Response rate to a single dose of vinblastine administered to dogs with treatment-naive multicentric lymphoma.

Vincristine is included in vincristine, cyclophosphamide, doxorubicin and prednisone (CHOP) chemotherapy protocols, which are the gold-standard treatment for high-grade canine lymphoma. Vincristine can result in relatively high rates of gastrointestinal toxicity, whereas vinblastine is generally well tolerated and thus may represent an under-utilized and minimally toxic alternative to vincristine. Our objective was to determine the response rate and toxicity associated with a single dose of vinblastine administered to dogs with treatment-naïve, intermediate to large-cell, multicentric lymphoma. Twenty client-owned dogs were enrolled with signed owner consent. A Simon's minimax, phase II, two-stage trial was performed to test the efficacy of vinblastine administered at 2 mg/m2 IV followed by a pilot trial of vinblastine at 2.5 mg/m2 . No dogs were administered concurrent steroids or other chemotherapy. One out of 14 dogs receiving vinblastine at 2 mg/m2 demonstrated a partial response. Three out of five dogs demonstrated a partial response to vinblastine at 2.5 mg/m2 . Gastrointestinal toxicity was infrequent and low grade for both groups. The majority of dogs (80%) in the 2.5 mg/m2 dosing group developed neutropenia 1-week post administration. Vinblastine was well tolerated but minimally efficacious at a dose of 2 mg/m2 IV in dogs with treatment-naive, multicentric lymphoma. Because of poor response rates, treatment at this dose is not recommended. A small subset of dogs administered 2.5 mg/m2 had significantly improved response rates (P = 0.04), suggesting that higher doses may have improved efficacy, although further research is indicated to confirm these preliminary findings.

Central nervous system lymphoma in 18 dogs (2001 to 2015).

OBJECTIVES: To investigate the outcome of dogs with central nervous system lymphoma. MATERIALS AND METHODS: A multi-center, retrospective, observational study was conducted by reviewing medical records of 18 cases of central nervous system lymphoma from seven institutions. RESULTS: Diagnosis of lymphoma was made through cerebrospinal fluid analysis, histopathology, flow cytometry of the cerebrospinal fluid, and cytology of cerebrospinal fluid, lymph node or spleen with correlated imaging. A total of 15 of 18 dogs received specific treatment other than prednisone. Three dogs underwent chemotherapy and radiation therapy after surgical decompression, five dogs underwent chemotherapy, two dogs underwent radiation therapy after surgical decompression, three dogs underwent chemotherapy after surgical decompression and two dogs underwent radiation therapy and chemotherapy. Only one dog received prednisone, and two dogs did not receive any treatment. Overall, the median survival time was 171 days (range 1 to 1942 days). CLINICAL SIGNIFICANCE: Dogs receiving any type of treatment for central nervous system lymphoma lived longer than cases described in previous historical reports. Further studies are needed to elucidate the importance of specific treatment modalities.

Metal and nutrient dynamics on an aged intensive green roof.

Runoff and rainfall quality was compared between an aged intensive green roof and an adjacent conventional roof surface. Nutrient concentrations in the runoff were generally below Environmental Quality Standard (EQS) values and the green roof exhibited NO3(-) retention. Cu, Pb and Zn concentrations were in excess of EQS values for the protection of surface water. Green roof runoff was also significantly higher in Fe and Pb than on the bare roof and in rainfall. Input-output fluxes revealed the green roof to be a potential source of Pb. High concentrations of Pb within the green roof soil and bare roof dusts provide a potential source of Pb in runoff. The origin of the Pb is likely from historic urban atmospheric deposition. Aged green roofs may therefore act as a source of legacy metal pollution. This needs to be considered when constructing green roofs with the aim of improving pollution remediation.

Rainwater runoff retention on an aged intensive green roof.

Urban areas are characterised by large proportions of impervious surfaces which increases rainwater runoff and the potential for surface water flooding. Increased precipitation is predicted under current climate change projections, which will put further pressure on urban populations and infrastructure. Roof greening can be used within flood mitigation schemes to restore the urban hydrological balance of cities. Intensive green roofs, with their deeper substrates and higher plant biomass, are able to retain greater quantities of runoff, and there is a need for more studies on this less common type of green roof which also investigate the effect of factors such as age and vegetation composition. Runoff quantities from an aged intensive green roof in Manchester, UK, were analysed for 69 rainfall events, and compared to those on an adjacent paved roof. Average retention was 65.7% on the green roof and 33.6% on the bare roof. A comprehensive soil classification revealed the substrate, a mineral soil, to be in good general condition and also high in organic matter content which can increase the water holding capacity of soils. Large variation in the retention data made the use of predictive regression models unfeasible. This variation arose from complex interactions between Antecedant Dry Weather Period (ADWP), season, monthly weather trends, and rainfall duration, quantity and peak intensity. However, significantly lower retention was seen for high rainfall events, and in autumn, which had above average rainfall. The study period only covers one unusually wet year, so a longer study may uncover relationships to factors which can be applied to intensive roofs elsewhere. Annual rainfall retention for Manchester city centre could be increased by 2.3% by a 10% increase in intensive green roof construction. The results of this study will be of particular interest to practitioners implementing greenspace adaptation in temperate and cool maritime climates.

