Ozonation of Gabapentin in Water─Investigating Reaction Kinetics and Transformation Mechanisms of a Primary Amine Using Isotopically Labeled Ozone.

Aliphatic amines are abundant micropollutants in wastewater treatment plant effluents. In order to mitigate such micropollutants, ozonation is one of the most commonly employed advanced treatment processes. Current research regarding ozone efficiency is heavily focusing on reaction mechanisms of different contaminant groups, including structures with amine moieties as reactive sites. This study analyzes pH-dependent reaction kinetics and pathways of gabapentin (GBP), an aliphatic primary amine with an additional carboxylic acid group. The transformation pathway was elucidated applying a novel approach using isotopically labeled ozone (18O) and quantum chemistry calculations. While the direct reaction of GBP with ozone is highly pH-dependent and slow at pH 7 (13.7 M-1 s-1), the rate constant of the deprotonated species (1.76 × 105 M-1 s-1) is comparable to those of other amine compounds. Pathway analysis based on LC-MS/MS measurements revealed that ozonation of GBP leads to the formation of a carboxylic acid group and simultaneous nitrate formation, which was also observed in the case of the aliphatic amino acid glycine. Nitrate was formed with a yield of approximately 100%. Experiments with 18O-labeled ozone demonstrated that the intermediate aldehyde does most likely not include any oxygen originating from ozone. Furthermore, quantum chemistry calculations did not provide an explanation for the C-N scission during GBP ozonation without ozone involvement, although this reaction was slightly more favorable than for respective glycine and ethylamine reactions. Overall, this study contributes to a deeper understanding of reaction mechanisms of aliphatic primary amines during wastewater ozonation.

Hydrocephalus in a yellow-headed Amazon parrot (Amazona ochrocephala oratrix).

A 37-year-old female yellow-headed Amazon parrot (Amazona ochrocephala oratrix) was presented after a 4-month-period behavior change and intermittent episodes of obtunded mentation. Clinical findings on physical examination included ataxia, a weak grasp, and reluctance to move. Results of magnetic resonance imaging were consistent with severe hydrocephalus without evidence of cerebrospinal fluid obstruction. The bird was treated with tapering dosages of prednisolone over a 4-month period, during which time the episodes did not occur. Discontinuation of treatment was attempted several times but resulted in relapse. After 3.5 years of maintenance treatment with prednisolone, the bird was presented subsequent to a 5-hour episode of obtunded mentation and worsening neurologic signs. Despite increasing the dose of prednisolone and providing additional supportive care, the bird's condition worsened, and euthanasia was elected. Necropsy findings included severe hydrocephalus with significant loss of right cerebral parenchyma and no evidence of cerebrospinal fluid obstruction. Histologic examination of the remaining cerebral parenchyma revealed a moderate, multifocal, cellular infiltrate; encephalomalacia; fibrosis; and hemosiderosis in tissue adjacent to the distended ventricles. Other findings included hepatic vacuolar degeneration. Diagnostic imaging and postmortem findings were consistent with a diagnosis of hydrocephalus ex vacuo. To our knowledge, this is the first report of hydrocephalus in an Amazon parrot as well as the first report of hydrocephalus in any avian species associated with long-term follow-up and prolonged corticosteroid treatment.

Neoplastic pleocytosis in a dog with metastatic mammary carcinoma and meningeal carcinomatosis.

A 12-year-old female spayed Labrador Retriever was presented with a history of seizures and abnormal vocalization. Approximately 1 year before presentation, multiple mammary cysts had been surgically excised. A mammary mass was noted on physical examination, and 2 separate parenchymal brain lesions were found on imaging studies. Cerebrospinal fluid (CSF) collected from the cisterna magna was analyzed, and abnormalities included moderate pleocytosis with atypical discrete round cells that occasionally formed loose clusters. The dog was euthanized, and on necropsy a primary solid mammary carcinoma was identified as well as multiple metastatic foci in the brain with diffuse meningeal involvement. The cells in the CSF had a morphologic appearance similar to the cells in the primary mammary tumor and in the metastatic tumors in the brain. On immunostaining, cells from the primary mammary tumor, the brain tumors, and the CSF expressed cytokeratin. The CSF cells did not express CD18, CD3, or CD79a. A final diagnosis of mammary carcinoma with brain metastasis and meningeal carcinomatosis was made.

Outpatient cardiac rehabilitation attendance in England: variability by region and clinical characteristics.

