In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet formulations: a pharmacoscintigraphic study in the beagle dog.

The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.     

Canadian Consensus Recommendations for the Optimal Use of Enfuvirtide in HIV/AIDS Patients.

BACKGROUND AND OBJECTIVES: An eight-member group consisting of Canadian infectious disease and immunology specialists and a family physician with significant experience in HIV management was convened to update existing recommendations, specifically intended for use by Canadian HIV-treating physicians, on the appropriate use of enfuvirtide in HIV/AIDS patients with resistance to other antiretroviral drugs. METHODS: Evidence from the literature and expert opinions of the group members formed the basis of the guidelines. Comments on the draft guidelines were obtained from other physicians across Canada with HIV expertise. The final guidelines represent the group's consensus agreement. RESULTS AND CONCLUSIONS: The recommendations were developed to guide physicians in optimal practices in patient selection for enfuvirtide treatment and subsequent patient management. The issues considered include positive predictors of response to enfuvirtide, stage of disease, optimization of the background regimen, early indicators of enfuvirtide response, and patient education and support.     

How Can and Do Australian Doctors Promote Physical Activity?

Background.Physical inactivity is recognized as an important public health issue. Yet little is known about doctors' knowledge, attitude, skills, and resources specifically relating to the promotion of physical activity. Our survey assessed the current practice, perceived desirable practice, confidence, and barriers related to the promotion of physical activity in family practice.Methods.A questionnaire was developed and distributed to all 1,228 family practitioners in Perth, Western Australia.Results.We received a 71% response (n= 789). Family practitioners are most likely to recommend walking to sedentary adults to improve fitness and they are aware of the major barriers to patients participating in physical activity. Doctors are less confident at providing specific advice on exercise and may require further skills, knowledge, and experience. Although they promote exercise to patients through verbal advice in the consultation, few use written materials or referral systems.Conclusions.There are significant differences between self-reports of current practice and perceived desirable practice in the promotion of physical activity by doctors. Future strategies need to address the self-efficacy of family physicians and involve resources of proven effectiveness. The potential of referral systems for supporting efforts to increase physical activity by Australians should be explored.     

Raised corticosterone in the rat after exposure to the elevated plus-maze

Rats given one or two 5-min trials in the elevated plus-maze had plasma corticosterone concentrations significantly higher than the home cage control group and there was no sign of habituation in the group given two trials. In rats given two plus-maze trials the corticosterone responses were significantly higher in the group given 10-min rather than 5-min trials. A previous experience of cat odour (1 week earlier) has no effect on the plasma corticosterone response, but did have an anxiogenic effect that could be detected by a decrease in the percentage of time spent on the open arms of the plus-maze. The results are discussed with reference to the nature of anxiety generated by trials 1 and 2 and by the trial duration in the plus-maze, and with respect to dissociation between behavioural and endocrinological measures.     

Peripheral Blood Lymphocyte Surface Antigen Expression and Prognosis in Myeloma: Australian Leukaemia Study Group Study

The Australian Leukaemia Study Group myeloma study (MM1) aimed to determine the prognostic significance of clinical and immunophenotypic markers in patients with multiple myeloma. All patients were treated with standard dose melphalan and prednisone. Seventy-four patients were entered and the median survival was 27 months. Serum beta 2-microglobulin (βM) and albumin levels were the only significant clinical factors influencing survival (p = 0.007 and p = 0.008, respectively). Patients with raised levels of CD38+ lymphocytes at presentation had a significantly shorter survival than patients with normal levels (p = 0.01, logrank test, median 19 months vs 33 months). CD38 antigen expression was independent of β2M but patients with raised levels of CD38 had significantly lower levels of albumin than patients with normal levels (p = 0.001) which may explain their poorer survival. Salmon and Durie stage was not associated with antigen expression. No other B-cell antigens (CD10, CD19, CD20, CD21, CD22, CD23, FMC1 or FMC7) or plasma cell antigens tested (PCA-1) were found to be associated with prognosis. Patients who achieved plateau phase had a better prognosis than those who did not (p = 0.04 in a landmark analysis). Patients who achieved plateau phase following an objective response appeared to have a better prognosis than those who were in plateau phase at presentation (p = 0.09 in a landmark analysis). Light chain isotype suppression (LCIS) was not associated with a significant survival advantage and did not correlate with any known prognostic indicator. We conclude that phenotypic analysis of peripheral blood lymphocytes for CD38 antigen at diagnosis may be useful as a prognostic indicator in patients with myeloma.     

Supportive employment for individuals with chronic schizophrenia: the case for a National Health Service community-based sheltered workshop

A pilot project was established from 1992 to 1994 to provide people with chronic schizophrenia living in Dundee, Scotland, with a National Health Service sheltered workshop that would be fully integrated into the local business community. Of the 43 clients who attended the sheltered workshop, 38 agreed to take part in the project. Typical attenders were single, middle-aged men with schizophrenia. Twenty-five per cent had spent more than two years in hospital; 75% had been unemployed for more than five years. The clients' use of National Health Service day facilities more than halved while attending the workshop. Their hospital readmission rates were low (16%) compared with the local readmission rates for people with schizophrenia in Dundee (86%). A training approach based on the general principles of social skills training contributed to positive vocational outcomes for one-third of the workshop clients. The findings suggest that the onus of responsibility for providing work for many individuals with schizophrenia remains with the National Health Service, and in particular, occupational therapy. Occupational therapy staff must assess their clients effectively and provide quality training leading to opportunities for paid employment. These results have implications for the training of occupational therapy staff and also for the staffing structure in sheltered workshops. Copyright © 1997 Whurr Publishers Ltd.     

Access to health care in South Africa--the influence of race and class.

OBJECTIVES: The first democratic government elected in South Africa in 1994 inherited huge inequities in health status and health provision across all sections of the population. This study set out to assess the impact of the new government's commitment to address these inequities and implement policies to improve population health in general and address inequalities in health care in particular. DESIGN: A 1998 household survey assessed many aspects of health delivery, including their own perceived and actual access to health care among different segments of South African society. RESULTS: Race was the main predictor of perceived changes in access to health care, with black, coloured-and Indian respondents significantly more likely to feel that access had improved since 1994, compared with white respondents. Socio-economic status (SES) was the main predictor of actual access to health care, with low and middle SES classes significantly less likely to access care when ill. CONCLUSIONS: One-third of respondents perceived health care access to have improved between 1994 and 1998, and this response was partially determined along racial lines. About one-quarter reported an inability to access health care when they required it, and this response was partially determined along socio-economic lines. This set of contrasting responses suggests that at a political level perceptions are largely influenced by race, but at the operational level actual access is influenced by SES.     

Conjunctival granuloma caused by surgical talc.

Talc from surgical gloves has been known to be a cause of granulomas within the surgical cavity. We report a case in which recurrent conjuntival inflammation was found to be caused by talc.