Magnetic Meckel's: an unusual case report of foreign body ingestion.

Foreign body ingestion in children is common. Most items pass spontaneously, however rarer cases may result in obstruction and or perforation. Ingestion of multiple magnetic items can be more troublesome, as a consequence of the ability of the items to attract across different sections of bowel, or by coalescing to form a larger foreign body. Very few cases of foreign body ingestion have led to the presentation of a complicated Meckel's diverticulum. We present of a case of an adolescent boy with intestinal obstruction secondary to multiple magnetic foreign body ingestion and sequestration within a Meckel's diverticulum.

Modelling air pollution for epidemiologic research--part II: predicting temporal variation through land use regression.

Over recent years land use regression (LUR) has become a frequently used method in air pollution exposure studies, as it can model intra-urban variation in pollutant concentrations at a fine spatial scale. However, very few studies have used the LUR methodology to also model the temporal variation in air pollution exposure. The aim of this study is to estimate annual mean NO(2) and PM(10) concentrations from 1996 to 2008 for Greater Manchester using land use regression models. The results from these models will be used in the Manchester Asthma and Allergy Study (MAAS) birth cohort to determine health effects of air pollution exposure. The Greater Manchester LUR model for 2005 was recalibrated using interpolated and adjusted NO(2) and PM(10) concentrations as dependent variables for 1996-2008. In addition, temporally resolved variables were available for traffic intensity and PM(10) emissions. To validate the resulting LUR models, they were applied to the locations of automatic monitoring stations and the estimated concentrations were compared against measured concentrations. The 2005 LUR models were successfully recalibrated, providing individual models for each year from 1996 to 2008. When applied to the monitoring stations the mean prediction error (MPE) for NO(2) concentrations for all stations and years was -0.8µg/m³ and the root mean squared error (RMSE) was 6.7µg/m³. For PM(10) concentrations the MPE was 0.8µg/m³ and the RMSE was 3.4µg/m³. These results indicate that it is possible to model temporal variation in air pollution through LUR with relatively small prediction errors. It is likely that most previous LUR studies did not include temporal variation, because they were based on short term monitoring campaigns and did not have historic pollution data. The advantage of this study is that it uses data from an air dispersion model, which provided concentrations for 2005 and 2010, and therefore allowed extrapolation over a longer time period.

Modelling air pollution for epidemiologic research--Part I: A novel approach combining land use regression and air dispersion.

A common limitation of epidemiological studies on health effects of air pollution is the quality of exposure data available for study participants. Exposure data derived from urban monitoring networks is usually not adequately representative of the spatial variation of pollutants, while personal monitoring campaigns are often not feasible, due to time and cost restrictions. Therefore, many studies now rely on empirical modelling techniques, such as land use regression (LUR), to estimate pollution exposure. However, LUR still requires a quantity of specifically measured data to develop a model, which is usually derived from a dedicated monitoring campaign. A dedicated air dispersion modelling exercise is also possible but is similarly resource and data intensive. This study adopted a novel approach to LUR, which utilised existing data from an air dispersion model rather than monitored data. There are several advantages to such an approach such as a larger number of sites to develop the LUR model compared to monitored data. Furthermore, through this approach the LUR model can be adapted to predict temporal variation as well as spatial variation. The aim of this study was to develop two LUR models for an epidemiologic study based in Greater Manchester by using modelled NO(2) and PM(10) concentrations as dependent variables, and traffic intensity, emissions, land use and physical geography as potential predictor variables. The LUR models were validated through a set aside "validation" dataset and data from monitoring stations. The final models for PM(10) and NO(2) comprised nine and eight predictor variables respectively and had determination coefficients (R²) of 0.71 (PM(10): Adj. R²=0.70, F=54.89, p<0.001, NO(2): Adj. R²=0.70, F=62.04, p<0.001). Validation of the models using the validation data and measured data showed that the R² decreases compared to the final models, except for NO(2) validation in the measured data (validation data: PM(10): R²=0.33, NO(2): R²=0.62; measured data: PM(10): R²=0.56, NO(2): R²=0.86). The validation further showed low mean prediction errors and root mean squared errors for both models.

