Development and validation of an automated static headspace gas chromatography-mass spectrometry (SHS-GC-MS) method for monitoring the formation of ethyl methane sulfonate from ethanol and methane sulfonic acid

An automated sample preparation and analysis procedure was developed to monitor the formation of ethyl methane sulfonate from reaction mixtures containing ethanol and methane sulfonic acid. The system is based on a liquid handling robot combined with a static headspace module. The formed ethyl methane sulfonate is analysed after derivatisation with pentafluorothiophenol using static headspace-gas chromatography–mass spectrometry (SHS-GC–MS).Using the automated reaction–derivatisation–headspace GC–MS system, the formation of ethyl methane sulfonate can be monitored in different reaction mixtures under different reaction conditions, including temperature, water content and pH. Excellent linearity, repeatability and robustness were obtained, allowing the system to be used in kinetic studies.     

Validity of the BPRS, the BDI and the BAI in dual diagnosis patients

AIM: The psychometric properties of the Brief Psychiatric Rating Scale, the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI) were tested in a sample of 134 patients with a substance use disorder and a non-substance related psychiatric disorder in a special inpatient dual diagnosis treatment unit. METHODS: Subjects were assessed at baseline. At discharge on average 6 months post-intake, 78% of patients were re-assessed using the same instruments. All instruments were tested in (1) their ability to discriminate patients with different diagnoses at baseline and follow-up using comparison of area under the curves, and (2) their temporal stability. Moderator regression was used to test whether thought disorder at baseline had any effect on the test-retest rank-order stability of other instruments. FINDINGS: The BPRS Thought Disorder scale was able to discriminate between patients with and without schizophrenia spectrum diagnoses, and the BDI was able to discriminate between patients with and without mood disorders and schizoaffective disorders at intake to treatment, and each instrument was significantly better than the other at discriminating relevant diagnostic groups. Discriminant correlations between the BDI and the BAI were high and statistically significant. Moderator regression analyses showed no indication that any of the scales were less stable at higher levels of thought disorder. CONCLUSIONS: It is concluded that dual diagnosis patients can be reliably assessed for symptoms using the BDI and some subscales of the BPRS.     

Increased intraocular pressure and hypothermia following injection of calcium into the rabbit third ventricle

Calcium administration into the third ventricle of rabbits resulted in a dose-dependent elevation of intraocular pressure (IOP) and reduction in deep body temperature. These responses were not inhibited by pretreatment with atropine, phentolamine, propanolol or indomethacin. Pretreatment with agents which reduce aqueous humor production, acetazolamide and non-anesthetic doses of phenobarbital, prevented the elevation of IOP but not the induced hypothermia. Imidazole, an agent which alters calcium kinetics, blocked the hypothermia response but not the IOP elevation.     

Treating panic symptoms within everyday clinical settings: the feasibility of a group cognitive behavioural intervention

Panic disorder is a common and debilitating disorder that has a prevalence rate of 3-5% in the general population. Cognitive-behavioural interventions have been shown to be an efficacious treatment for panic, although a limited number of studies have examined the effectiveness of such interventions implemented in everyday clinical settings. The aim of the following pilot study was to examine the feasibility of a brief group cognitive-behavioural intervention carried out in a clinical setting. Salient issues in determining feasibility include: representativeness of patient group treated, amount of significant clinical change displayed and resources required to carry out the intervention. A small sample of GP-referred patients displaying panic symptoms completed a 2-week intensive cognitive-behavioural intervention. Results collected post-intervention revealed significant clinical reductions in panic, anxiety and depressive symptoms and marked improvement in mobility. These improvements were maintained at 12-month follow-up. Outcomes supported the feasibility of a brief group cognitive-behavioural intervention for GP-referred patients. Implications of these results are discussed in terms of implementing effective treatments in everyday clinical practice and developing a stepped care approach to treating panic symptoms.     

