Pharmacokinetics of the acetylcholinesterase oxime reactivator, HI-6, in rhesus monkeys (Macaca mulatta): effect of atropine, diazepam, and methoxyflurane anesthesia

The pharmacokinetics of the bispyridinium oxime HI-6 (CAS reg. no. 34433-31-3; 1-(((4-aminocarbonyl)pyridinio)methoxy)methyl)-2-[hydroxy i mino)methyl)- pyridinium dichloride) was investigated in rhesus monkeys (Macaca mulatta). The effects of methoxyflurane anesthesia, administration of atropine with and without diazepam were determined on the serum half-life (t1/2), clearance rate (CL), and the volume of distribution (Vd) following intramuscular (IM) administration of HI-6 (30 mg kg-1). The control t1/2, CL and Vd of HI-offere 27 min, 8.6 ml min-1 kg-1 and 0.34 l kg-1, respectively. These parameters were unaffected by the co-administration of either atropine (0.5 mg kg-1, IM) or atropine and diazepam (0.5 mg kg-1, IM + 0.2 mg kg-1 IV, respectively). Methoxyflurane anesthesia resulted in a significant increase in the HI-6 t1/2 to 61 min concomitant with a decrease in the CL to 4.1 ml min-1 kg-1 with no change in the Vd. The increase in the t1/2 of HI-6 in methoxyflurane anesthetized monkeys is probably the result of a decrease in the clearance rate and, thus, excretion of HI-6 by the kidneys.     

Prostatectomy in a district hospital.

In order to monitor the safety and efficacy of a new service for transurethral prostatectomy, an audit was performed, prospectively, over a period of 7.25 years. Of 304 prostatectomies performed, 91% were by transurethral prostatectomy. The proportion of patients with retention was 52%, 16% were uraemic and the incidence of carcinoma of the prostate was 21%. The operative mortality rate was 1.0%. An outline of the treatment policy and the data on complications and revision operations are presented. Comparisons are made with the experience of teaching centres and other district hospitals. Transurethral prostatectomy can be performed safely in the district general hospital and is a service which is essential to the smooth running of the surgical department.     

CORRELATION OF IMMUNOLOGICAL SURFACE ANTIGENS WITH SURVIVAL IN DIFFUSE LARGE CELL LYMPHOMA

The prognostic value of immunophenotyping lymphomas with a panel of monoclonal antibodies (Mab) to various lymphoid antigens was assessed by studying 47 cases of diffuse large cell lymphoma. Cell suspensions were analysed by flow cytometry after labelling by indirect immunofluorescence. Thirty-eight cases were demonstrated to be of B cell and nine of T cell phenotype. Univariate analysis demonstrated that survival was significantly longer in patients expressing higher levels of HLA-DR (p=0·01) and normal levels of CD8 (p=0·04) but was not significantly associated with any of the other antigens. Our results support the possible value of HLA-DR in determining the prognosis of patients with diffuse large cell lymphoma.     

Azelastine inhibits agonist-induced electromechanical activity in canine tracheal muscle

We examined the effects of a new antiasthmatic drug, azelastine, on the electromechanical responses of airway smooth muscle to histamine, acetylcholine (ACh), and tetraethylammonium (TEA). Membrane potential and isometric force were simultaneously measured in isolated canine tracheal muscle using intracellular microelectrodes and a microforce transducer. Azelastine, at 1 microM, depressed the histamine-induced contractile force by more than 60 percent. The histamine-induced membrane depolarization was also inhibited, but to a much less extent, compared to the inhibition of contractile force. Similarly, contraction induced by ACh was inhibited by azelastine. In contrast to histamine, ACh elicited electrical oscillations concomitant with the membrane depolarization. Azelastine abolished these oscillations without affecting the depolarization. Azelastine inhibited the Ca2+-dependent slow action potentials (induced by 20 mM TEA) in a concentration-dependent manner; complete inhibition occurred at 30 microM. Such direct inhibitory effects of azelastine on agonist-induced airway muscle contraction may explain its ability to exert bronchodilatation in asthmatic patients. One of its mechanisms of action may involve inhibition of voltage-sensitive Ca2+ influx across the muscle cell membrane; however, additional actions intracellularly are possible.     

Command hallucinations among Asian patients with schizophrenia.

OBJECTIVES: The impact of command hallucinations on patients and the determinants of patients' compliance with them are still poorly understood. The extant literature is also divided on their association with violence. This study aimed to establish the prevalence of command hallucinations and to identify the factors that affect compliance with the commands, together with patients' coping methods. METHODS: We recruited 50 consecutive male and 50 consecutive female schizophrenia inpatients who reported hearing voices in the 6 months prior to admission. We interviewed these patients, using a semistructured questionnaire. We collected information on the contents of their auditory hallucinations and their coping methods. RESULTS: Of the patients, 53 (53%) reported command hallucinations. Of these 53 patients, 58% were women and 48% were men; 62% reported complying with the commands. They were also more likely to comply with nonviolent commands. A history of self-harm predicted compliance. Those patients who did not comply with the commands adopted various methods of coping, of which praying was the most common. CONCLUSION: Command hallucinations are common in patients with schizophrenia. Patients with a history of self-harm need closer monitoring because they may be more likely to comply with these hallucinations. Assessment should also include the patient's own coping strategies, which can be incorporated into the treatment.     

Practice‐based evidence: benchmarking NHS primary care counselling services at national and local levels

There are a number of problems for evidence‐based practice (EBP) including limited generalizability of efficacy research results, the consequent lack of confidence in the relevance of such research, and the conceptual distance of most practitioners from the research process. The result is that EBP, although sound in principle, often fails to achieve its aim of improving practice. Practice‐based evidence (PBE) provides a complementary bridge for the gap between research and practice to offset some of these problems, promoting collaboration between mental health services and academic institutions. This paper presents the initial results of such a collaboration via three phases: (1) the development of a referential database for primary care counselling services, (2) ‘practitioner‐friendly’ feedback on grouped data to services, and (3) the combination of the two to build an evidence base for work with ethnic minorities—an area in which research trials are not well adapted to provide much evidence. Copyright © 2003 John Wily & Sons, Ltd.