The MS-MS Determination of the Fragmentation Pathways of Some Substituted 1,2,3-Benzotriazin-4-ones with Possible Applications in Metabolic Studies

1,2,3-Benzotriazin-4-one derivatives are extensively used as herbicides, insecticides and nematicides. Incorporation of these compounds into the human food chain is a cause for concern, since their toxicity to man is well documented. This work describes the development of a data-base of classical 1,2,3-benzotriazin-4-one fragmentation patterns and consequent sequential neutral mass losses which allows the prediction of the presence of a triazinone derived compound. Positive and negative ion tandem mass spectrometry techniques were employed since they allow rapid and sensitive structural characterization of drugs and their metabolites in biological fluids through the unambiguous monitoring of daughter ions from pre-selected primary ions.     

Interferon Alfa-2b or Not 2b? Significant Differences Exist in the Decision-Making Process between Melanoma Patients Who Accept or Decline High-Dose Adjuvant Interferon Alfa-2b Treatment

BACKGROUND: Patients with thick (Breslow>4 mm) primary melanoma and/or regional nodal metastasis have a high risk of tumor recurrence. High-dose adjuvant interferon (IFN) alfa-2b offers/=50% risk of recurrence/disease-related mortality and offered IFN. Telephone surveys delineated reasons behind patients' decisions to accept IFN. RESULTS: Acceptors, 60 of 135 (45%), decided to take IFN alfa-2b whereas 75 of 135 (55%) declined. Being female (OR, 2.4; 95% CI, 1.17-5.03; p=.017) and positive SLN status (OR, 2.2; 95% CI, 1.01-4.97; p=.048) were strongly associated with patients who chose IFN. Acceptors of IFN were younger, more influenced by physicians, and less affected by depression and side effect profile (p<.05 for all). Decliners were more concerned by strained relationships with family and social life (p<.05). CONCLUSIONS: Gender and positive SLN were predictive of high-risk melanoma patients' acceptance of IFN treatment. Physician insight into melanoma patients' therapeutic decision-making process can guide patients through this difficult disease.     

Absence of effects of prolonged simvastatin therapy on nocturnal sleep in a large randomized placebo-controlled study

1It has been suggested that lipophilic HMG CoA reductase inhibitors, like lovastatin and simvastatin, may cause sleep disturbance. 2Six hundred and twenty-one patients at increased risk of coronary heart disease were randomized in a single centre to receive 40 mg daily simvastatin, 20 mg daily simvastatin or matching placebo. To assess the effects of prolonged use of simvastatin on nocturnal sleep quality and duration, a sleep questionnaire was administered to 567 patients (95% of 595 survivors) at an average of 88 weeks (range: 44–129 weeks) after randomization. 3The main outcome measures were sleep-related problems and use of sleep-enhancing medications reported during routine study follow-up visits, and responses to the sleep questionnaire about changes in sleep duration and about various sleep events during the preceding month. 4No differences were observed between the treatment groups in the frequency of sleep-related problems reported, in the proportion of follow-up visits at which such problems were reported, or in the use of sleep-enhancing medications. The numbers who stopped study treatment were similar in the different treatment groups, and no patient stopped principally because of insomnia. In response to the sleep questionnaire, there were no significant differences between the treatment groups in reports of various sleep events during the preceding month, except that slightly fewer patients allocated simvastatin reported waking often. No differences in sleep duration were observed. 5This placebo-controlled trial does not indicate any adverse effects of prolonged treatment with simvastatin on systematically sought measures of sleep disturbance.     

Hyperglycaemia and mortality from acute stroke

Hyperglycaemia has been observed after acute stroke, and isassociated with a poor prognosis. It is not known whether thisis due to the stress response of the acute illness or whetherhyperglycaemia is, in itself, harmful to ischaemic nervous tissue.Seventy-one patients admitted to hospital with acute strokeand no history of diabetes or other acute illness were recruited,and fasting blood sampling was carried out within 24 h of symptomonset, for plasma glucose and stress hormones and levels ofhaemoglobin A1c (HbA1c). Computerized tomography of the brainwas carried out on 77% of the subjects. The subjects were followedup for 3 months or until death. Glucose levels were higher insubjects who died during the course of the study (p=0.025),but this relationship became non-significant after age (p<0.001) and cortisol (p= 0.001) levels were taken into accountwith multivariate analysis. The correlation between serum cortisoland the volume of the lesion on CT scan was also stronger thanthe relation of glucose with volume. Haemoglobin A1c had norelationship with either mortality or lesion volume. These findingssuggest that the hyperglycaemia seen after an acute stroke issecondary to a stress response and they do not support the theoryof hyperglycaemia being harmful to ischaemic nervous tissue.These findings have implications for the treatment of acutestroke with hypoglycaemic agents.     

A Predominantly Adrenaline-secreting Phaeochromocytoma

A 61-year-old woman who presented with diabetes, nausea, weightloss and sweating was found to have a phaeochromocytoma secretingadrenaline, with a small amount of N-methyIadrenaline. Therewas no significant increase in noradrenaline secretion. Shewas normotensive, and developed profound hypotension in responseto the -adrenergic antagonist phenoxybenzamine. These featuresare unusual in phaeochromocytoma, but similar features occurredin the very few previous reported cases of pure adrenaline-secretingphaeochromocytoma. We conclude that it is important to identifysuch patients, so that they should not be given -adrenergicantagonist drugs.     

The natural history and clinical consequences of aspiration in acute stroke

Sixty consecutive patients admitted to a teaching hospital withacute stroke were studied prospectively for 3 months to definethe natural history and consequences of lung aspiration. Usingvideofluoroscopy, aspiration was identified in 25 patients (42%)within 72 h of stroke onset, and had resolved in all but threepatients (8%) after 3 months. It was closely related to thepresence of dysphagia, which itself resolved within 2 weeksin all but the persistent aspirators. Lower respiratory tractinfection (LRTI) was more common in aspirating patients (68%)than non-aspirators (6%). The use of intravenous fluids withoutoral intake did not appear to prevent LRTI in aspirating patientswho were also dysphagic. Pneumonia occurred after 2 weeks inthe three patients subsequently found to aspirate persistently.Aspiration is a transient phenomenon in most cases of acutestroke; it is associated with a high incidence of LRTI, butmortality in this series was not significantly associated eitherwith respiratory tract infection or aspiration itself.     

Coeliac disease,epilepsy, and cerebral calcifications: association with TG6 autoantibodies

A 4‐year‐old boy presented with occipital seizures but normal initial neuroimaging and proved refractory to antiepileptic medications. On repeat neuroimaging after 1 year, he had developed bi‐occipital calcification and was then found to have positive coeliac serology. He was diagnosed with coeliac disease, epilepsy, and cerebral calcifications (CEC) and became seizure free after starting the gluten‐free diet. Positive antibody binding to neurons and glia was demonstrated on indirect immunofluorescence. High levels of immunoglobulin‐A directed against transglutaminase isoenzyme 6 (TG6) were found in the patient’s serum. The positive response to the diet, TG6 antibodies, and neuronal antibody binding suggest that CEC might be autoimmune in nature, as in other extra‐intestinal manifestations of gluten‐related diseases, such as gluten ataxia.