PURPOSE: Cardiac rehabilitation is an effective but underprovided treatment for patients recovering from acute cardiac events. The geographical spread of provision has not been investigated recently in any country. This study aimed to investigate the level of participation in cardiac rehabilitation programs of patients following myocardial infarction or revascularization (eligible patients) and the geographical equity of attendance. METHODS: Questionnaire data were collected from all cardiac rehabilitation centers in England for the year 2003/2004. The number of patients attending rehabilitation was compared with eligible patients across the 9 Government Office Regions of England as indicated by Hospital Episode Statistics. RESULTS: Nationally, 29% of eligible patients attended rehabilitation, while within various regions, the proportion of eligible patients participating in rehabilitation ranged between 14% (95% CI, 13.2-14.3) and 37% (95% CI, 36.6-37.6). Participation also differed significantly by primary cardiac event: myocardial infarction, 25%; percutaneous coronary intervention, 24%; and coronary artery bypass surgery, 66% (P < .001). CONCLUSION: The participation rate of eligible patients in cardiac rehabilitation was low in all regions. There were large differences between regions with widely varying incidence of attendance in different parts of the country.

Economic burden of cardiovascular diseases in the enlarged European Union.

AIMS: Cardiovascular disease (CVD), together with its main components, coronary heart disease (CHD), and cerebrovascular diseases, is the main source of morbidity and mortality in the European Union (EU), but to date, there has not been any systematic cost-of-illness study to assess the economic impact of CVD in the EU. METHODS AND RESULTS: CVD-related expenditure was estimated using aggregate data on morbidity, mortality, and healthcare resource use. Healthcare costs were estimated from expenditure on primary, outpatient, emergency, and inpatient care, as well as medications. Costs of unpaid care and lost earnings due to morbidity and premature death were included in the study. CVD was estimated to cost the EU Euro 169 billion annually, with healthcare accounting for 62% of costs. Productivity losses and informal care represented 21% and 17% of costs, respectively. CHD represented 27% and cerebrovascular diseases 20% of overall CVD costs. CONCLUSION: CVD is a leading public health problem. Our study is the first to assess the economic burden of CVD across the EU, and our results should help policy makers evaluate policy impact and prioritize research expenditures. However, because of data unavailability, our study has important limitations, which highlight the need for more accurate and comparable CVD-specific information.

Eating disorders and emotional and physical well-being: associations between student self-reports of eating disorders and quality of life as measured by the SF-36.

OBJECTIVE: To assess health-related quality of life (HRQoL) in subjects with eating disorders in terms of eating disorder type and in relation to self-reports of longstanding illness, depression and self-harming behaviours. METHOD: Data on eating disorder history, SF-36 health status, longstanding illness, and self-reported frequencies of depression, self-harming behaviour, and suicidal thoughts or acts were collected during 1996 as part of a UK postal survey of students' health. Completed questionnaires were returned by 1439 of 3750 students (response rate 42%). RESULTS: Eighty-three respondents (5.8%; 8.9% of females) reported a probable eating disorder history: 54 (3.8%) bulimia nervosa, 22 (1.6%) binge eating disorder, and 7 (0.5%) anorexia nervosa. Eating disorder subjects reported more impairment in SF-36 emotional than physical well-being, with significantly lower mental (p < 0.001) but not physical (p = 0.21) component summary scores. This was most evident in bulimia nervosa and binge eating disorder subjects. Anorexia nervosa subjects reported fewer SF-36 emotional limitations although they were significantly more likely to report depression, self-harming behaviour, and suicidal ideation. DISCUSSION: An eating disorder history is accompanied by HRQoL impairment primarily in emotional well-being. Anorexia nervosa subjects perceive fewer limitations than subjects with other eating disorders. While this is consistent with previous reports of better SF-36 emotional well-being in those with restrictive eating behaviours, it may also suggest that the SF-36 is insensitive to emotional distress in anorexia nervosa.

Health status of people using complementary and alternative medical practitioner services in 4 English counties.

OBJECTIVES: This study was undertaken to establish the health status of users of complementary and alternative medicine (CAM) services in England. METHODS: A postal questionnaire (response rate: 64%) covering long-standing illness, use of conventional medical and CAM services, and the United Kingdom Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was sent to more than 14 000 adults in 4 counties. RESULTS: Sixty percent of CAM users reported having a chronic illness or disability; back pain and bowel problems were the conditions most commonly reported. Regardless of whether chronic illness was reported, CAM users reported poorer health than nonusers, particularly in the dimensions of pain and physical disability, and made more visits to general practitioners. CONCLUSIONS: In England, users of CAM services have poorer physical health than nonusers and make more frequent use of conventional medical services.