What is a reasonable time from decision to delivery by Caesarean section? Evidence from 533 deliveries.

Objective To determine how long it takes from the decision to achieve delivery by non-elective caesarean section (DDI), the influence on this interval, and the impact on neonatal condition at birth. Design Twelve months prospective data collection on all non-elective caesarean sections. Methods Prospective collection of data relating to all caesarean sections in 1996 in a major teaching hospital obstetric unit was conducted, without the knowledge of the other clinicians providing clinical care. Details of the indication for section, the day and time of the decision and the interval till delivery were recorded as well as the seniority of the surgeon, and condition of the baby at birth. Results The mean time from decision-to-delivery for 100 emergency intrapartum caesarean sections was 42.9 minutes for fetal distress and 71.1 minutes for 230 without fetal distress (P<0.0001). For 22 'crash' sections the mean time from decision-to-delivery was 27.4 minutes; for 13 urgent antepartum deliveries for fetal reasons it was 124.7 minutes and for 21 with maternal reasons it was 97.4 minutes. The seniority of the surgeon managing the patient did not appear to influence the interval, nor did the time of day or day of the week when the delivery occurred. Intrapartum sections were quicker the more advanced the labour, and general anaesthesia was associated with shorter intervals than regional anaesthesia for emergency caesarean section for fetal distress (P<0.001). Babies born within one hour of the decision tended to be more acidaemic than those born later, irrespective of the indication for delivery. Babies tended to be in better condition when a time from decision-to-delivery was not recorded than those for whom the information had been recorded. Conclusion Fewer than 40% intrapartum deliveries by caesarean section for fetal distress were achieved within 30 minutes of the decision, despite that being the unit standard. There was, however, no evidence to indicate that overall an interval up to 120 minutes was detrimental to the neonate unless the delivery was a 'crash' caesarean section. These data thus do not provide evidence to sustain the recommendation of a standard of 30 minutes for intrapartum delivery by caesarean section.

Design and physicochemical characterisation of a bioadhesive patch for dose-controlled topical delivery of imiquimod

Clinical use of the imidazoquinoline immunomodulator imiquimod for the topical treatment of dysplastic and neoplastic lesions has increased markedly in recent years. However, despite guidance from the manufacturer of the proprietary imiquimod cream, there seems to be little consensus between clinicians as to the topically applied dose. Given that patients often apply the cream themselves at home, further dosing variability is expected and, consequently, accurate comparison of the results of different published studies is dif?cult. This paper describes, for the ?rst time, the formulation and physicochemical characterisation of a bioadhesive patch for dose-controlled topical delivery of imiquimod as well as a new HPLC method for sensitive ?uorescence determination of imiquimod released from such systems. Patches containing imiquimod loadings of 4.75, 9.50 and 12.50 mg cm-2 all released signi?cantly more drug across a model membrane than the proprietary cream over a period of 6 h. Inclusion of imiquimod in patches did not adversely affect their physicochemical properties. Of major importance, patches contained de?ned drug loadings per unit area; therefore, their use could reduce inter-clinician variability. This would make critical comparison of clinical studies and determination of an appropriate imiquimod dose for successful treatment much simpler. Since bioadhesive formulations are capable of adhering to body tissues in moist environments, the use of a bioadhesive patch system may allow extension of the clinical uses of imiquimod to the treatment of neoplastic conditions of the oral cavity and cervix, as well as the vulva. © 2005 Elsevier B.V. All rights reserved.

Drug Delivery of Aminolevulinic Acid from Topical Formulations Intended for Photodynamic Therapy

Topical photodynamic therapy is used for a variety of malignant and pre-malignant skin disorders, including Bowen's Disease and Superficial Basal Cell Carcinoma. A haem precursor, typically 5-aminolevulinic acid (ALA), acting as a prodrug, is absorbed and converted by the haem biosynthetic pathway to photoactive protoprophyrin IX (PpIX), which accumulates preferentially in rapidly dividing
cells. Cell destruction occurs when PpIx is activated by an intense light source of appropriate wavelength. Topical delivery of ALA avoids the prolonged photosensitivity reactions associated with systemic administration of photosensitisers but its clinical utility is influenced by the tissue penetration characteristics of the drug, its ease of application and the stability of the active agent in the applied dose. This review, therefore, focuses on drug delivery applications for topical, ALA-based PDT. Issues considered in detail include physical and chemical enhancement strategies for tissue penetration of ALA and subsequent intracellular accumulation of PpIX, together with formulation strategies and drug delivery design solutions appropriate to various clinical applications. The fundamental aspects of drug diffusion in
relation to the physicochemical properties of ALA are reviewed and specific consideration is given to the degradation pathways of ALA in formulated systems that, in turn, influence the design of stable topical formulations.

Characterization of a thymidylate synthase (TS)-inducible cell line: a model system for studying sensitivity to TS- and non-TS-targeted chemotherapies

Thymidylate synthase (TS) is responsible for the de novo synthesis of thymidylate, which is required for DNA synthesis and repair and which is an important target for fluoropyrimidines such as 5-fluorouracil (5-FU), and antifolates such as Tomudex (TDX), ZD9331, and multitargeted antifolate (MTA). To study the importance of TS expression in determining resistance to these agents, we have developed an MDA435 breast cancer-derived cell line with tetracycline-regulated expression of TS termed MTS-5. We have demonstrated that inducible expression of TS increased the IC(50) dose of the TS-targeted therapeutic agents 5-FU, TDX, and ZD9331 by 2-, 9- and 24-fold respectively. An IC(50) dose for MTA was unobtainable when TS was overexpressed in these cells, which indicated that MTA toxicity is highly sensitive to increased TS expression levels. The growth inhibitory effects of the chemotherapeutic agents CPT-11, cisplatin, oxaliplatin, and Taxol were unaffected by TS up-regulation. Cell cycle analyses revealed that IC(50) doses of 5-FU, TDX and MTA caused an S-phase arrest in cells that did not overexpress TS, and this arrest was overcome when TS was up-regulated. Furthermore, the S-phase arrest was accompanied by 2- to 4-fold increased expression of the cell cycle regulatory genes cyclin E, cyclin A, and cyclin dependent kinase 2 (cdk2). These results indicate that acute increases in TS expression levels play a key role in determining cellular sensitivity to TS-directed chemotherapeutic drugs by modulating the degree of S-phase arrest caused by these agents. Moreover, CPT-11, cisplatin, oxaliplatin, and Taxol remain highly cytotoxic in cells that overexpress TS.

Client's assessment of architects' performance in building delivery process: Evidence from Nigeria

The overall intent of this research is to provide architects with information that can be used to improve their performance so as to optimally satisfy the client's requirements and achieve high-quality overall project performance in Nigerian construction industry. Architect performance criteria were identified based on literature within the domain of architect responsibilities. The assessment of architects’ performance was carried out through a questionnaire survey of clients of recently completed building projects in Nigeria. Analysis of data includes comparison of criteria using importance–performance index analysis. Factor analysis was carried out on criteria where architects are falling below average, to group and explore the latent structure of the criteria in the data. The results showed that the architect needs to focus on management skills and ability, buildability, design quality, project communication, project integration and client focus. These results would encourage architects to perform better within their full responsibilities in the building delivery process and deliver high-quality projects within Nigerian construction industry.