosphatasia (IH) is a rare high bone turnover congenital bone disease in which affected children are normal at birth but develop progressive long bone deformities, fractures, vertebral collapse, skull enlargement, and deafness. There is, however, considerable phenotypic variation from presentation in infancy with severe progressive deformity through to presentation in late childhood with minimal deformity. Two recent reports have linked idiopathic hyperphosphatasia with deletion of, or mutation in, the TNFRSF11B gene that encodes osteoprotegerin (OPG), an important paracrine modulator of RANKL-mediated bone resorption. Materials and Methods: We studied subjects with a clinical diagnosis of IH and unaffected family members from nine unrelated families. Clinical, biochemical, and radiographic data were collected, and genomic DNA examined for mutations in TNFRSF11B. The relationship between the mutations, their predicted effects on OPG function, and the phenotype were then examined. Results: Of the nine families studied, affected subjects from six were homozygous for novel mutations in TNFRSF11B. Their parents were heterozygous, consistent with autosomal recessive inheritance. Four of the six mutations occurred in the cysteine-rich ligand-binding domain and are predicted to disrupt binding of OPG to RANKL. Missense mutations in the cysteine residues, predicted to cause major disruption to the ligand-binding region, were associated with a severe phenotype (deformity developing before 18 months age and severe disability), as was a large deletion mutation. Non-cysteine missense mutations in the ligand-binding domain were associated with an intermediate phenotype (deformity recognized around the age of 5 years and an increased rate of long bone fracture). An insertion/deletion mutation at the C-terminal end of the protein was associated with the mildest phenotype. Conclusion: Mutations in TNFRSF11B account for the majority of, but not all, cases of IH, and there are distinct genotype-phenotype relationships. [source] Continuous requirement for pp60-Src and phospho-paxillin during fibronectin matrix assembly by transformed cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2007Iwona Wierzbicka-Patynowski Fibronectin (FN) matrix assembly is an integrin-mediated process that is regulated by both the extracellular environment and intracellular signaling pathways. The activity of Src-family kinases is important for initiation of FN assembly by normal fibroblasts. Here we report that in HT1080 fibrosarcoma cells, Src kinase activity is required not only for the assembly of FN matrix but also for the maintenance of FN matrix fibrils at the cell surface. Dexamethasone-induced FN fibril formation by these cells was completely blocked for at least 24 h when Src-family kinase activity was inhibited by either PP1 or SU6656. Inhibition of Src after significant matrix had already been assembled, resulted in an increased rate of loss of detergent-insoluble FN. Binding of activation-dependent integrin antibodies reveals a role for Src in maintaining integrin activity. The requirement for Src kinase activity appears to depend, in part, on phosphorylation of paxillin at tyrosine 118 (Y118). Phospho-paxillin co-localized with FN fibrils, and overexpression of GFP-paxillin but not of GFP-paxillinY118F enhanced cell-mediated assembly of FN. Our results indicate that Src maintains FN matrix at the cell surface through its effect on integrin activity and paxillin phosphorylation. J. Cell. Physiol. 210: 750,756, 2007. © 2006 Wiley-Liss, Inc. [source] Experimental susceptibility of different life-stages of the giant freshwater prawn, Macrobrachium rosenbergii (de Man), to white spot syndrome virus (WSSV)JOURNAL OF FISH DISEASES, Issue 4 2002R B Pramod Kiran Studies were conducted by injecting/feeding white spot syndrome virus (WSSV) derived from infected shrimp, Penaeus monodon (Fabricius), to different life-stages, namely post-larvae, juveniles, sub-adults and adults of Macrobrachium rosenbergii (de Man). The disease was also induced in brood stock, and the eggs and larvae derived from these animals were subsequently tested for WSSV infection. All the stages except egg used for the experiment were found WSSV positive in histopathology, cross infection bioassay and polymerase chain reaction (PCR) analysis. Experimentally infected post-larvae and juveniles showed a high percentage of mortality and an increased rate of cannibalism. The cumulative mortality in post-larvae was up to 28%; with 28,40% cannibalism resulting in a maximum loss of up to 68%. In juveniles, observed mortality and cannibalism were 10,20% and 6.7,30.0%, respectively, and the maximum loss recorded was 50%. In sub-adults, mortality ranged from 2.8 to 6.7%, cannibalism was up to 20% and the total loss was up to 26.7%. Sub-adults and adults were found to be more tolerant to the infection as evidenced by the mortality pattern. A nested (two-step) PCR resulted in a 570-bp product specific to WSSV in all stages, except the eggs. [source] Ca2+ -induced permeabilization promotes free radical release from rat brain mitochondria with partially inhibited complex IJOURNAL OF NEUROCHEMISTRY, Issue 3 2005Tatyana V. Votyakova Abstract Mitochondrial complex I dysfunction has been implicated in a number of brain pathologies, putatively owing to an increased rate of reactive oxygen species (ROS) release. However, the mechanisms regulating the ROS burden are poorly understood. In this study we investigated the effect of Ca2+ loads on ROS release from rat brain mitochondria with complex I partially inhibited by rotenone. The addition of 20 nm rotenone to brain mitochondria increased ROS release. Ca2+ (100 µm) alone had no effect on ROS release, but greatly potentiated the effects of rotenone. The effect of Ca2+ was decreased by ruthenium red. Ca2+ -challenged mitochondria lose about 88% of their glutathione and 46% of their cytochrome c under these conditions, although this depends only on Ca2+ loading and not complex I inhibition. ADP in combination with oligomycin decreased the loss of glutathione and cytochrome c and free radical generation. Cyclosporin A alone was ineffective in preventing these effects, but augmented the protection provided by ADP and oligomycin. Non-specific permeabilization of mitochondria with alamethicin also increased the ROS signal, but only when combined with partial inhibition of complex I. These results demonstrate that Ca2+ can greatly increase ROS release by brain mitochondria when complex I is impaired. [source] | ||||||||||||||||||||||||||||||||||||||||