Systematic review processes and the management of opioid withdrawal.

OBJECTIVE: To assess the diversity of research on the management of opioid withdrawal, identify sources of heterogeneity and provide a context for subsequent systematic reviews to establish evidence-based best practice. METHODS: References were identified through searches of multiple electronic databases and handsearching the reference lists of retrieved articles. The principal criterion for inclusion in the literature mapping process was that it be a study of an intervention intended to manage the process of opioid withdrawal. RESULTS: Of 218 references assessed, all participants were dependent on heroin in 41% and on methadone or l-alpha acetyl methadol (LAAM) in 24%. More than 17 different types of treatment approach were identified. Only 42% of references used a rating instrument to assess withdrawal severity and reported sufficient results to indicate the timing and magnitude of the peak and/or duration of withdrawal. The type of rating instrument used and the way in which results were reported varied enormously. A clear parameter for completion of detoxification was used for 37% of references. CONCLUSIONS: The capacity for rigorous systematic reviews of the management of opioid withdrawal is currently limited. There are multiple sources of heterogeneity that will need to be taken into account. IMPLICATIONS: The use of narrative reviews and observational studies are important complements to formal systematic reviews in the establishment of evidence-based practice in any area that combines aspects of psychology, behaviour, social context and medical treatment.

Therapeutic use of cannabis: clarifying the debate.

The debate regarding therapeutic use of cannabis is being confused by a lack of distinction between therapeutic and social use of cannabis. Separate consideration of therapeutic and social use would enable strategies to minimise any negative social impact of therapeutic use. For therapeutic use of cannabis to be considered on its own merits, greater emphasis needs to be placed on scientific evidence of therapeutic efficacy. At present the evidence is limited, it mostly relates to the use of synthetic cannabinoids, and much of it fails to compare cannabis with the best therapies available for the conditions of interest. Claims of therapeutic efficacy tend to be based on opinion and anecdote rather than the results of controlled studies. Further research is needed to clarify the potential therapeutic benefits, to enable claims of therapeutic use to be objectively assessed and to enable informed decisions to be made about the relative risks and benefits for any individual using cannabis for therapeutic purposes. Further research is required to clarify the efficacy of pure, synthetic cannabinoids compared to cannabis, the most effective route of administration, and the importance of delivering a known dose. The most likely value of cannabis is as an adjunct, rather than a replacement for, current medical approaches. The potential therapeutic benefits of cannabis will be greatest for those conditions where long-term cannabis use, with its attendant health risks, is not an issue and where the patient has the capacity to titrate dose against symptoms. There is sufficient evidence of potential therapeutic benefit to justify the facilitation of further research.

Actin synthesis in tumorigenic and non-tumorigenic human hybrid cells.

We have previously shown that the total actin content of tumorigenic HeLa/fibroblast somatic cell hybrids is significantly lower than that of the non-tumorigenic hybrid cells. A measure of actin synthesis, relative to total protein synthesis, was obtained for these cells to determine whether the reduced actin content of the tumorigenic cells is due to specific suppression of actin synthesis. Actin synthesis was measured in cells labelled with [35S]methionine using DNase I affinity chromatography to isolate the actin quantitatively. The results show that actin synthesis is not specifically suppressed, since the relative amount of actin synthesized is constant for the tumorigenic and non-tumorigenic cell lines. The reduced actin content of the tumorigenic cells is therefore most likely to be the result of increased degradation of actin.

Mg2+ adenosine triphosphatase from cell envelopes of free-living and bacteroid forms of Rhizobium lupini strain NZP2257.

A procedure for the purification of Mg2+ adenosine triphosphatase (EC 3.6.1.3) from free-living and bacteroid forms of Rhizobium lupini NZP2257 is described. The enzyme was released from cell envelopes using Triton X-100 and purified by gel filtration on Ultrogel AcA 22, followed by preparative gel electrophoresis on agarose. The purified ATPase had a molecular weight of about 355,000, as determined from sedimentation coefficients on sucrose gradients. Kinetic analysis of activity of the enzyme from free-living R. lupini showed it to be typical of F1-type Mg2+ ATPases from bacteria. Mg stimulated activity at pH 7.0, although, when present as the free ion, Mg caused non-competitive inhibition (K1 = 1.5 mM). Maximum activity with ATP occurred over a broad pH range from 6.0 to 10.5. ATP, GTP, and UTP, and, to a much lesser degree, CTP and ADP, were hydrolyzed by the enzyme. Hydrolysis of glucose 6-phosphate was not observed. The Km for ATP at pH 7.0 was 0.67 and for GTP 1.4 mM. ATPase activity was inhibited by ADP, and competitive with ATP (KI = 0.18 mM). Azide also caused inhibition but fluoride and DCCD had no effect. Native and sodium dodecyl sulfate-gel electrophoretic analysis revealed no obvious differences between ATPases from free-living and bacteroid forms of R. lupini.

Microfilament organization and total actin content are decreased in hybrids derived from the fusion of HeLa cells with human fibroblasts.

The organization of the microfilaments and the actin content of matched pairs of tumorigenic and non-tumorigenic HeLa/fibroblast hybrid cells was compared. Each pair consisted of a hybrid cell line with suppressed tumorigenicity and a segregant tumorigenic cell line derived from it. The tumorigenic HeLa parent cell line and a non-tumorigenic human fibroblast line were also included in the comparison. Microfilament organization of the cell lines was assessed by fluorescence microscopy using NBD-phallacidin, a probe that specifically binds to actin filaments. The re-expression of tumorigenicity is associated with a loss of microfilament organization. The actin content, as measured by the DNase I inhibition assay, was significantly lower in the tumorigenic hybrids and the HeLa parent than in the non-tumorigenic cells. The comparison was significant when the actin concentration was expressed either per cell or per protein. Despite this reduced level of total actin in tumorigenic cells, the ratio of monomeric to total actin remained constant in all cell lines tested.