Mammary gland differentiation by early life exposure to enantiomers of the soy isoflavone metabolite equol.

The role of soy in reducing breast cancer risk has been suggested to be associated with early exposure to isoflavones, which alter mammary gland morphology. The objective of the study was to determine the effect of dietary exposure to the enantiomers of a key soy isoflavone metabolite, equol, on mammary gland development and later chemoprotection using the DMBA-induced animal model of breast cancer. Animals were exposed to S-(-)equol or R-(+)equol (250 mg/kg diet) during the neonatal (0-21 days) or prepubertal (21-35 days) periods only. Histological evaluation of the mammary glands showed that both enantiomers fed neonatally via the dam led to significant precocial mammary gland differentiation. By day 50, early S-(-)equol or R-(+)equol exposure resulted in a decrease in immature terminal end structures and an increase in mature lobules, suggesting an early 'imprinting' effect. Despite these morphological changes to the mammary gland, neonatal and prepubertal exposure to equol had no long-term chemoprevention against mammary tumors induced by DMBA, although for R-(+)equol there was a trend to delaying tumor formation. In summary, early exposure to equol was not chemopreventive, but neither did it increase tumor formation in response to DMBA, suggesting exposure in early life does not influence breast cancer risk.

Serotonin transporter polymorphism, memory and hippocampal volume in the elderly: association and interaction with cortisol.

The s allele variant of the serotonin transporter gene (5-HTT) has recently been observed to moderate the relationship of stress to depression and anxiety. To date no study has considered interactive effects of 5-HTT genotype, stress and hypothalamic-pituitary-adrenal (HPA) function on cognition in healthy, older adults, which may reflect developmental, functional or neurodegenerative effects of the serotonin transporter polymorphism. We investigated whether 5-HTT genotype interacts with cumulative life stress and HPA-axis measures of waking and diurnal cortisol slope to impact cognition in 154 non-depressed, older adults. Structural images of hippocampal volume were acquired on a subsample of 56 participants. The 5-HTT s allele was associated with both significantly lower delayed recall and higher waking cortisol levels. Presence of the s allele interacted with higher waking cortisol to negatively impact memory. We also observed a significant interaction of higher waking cortisol and the s allele on lower hippocampal volume. Smaller hippocampi and higher cortisol were associated with lower delayed recall only in s allele carriers. No impact or interactions of cumulative life stress with 5-HTT or cortisol were observed. This is the first investigation to identify an association of the 5-HTT s allele with poorer memory function in older adults. The interactive effects of the s allele and waking cortisol levels on reduced hippocampal volume and lower memory suggest that the negative effect of the serotonin polymorphism on memory is mediated by the HPA axis. Further, given the significant association of the s allele with higher waking cortisol in our investigation, future studies may be needed to evaluate the impact of the serotonin transporter polymorphism on any neuropsychiatric or behavioral outcome which is influenced by HPA axis function in older adults.

Hidden process models for animal population dynamics.

Hidden process models are a conceptually useful and practical way to simultaneously account for process variation in animal population dynamics and measurement errors in observations and estimates made on the population. Process variation, which can be both demographic and environmental, is modeled by linking a series of stochastic and deterministic subprocesses that characterize processes such as birth, survival, maturation, and movement. Observations of the population can be modeled as functions of true abundance with realistic probability distributions to describe observation or estimation error. Computer-intensive procedures, such as sequential Monte Carlo methods or Markov chain Monte Carlo, condition on the observed data to yield estimates of both the underlying true population abundances and the unknown population dynamics parameters. Formulation and fitting of a hidden process model are demonstrated for Sacramento River winter-run chinook salmon (Oncorhynchus tshawytsha).

What lies beneath?--issues in the representation of air quality management data for public consumption.

