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Published Review (published + review)
Selected AbstractsClinical Pharmacokinetics of the PDT Photosensitizers Porfimer Sodium (Photofrin), 2-[1-Hexyloxyethyl]-2-Devinyl Pyropheophorbide-a (Photochlor) and 5-ALA-Induced Protoporphyrin IXLASERS IN SURGERY AND MEDICINE, Issue 5 2006David A. Bellnier PhD Abstract Background and Objectives Photodynamic therapy (PDT) uses a photosensitizer activated by light, in an oxygen-rich environment, to destroy malignant tumors. Clinical trials of PDT at Roswell Park Cancer Institute (RPCI) use the photosensitizers Photofrin, Photochlor, and 5-ALA-induced protoporphyrin IX (PpIX). In some studies the concentrations of photosensitizer in blood, and occasionally in tumor tissue, were obtained. Pharmacokinetic (PK) data from these individual studies were pooled and analyzed. This is the first published review to compare head-to-head the PK of Photofrin and Photochlor. Study Design/Materials and Methods Blood and tissue specimens were obtained from patients undergoing PDT at RPCI. Concentrations of Photofrin, Photochlor, and PpIX were measured using fluorescence analysis. A non-linear mixed effects modeling approach was used to analyze the PK data for Photochlor (up to 4 days post-infusion; two-compartment model) and a simpler multipatient-data-pooling approach was used to model PK data for both Photofrin and Photochlor (at least 150 days post-infusion; three-compartment models). Physiological parameters were standardized to correspond to a standard (70 kg; 1.818 m2 surface area) man to facilitate comparisons between Photofrin and Photochlor. Results Serum concentration-time profiles obtained for Photofrin and Photochlor showed long circulating half-lives, where both sensitizers could be found more than 3 months after intravenous infusion; however, estimated plasma clearances (standard man) were markedly smaller for Photofrin (25.8 ml/hour) than for Photochlor (84.2 ml/hour). Volumes of distribution of the central compartment (standard man) for both Photofrin and Photochlor were about the size (3.14 L, 4.29 L, respectively) of plasma volume, implying that both photosensitizers are almost 100% bound to serum components. Circulating levels of PpIX were generally quite low, falling below the level of instrument sensitivity within a few days after topical application of 5-ALA. Conclusion We have modeled the PK of Photochlor and Photofrin. PK parameter estimates may, in part, explain the relatively long skin photosensitivity attributed to Photofrin but not Photochlor. Due to the potential impact and limited experimental PK data in the PDT field further clinical studies of photosensitizer kinetics in tumor and normal tissues are warranted. Lasers Surg. Med. © 2006 Wiley-Liss, Inc. [source] Inguinal hernia repair: Where to next?ANZ JOURNAL OF SURGERY, Issue 8 2002Martina Zib Background: Hernia repair is one of the most frequently performed operations in general surgery , a total of 39 000 elective inguinal hernia repairs were performed in public and private hospitals in Australia between July 1998 and June 1999 , and, as such, even minor alterations in outcome and resource use have appreciable impact. However, decisions regarding choice of operation for hernia repair remain controversial. The purpose of the present paper is to critically evaluate the evidence available regarding recently introduced open mesh repair techniques and to try to identify meaningful directions for future hernia research. Methods: A thorough search of all published surgical literature was undertaken. Medline, EMBASE and the Cochrane databases were searched by title, by key words and by author. References in review articles and in textbooks were pursued. The manufacturing companies were contacted for trials evaluating their product. Results: Eight original articles evaluating either the Kugel Patch, the PerFix Plug or the Prolene Hernia System were located. None of these trials directly compared two or more of these repair systems. To date, there has been no published review of the evidence regarding the newer mesh repair techniques. With one exception, all of these articles qualify as Level IV evidence. Highlighted is the lack of evidence regarding chronic significant posthernioplasty pain , this has an incidence of 6,12%. This complication is 3,5 times more common than recurrence after open repair, is clinically relevant, is poorly understood and has been poorly studied. Arguably it is a more important end point than recurrence. Conclusion: Only one study comparing the newer techniques of open hernia repair (PerFix Plug) constitutes Level II evidence. The PerFix Plug appears to be quicker to insert and uses a smaller incision. Chronic significant posthernioplasty pain is a more important endpoint in hernia research than is recurrence, and this review concludes with a proposal for a multicentre, randomized, controlled trial evaluating the incidence of chronic significant posthernioplasty pain following elective mesh repair of primary, unilateral hernias. [source] The impacts of non-native species on UK biodiversity and the effectiveness of controlJOURNAL OF APPLIED ECOLOGY, Issue 5 2000Sarah J. Manchester 1.,The introduction of non-native species continues to cause ecological concern globally, but there have been no published reviews of their effects in the UK. Impacts in the UK are therefore reviewed, along with current legislation and guidelines relating to the introduction and control of such species. 2.,A large number of non-native species have been introduced to the UK, both deliberately and accidentally, but only a small number of introduced non-native species have established and caused detrimental ecological impacts. However, general declines in UK biodiversity, and the potential effects of future climate change, may increase the susceptibility of ecosystems to invasions. 3.,Detrimental impacts of non-native species on native biota have occurred through competition, predation, herbivory, habitat alteration, disease and genetic effects (i.e. hybridization). There are potential effects on genetic biodiversity as well as species biodiversity. 4.,Several high profile examples highlight the technical difficulties, and financial implications, of removing an introduced species once it is established. Few UK control or eradication programmes have been successful. 5.,Control might be more feasible if ,problem' species could be identified at an earlier stage of establishment. However, the poor success of attempts to characterize invasive species and predict which will have negative impacts highlight the individual and unpredictable nature of invasions. The difficulties of making general predictions suggest that every proposed species introduction should be subject to rigorous ecological characterization and risk assessment prior to introduction. 6.,The plethora of UK legislation and guidelines developed to reduce impacts of non-native species only go part of the way towards ameliorating impact. Many species already established in the wild might cause future problems. Illegal releases and escapes of non-native species may augment feral populations or establish new colonies. While regulation of imports and releases is important, further enforcement of existing legislation and action against unlicensed releases is necessary. [source] Caries-preventive effect of resin-based and glass ionomer sealants over time: a systematic reviewCOMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY, Issue 6 2006N. Beiruti Abstract,,, Introduction:, The difference in preventing dentine lesion development between resin-based and glass ionomer sealant materials is unclear. Two recently published reviews were unable to conclude on the difference because the comparison was an exclusion criterion in one review and there were statistical shortcomings in the relevant papers in the other (Cochrane) review. Objectives:, The aim of the present investigation was to carry out a systematic review on the caries-preventive effect of these two types of sealant materials under more liberal exclusion criteria concerning the statistical presentations in the publications. Methods:, Based on five exclusion criteria, the literature search in the electronic libraries PubMed and MEDLINE and the publications retrieved in the Cochrane review, revealed 12 eligible publications for analyses. A variety of glass ionomers and resin-based sealant materials had been applied in the included studies. Attributable risk (AR) was chosen rather than relative risk (RR), as used in the Cochrane review, because RR is very instable in a low caries population. Results:, There was no consistent pattern observed with respect to the caries-preventive effect of either resin-based or glass ionomer sealants. Therefore, it was impossible to calculate an overall AR. Conclusions:, There is no evidence that either resin-based or glass ionomer sealant material is superior to the other in preventing dentine lesion development in pits and fissures over time. [source] | ||||||||||