Interphase Clinical Trials: Phase III/Phase IV

In this paper we investigate ways in which the results of a controlled Phase III clinical trial can be used in subsequent Phase IV, and possibly further Phase III studies. Specifically we are interested in; 1) developing particular hypothesis relating to a modified study population, 2) studying how changes in the particularities of the Phase III study group can influence certain outcome variables of interest and 3) using the results of the Phase III study applied to specific target groups, having particular characteristics, to updating observations from the Phase III study with information obtained at a later stage. These issues are all concerned with the way in which we can exploit information from a Phase III trial, information that is of high quality but not necessarily directly related to the way in which many post Phase III studies, focussing on different patient population groups, are carried out. Since it is often these post Phase III studies that have the strongest influence on clinical practice we aim to develop a framework around which the post Phase III studies might be structured.     

微生物生活周期中的一个新的时期——长期稳定期

传统的对微生物生长时期的认识一般分为4个时期:迟缓期、对数期、稳定期、死亡期。实际上,这种划分不足以使我们认识到微生物生长过程的全貌。近年来许多研究表明,在死亡期之后存在一个完全不同意义的时期——长期稳定期。这个时期可能与微生物在环境中的生存状态更加相似。微生物细胞通过突变得以生存,并在选择中形成稳定期生长优势表型,深入研究微生物长期稳定期具有极其重要的意义。     

Vanadium in diabetes: 100 years from Phase 0 to Phase I

A little over one hundred years ago, a vanadium-containing compound was assessed clinically for use in treatment of human diabetic patients. The results were somewhat ambiguous, but nonetheless, intriguing. In 2000, the first Phase I clinical trial of a designed vanadium-based pharmaceutical agent (bis(ethylmaltolato)oxovanadium(IV), BEOV), was completed by Medeval Ltd., Manchester, UK. Results here, too, were promising, but not without some difficult remaining questions. In this review, we look back at the many questions asked and answered regarding vanadium’s glucose-enhancing potential, its biodistribution and biomolecular transformation, and its mechanism(s) of action, and consider some of the newest developments in the field, including novel delivery methods for vanadium in diabetes treatment.     

Phase Microscopy in Bacteriology

The function and use of the phase microscope is described for controlling the contrast in the image and making visible unstained, living microorganisms and cytological details within them. The miscroscope may be used to examine unstained, growing cultures in Petri dishes, even with the oil immersion lens. Flagella are shown on the living spore of Ashbya. Since microorganisms show sharp edges under the phase microscope, measurement of unstained living cells is now possible. B. megatherium was found to average 1.0μ in width and B. cereus 1.1 μ in width with very small variation. Observations on locomotion are like those reported by Pijper. Stained preparations of low contrast may be seen with considerably enhanced contrast by phase microscopy.     

Phase variations inBifidobacterium animalis

Strains isolated from rabbit, chicken, and rat feces and from sewage and fermented milk products, all identified asBifidobacterium animalis, were found to show phase variations in colony appearance and in cellular morphology. The rate of transition in a switching system from opaque to transparent colonies and vice versa was determined. Differences in protein components and in penicillin-binding proteins (PBPs) of the cells from different colony types are shown.     

Phase change enzyme immunoassay

A novel enzyme-linked immunoassay employing a partitioning chromophore was developed. The assay system consisted of an aqueous phase and an immiscible organic solvent. Antigen-antibody interaction was indicated by transfer of a chromogenic indicator from the aqueous phase to an organic layer. The indicator employed was a water-soluble phosphate ester of phenylazophenol. Hydrolysis of the ester by acid or alkaline phosphatase produced a water-insoluble phenol that partitioned into toluene. The enzyme employed in this assay format can be covalently linked to antibody or a specific antibody for the phosphatase can be used. Phase change immunoassays were developed for the measurement of alkaline phosphatase, human IgG in whole blood, and the human tumor marker prostatic acid phosphatase. Solid supports of small polystyrene latex particles and Sephadex were employed.