Policy developments in the UK and the European Union (EU) now require local authorities to engage the general public within the whole process of local air quality management (AQM). Indeed, this is considered to be one of the means by which air quality issues can gain public support and help ensure future improvements. One of the outcomes of this is that data sets associated with air quality management must now be disseminated to nonscientific audiences. This is a problematic task for a number of reasons. One of these relates to the fact that air quality data are complex and variable, yet the public demand representations that are clear and unambiguous. Another important issue is associated with the increasing use of geographical information systems (GIS) and mapping tools, which allow data to be generated and summarised in many different ways without due regard to the effects that the choice of methodology can have on the way data are interpreted. The variation in information obtained using different techniques can represent a problem, but is also an opportunity to further explore data sets and to draw out specific information for complementary air quality management tasks. However, at present, the lack of a well-grounded methodology and guidance for handling and representing the spatial aspects of data sets means that consistency between areas and authorities is not maintained. Such a situation fosters ambiguity at several levels, from the individual's perception of public health-related information to an Authority's rationale for the selection of air quality management areas (AQMAs). This paper investigates a number of issues relating to spatial data generation and representation in the field of air quality management, particularly in relation to emissions inventory data. The examples are UK based, but the issues raised are applicable to other examples and areas. One case study examines the difference in information gained through a number of common mapping techniques and shows how different 'problems' can be identified merely as an artefact of the dissemination technique itself. To further illustrate the difficulties and conflicts faced in representing and explaining these data in a practical context, reference is then also made to the methods recently considered by an example London authority. The paper concludes with a call for the development of a more standardised method for representing different types of air quality management-related data, which may help to overcome these problems in the future.

Uveal effusion after cataract surgery: an echographic study.

PURPOSE: To determine the incidence of uveal effusion after cataract surgery and to relate its presence to selected preoperative, intraoperative, and postoperative variables. DESIGN: Prospective consecutive observational case series. PARTICIPANTS: Two hundred seven eyes of 205 subjects undergoing cataract surgery. METHODS: Several preoperative, intraoperative, and postoperative variables of potential significance in uveal effusion after cataract surgery were studied. On the first postoperative day and within 2 weeks after the surgery, subjects were examined clinically and echographically with B-scan for evidence of suprachoroidal (uveal) effusion. When effusion was present, follow-up examinations were performed until complete resolution was documented. MAIN OUTCOME MEASURES: Echographic presence of uveal effusion in the postoperative period. RESULTS: Uveal effusion was documented echographically in 12 patients (5.8%). Only one of these cases was clinically evident. All effusions were small and resolved with no intervention. The presence of postoperative hypotony related to wound leak (intraocular pressure <10 mmHg) was significantly correlated with uveal effusion after cataract surgery (P<0.0001). The combination of oral acetazolamide and topical pilocarpine gel given after the surgery also correlated with effusion (P<0.02). Intraoperative complications and prolonged phacoemulsification time were not shown to be risk factors for effusion. CONCLUSIONS: Uveal effusion is rarely seen after modern, small-incision, closed-system cataract surgery. It is correlated with postoperative hypotony related to wound leak and with the administration of both oral acetazolamide and topical pilocarpine after surgery.

Psychotic symptoms in posttraumatic stress disorder.

Recent data suggest that the presence of psychotic symptoms in patients suffering from posttraumatic stress disorder (PTSD) may represent an underrecognized and unique subtype of PTSD. Among combat veterans with PTSD, 30% to 40% report auditory or visual hallucinations and/or delusions. The presence of psychotic symptoms in PTSD is associated with a more severe level of psychopathology, similar to that of chronic schizophrenia. In this review, the differential diagnosis of psychotic symptoms in PTSD is discussed, including possible comorbid schizophrenia, psychotic depression, substance-induced psychosis, and personality disorder. A recent biologic study supporting the existence of a unique subtype of PTSD with psychotic features is also addressed, as are the similarities between PTSD with psychotic features and psychotic depression disorder. Finally, data on the treatment implications of psychotic symptoms in PTSD are presented. The intriguing recent findings on psychotic symptoms in PTSD need further investigation in noncombat-related PTSD populations before findings can be generalized to all individuals with PTSD.

Orbital infarction and melting in a patient with systemic lupus erythematosus.

OBJECTIVE: To present a patient with systemic lupus erythematosus who developed infarction and melting of the orbit secondary to her systemic disease. DESIGN: A case report. PARTICIPANT: A 61-year-old white woman with a 5-year history of systemic lupus erythematosus. METHODS: The patient presented with left orbital pain, limitation of extraocular movements, and a fistula from the ethmoid sinus to the upper eyelid. A detailed examination with computerized tomography, ultrasound, and a comprehensive medical evaluation with laboratory testing was performed. Histopathologic analysis with special stains of the orbital tissues was also performed. RESULTS: Histopathologic examination of the biopsy specimens revealed the features of an inflammatory process involving the orbit, similar to a panniculitis. These include a lymphocytic reaction with a predominance of plasma cells, vasculitis with occlusion, and thickening of the vessel walls, necrosis, and hyalinization of fat. CONCLUSION: This is a unique case in which infarction and melting of the entire orbital structures occurred in the presence of systemic lupus erythematosus. The underlying disease process is a lupus-related panniculitis. The authors stress that this is a very rare entity and that other diseases should be ruled out before entertaining this diagnosis.

