Markers of HIV infection in the Concorde trial. Concorde Co-ordinating Committee

The Concorde trial compared immediate (Imm) with deferred (Def) AZT monotherapy in asymptomatic HIV-positive participants. Haematological and immunological markers and weight were measured throughout, and correlated with clinical endpoints. Markers associated with disease progression (CD4 lymphocyte count and percentage, platelets, p24 antigen and beta 2 microglobulin favoured Imm: those associated with toxicity (haemoglobin, neutrophils and white cell count) favoured Def. CD8 and total lymphocyte count did not differ significantly between groups. In multivariate analysis, the combination of baseline CD4, p24 antigen and beta 2m was the best baseline predictor of disease. Including change in CD4 and beta 2m at 12 weeks, or changes over follow- up in these markers significantly improved the fit. Markers were also incorporated into the definition of 'clinical' endpoints. Hazard ratio estimates from end-points that included CD4 < 50 and CD4 < 25 were closest to those for AIDS or death alone, but added very few extra events. Use of other landmark CD4 counts (100 or greater) or relative decreases in counts (25% or more) increased the number of events, but overestimated the effect of immediate AZT. Although AZT had a beneficial effect on the surrogate markers of efficacy evaluated, these changes did not predict clinical outcome, nor could the markers be usefully incorporated into an endpoint definition.      

Imaging the 3D structure of secondary osteons in human cortical bone using phase-retrieval tomography

By applying a phase-retrieval step before carrying out standard filtered back-projection reconstructions in tomographic imaging, we were able to resolve structures with small differences in density within a densely absorbing sample. This phase-retrieval tomography is particularly suited for the three-dimensional segmentation of secondary osteons (roughly cylindrical structures) which are superimposed upon an existing cortical bone structure through the process of turnover known as remodelling. The resulting images make possible the analysis of the secondary osteon structure and the relationship between an osteon and the surrounding tissue. Our observations have revealed many different and complex 3D structures of osteons that could not be studied using previous methods. This work was carried out using a laboratory-based x-ray source, which makes obtaining these sorts of images readily accessible.     

Bladder cancer biomarkers and their role in surveillance and screening

Early detection of bladder cancer and its recurrences is essential for improved prognosis and long-term survival. The detection and follow-up of these patients is currently based on cystoscopy, which is expensive and invasive, and, in most cases, cytology, which is non-invasive but not very sensitive. During recent years, many urine-based tests have been developed and tested in different patient populations. In this review we discuss new developments for biomarkers in bladder cancer that have potential use in surveillance and screening. In almost all publications authors compare sensitivity of the test with a concomitantly executed cystoscopy, for example, determine cross-sectional sensitivity. However, it has also been shown that false positive test results may be followed by a positive cystoscopy in the near future, showing that cystoscopy itself does not provide 100% sensitivity. This suggests that for a proper evaluation of urine-based tests, longitudinal studies should be carried out and the results communicated to the urologist.     

Mediators and receptors in the resolution of inflammation: drug targeting opportunities

The active resolution of inflammation is recognized as offering new opportunities to generate novel anti-inflammatory agents. The emerging appreciation of the importance of active resolution in regulation of inflammation also creates an imperative to examine developing and existing agents for their potential to influence these pathways. This themed issue of the British Journal of Pharmacology contains papers that discuss the roles of annexin-1, lipoxins and related lipid products of fish oils as well as other mechanisms involved in active resolution and their receptor targets.This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

Histamine H1 receptor knockout mice exhibit impaired spatial memory in the eight-arm radial maze

Background and purpose:

In the mammalian brain, histaminergic neurotransmission is mediated by the postsynaptic histamine H₁ and H₂ receptors and the presynaptic H₃ autoreceptor, which also acts as a heteroreceptor. The H₁ receptor has been implicated in spatial learning and memory formation. However, pharmacological and lesion studies have revealed conflicting results. To examine the involvement of histamine H₁ receptor in spatial reference and working memory formation, H₁ receptor knockout mice (KO) were tested in the eight-arm radial maze. Previously, we found that the H₁ receptor-KO mice showed reduced emotionality when confronted with spatial novelty. As it is known that emotions can have an impact on spatial learning and memory performance, we also evaluated H₁ receptor-KO mice in terms of emotional behaviour in the light–dark box.

Experimental approach:

Mice lacking the H₁ receptor and wild-type mice (WT) were tested for spatial reference and working memory in an eight-arm radial maze with three arms baited and one trial per day. Emotional behaviour was measured using the light–dark test.

Key results:

The H₁ receptor-KO mice showed impaired spatial reference and working memory in the radial maze task. No significant differences between H₁ receptor-KO and WT mice were observed in the light–dark test.

Conclusions and implications:

The spatial memory deficits of the H₁ receptor-KO mice might be due to the reported changes in cholinergic neurochemical parameters in the frontal cortex and the CA1 subregion of the hippocampus, to impaired synaptic plasticity in the hippocampus, and/or to a dysfunctional brain reward/reinforcement system.     

Regional radiotherapy versus an axillary lymph node dissection after lumpectomy: a safe alternative for an axillary lymph node dissection in a clinically uninvolved axilla in breast cancer. A case control study with 10 years follow up

Background

To correlate the metabolic changes with size changes for tumor response by concomitant PET-CT evaluation of lung cancers after radiotherapy.

Methods

36 patients were studied pre- and post-radiotherapy with¹⁸FDG PET-CT scans at a median interval of 71 days. All of the patients were followed clinically and radiographically after a mean period of 342 days for assessment of local control or failure rates. Change in size (sum of maximum orthogonal diameters) was correlated with that of maximum standard uptake value (SUV) of the primary lung cancer before and after conventional radiotherapy.

Results

There was a significant reduction in both SUV and size of the primary cancer after radiotherapy (p < 0.00005). Among the 20 surviving patients, the sensitivity, specificity, and accuracy using PET (SUV) were 94%, 50%, 90% respectively and the corresponding values using and CT (size criteria) were 67%, 50%, and 65% respectively. The metabolic change (SUV) was highly correlated with the change in size by a quadratic function. In addition, the mean percentage metabolic change was significantly larger than that of size change (62.3 ± 32.7% vs 47.1 ± 26.1% respectively, p = 0.03)

Conclusion

Correlating and incorporating metabolic change by PET into size change by concomitant CT is more sensitive in assessing therapeutic response than CT alone.     

Liquidation wahlärztlicher Leistungen

Ohne Zusammenfassung     

Kosten einer Bioresonanztherapie bei Asthma bronchiale und Allergien

Abstrakt 1. Hinsichtlich der Frage der Anerkennung einer Heilmethode kommt es nicht darauf an, ob eine Methode von der überwiegenden Mehrheit der sogenannten Schulmediziner anerkannt wird, aber auch nicht, ob die betreffende Methode „therapieimmanent“, also von denjenigen, die diese Methode entwickelt haben oder sie anwenden, als wirksam eingesch?tzt wird. Entscheidend ist vielmehr auf die Anerkennung derjenigen Personen abzustellen, die sich von dritter Seite als Wissenschaftler in einem wissenschaftlichen Verfahren mit der Frage der Wirksamkeit der betreffenden Methode auseinandergesetzt haben. 2. Der Wirkmechanismus der Bioresonanztherapie ist nach strengen naturwissenschaftlichen Untersuchungen nicht zu erkl?ren. Diese Methode ist jedoch von der Hufelandgesellschaft, die sich aus 25 ?rztegesellschaften zusammensetzt, die allesamt auch Naturheilverfahren betreiben, anerkannt. (Leits?tze des Bearbeiters)