High dosage haloperidol therapy in chronic schizophrenic patients: A double-blind study of clinical response,side effects,serum haloperidol,and serum prolactin

In a 12-weeks double-blind study high dosage versus standard dosage haloperidol therapy was evaluated in 23 male, chronic schizophrenic inpatients. The patients were relatively treatment-resistant and, in spite of traditional neuroleptic medication, were characterized by a moderate to severe degree of illness. At the end of the trial the dose of haloperidol in the standard dosage group was 12–36 mg/day (mean 15), in the high dosage group 10–240 mg/day (mean 103). No significant difference in therapeutic effect was found between the two groups as measured by the Brief Psychiatric Rating Scale and global assessment. About half the patients in both groups improved during the trial. A greater incidence of side effects was noticed in the high dosage group than in the standard group, especially in the form of sedation (5 of 12 patients), aggressive episodes (three patients), muscular weakness and tendency to fall (two patients), and epileptic attacks (one patient). The incidence of extrapyramidal phenomena showed fewer differences between the two groups. In addition, the high dosage group showed a temporary rise in serum alkaline phosphatase and serum aspartate-aminotransferase. There was a positive correlation between the dose of haloperidol and serum haloperidol, and between the haloperidol dose of up to 80 mg/day and serum prolactin. At higher doses prolactin response leveled off. Neither serum haloperidol nor serum prolactin showed any correlation to clinical response. It is concluded (1) that very high doses of haloperidol in only a few cases show any therapeutic advantage over haloperidol in standard doses; (2) that high dosage treatment has a higher incidence of side effects; and (3) that the serum concentrations of a given neuroleptic and of prolactin are of very limited value in the monitoring of neuroleptic treatment.     

Increased intraocular pressure after third ventricle injections of prostaglandin E1 and arachidonic acid.

Prostaglandin E1 administered into the third ventricle of rabbits produced increased intraocular pressure and body temperature. Similar responses were observed after third ventricle instillation of arachidonic acid, a precursor of prostaglandin E2. Increase of body temperature occurred with lower doses of prostaglandin E1 and arachidonic acid while the intraocular pressure response required larger amounts of these drugs. Pretreatment with aspirin rectal suppositories had no effect on the third ventricle responses induced by prostaglandin E1. Aspirin pretreatment before third ventricle instillation of arachidonic acid blocked the increases of intraocular pressure and temperature.     

Quantitative vitreous fluorophotometry. A sensitive technique for measuring early breakdown of the blood-retinal barrier in young diabetic patients

Vitreous and aqueous humor fluorescein concentrations were measured one hour after graded intravenous fluorescein was given to 20 juvenile diabetics, ages 20 to 40, with and without retinopathy, and to 12 controls of similar age. Vitreous fluorescein concentrations were significantly higher in diabetics, indicating breakdown of the blood-retinal barrier. Mean vitreous fluorescein values were 10.66 +/- 0.65 for the diabetics and 4.28 +/- 0.37 ng./ml. for the controls. Breakdown of the blood-retinal barrier was also confirmed in diabetics under the age of 20 without retinopathy. The blood-aqueous barrier was similarly altered in diabetics. Vitreous fluorophotometry quantitatively measures breakdown of the blood-retinal barrier, possibly the earliest detectable ocular vascular abnormality in juvenile diabetic patients.     

Ocular fluorophotometry in streptozotocin diabetes mellitus in the rat: effect of pancreatic islet isografts.

Fluorophotometry was used to evaluate the integrity of the blood-ocular barriers to fluorescein in experimental diabetes mellitus in rats. This technique allowed quantitation of ocular fluorescein concentrations following intravenous injection. Streptozotacin-induced diabetes resulted in an increased fluorescein accumulation in the anterior chamber (1.52 +/- 0.17 microgram/ml, mean +/- S.E.M.) and vitreous (0.82 +/- 0.11) over baseline nondiabetic levels (0.68 +/- 0.80 and 0.40 +/- 0.03, respectively). Fluorophotometry was repeated at 5, 13, and 20 days following portal vein pancreatic islet transplantation. At 5 days anterior chamber (1.40 +/- 0.17) and vitreous (0.61 +/- 0.08) fluorescein concentrations remained elevated. However, at 13 and 20 days following islet transplantation, ocular fluorescein concentrations were identical to levels observed prior to the induction of diabetes. Intravenous glucose (0.5 gm/kg) tolerance testing was performed 5 and 13 days following transplantation. The glucose responses to the tolerance test were normal and similar at both times. However, at 5 days the insulin response was abnormal with a decreased initial peak and an absent second peak. At 13 days there was a normal biphasic insulin response. In experimental diabetes mellitus ocular vascular permeability was more closely correlated with insulin than blood glucose abnormalities.