Glucocorticoid effects on mesotelencephalic dopamine neurotransmission.

Multiple neurochemical estimates were used to examine peripheral corticosterone (CORT) effects in dopaminergic terminal regions. Acute CORT administration, which elevated plasma CORT (5 h), slightly decreased dihydroxyphenylacetic acid (DOPAC) to dopamine (DA) ratios in the striatum but not in other regions examined. Two weeks of adrenalectomy (ADX) increased both medial prefrontal cortex DOPAC/DA and homovanillic acid (HVA)/DA and striatal HVA/DA. A reciprocal pattern of changes was observed with CORT replacement in ADX animals. In contrast, CORT replacement in ADX animals did not significantly influence tyrosine hydroxylase content, basal dihydroxyphenylalanine (DOPA) accumulation after NSD 1015 treatment or the decline in DA after alpha-methyl-para-tyrosine, suggesting that neither DA neuronal activity nor release are altered by CORT. Moreover, neither gamma-hydroxybutyric acid lactone-induced increases in DOPA accumulation or stress-induced increases in DA utilization were influenced by CORT replacement, indicating that neither autoreceptor regulation of DA synthesis nor acute stress regulation of DA utilization are changed by CORT. The findings are most consistent with direct inhibition of basal DA metabolism in the medial prefrontal cortex and striatum. The possible physiological and behavioral significance of this inhibition is being further explored.

Strain differences in mesotelencephalic dopaminergic neuronal regulation between Fischer 344 and Lewis rats.

Differences in the behavioral responses of Lewis and Fischer (F344) inbred rat strains to stress and psychoactive drugs have been related to differences in the expression of various regulatory proteins in regions containing mesolimbic dopamine (DA) neurons. The present study compared basal and stimulated neurochemical estimates of DA utilization and synthesis in mesocortical, mesolimbic and nigrostriatal DA terminal regions of these two strains. In unstressed control animals, the Lewis strain had lower DA concentrations in the dorsal striatum (ST; 80.3% of F344) and lower basal dihydroxyphenylalanine (DOPA) accumulation after m-hydroxybenzylhydrazine (NSD 1015) treatment in the medial prefrontal cortex (mPfx; 75.3% of F344). Similar differences were observed in vehicle-injected animals. No strain differences in basal neurochemistry were apparent in the nucleus accumbens shell (NAs) or core (NAc). In response to restraint stress, dihydroxyphenylacetic acid (DOPAC) to DA ratios in the mPfx, NAs and ST increased in the F344 but not the Lewis strain. However, restraint stress did not significantly increase DOPA accumulation in the F344 strain. This latter finding was not due to a deficit in synthesis capacity, as gamma-hydroxybutyric acid lactone (GBL) increased DOPA accumulation significantly more in F344 than Lewis animals. Finally, haloperidol increased DA utilization similarly in the two strains. Together these findings suggest that the inbred, behaviorally divergent F344 and Lewis rats have selective differences in mesocortical, nigrostriatal and mesolimbic DA neuronal regulation.

A study of the aetiology of pseudopregnancy in the bitch and the effect of cabergoline therapy.

Thirty-two permanently pseudopregnant bitches were treated with the anti-prolactin drug cabergoline. They had all been ovariohysterectomised up to five months after their last season, in some cases over two years previously, when most were reported as showing no signs of the condition. The clinical signs were mainly behavioural, the majority being aggressive, and a small number were lactating. The efficiency of the cabergoline therapy was classified by the owners as 'excellent' or 'good' in 50 per cent of the cases, and fair in 36 per cent. The rate of success was markedly better than in similar cases treated with reproductive steroids. In all but one of the bitches, the plasma prolactin concentrations were basal.

Separation induced changes in squirrel monkey hypothalamic-pituitary-adrenal physiology resemble aspects of hypercortisolism in humans.

When separated from groups, squirrel monkeys respond with significant increases in plasma cortisol and adrenocorticotropic hormone (ACTH). While cortisol remains elevated above pre-separation levels, significant reductions occur in ACTH. Monkeys that respond with greater increases in cortisol subsequently exhibit greater reductions in ACTH, which suggests that reductions in ACTH are mediated by corticosteroid feedback. Monkeys that respond with greater increases in cortisol also tend to exhibit greater cerebrospinal fluid levels of the dopamine metabolite HVA, but not the norepinephrine metabolite MHPG, or corticotropin-releasing factor (CRF). Attenuation of corticosteroid feedback with metyrapone results in significant increases in circulating ACTH, and in older monkeys increases plasma HVA. Similar findings in humans have been reported in clinical studies of hypercortisolism and major depression.