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At least 91 records · Page 5Linked to original sources
PubMed1998

Practice nurses and the effects of the new general practitioner contract in the British NHS: the advent of a professional project? National Health Service.

In the light of changes to the GP Contract in the U.K. which were implemented in April 1990, health promotion was introduced into General Practice and was encouraged through the financial elements of the contract. This paper seeks to illustrate some of the outcomes of the changes, in particular the extent to which activity in relation to health promotion has been passed to practice nurses. The paper explores the perceptions of the practice nurses to their new activity and examines the implications of that change. The argument is presented that health promotion activity has provided an impetus for the attempts to develop a professional project on the part of practice nurses. The outcome of that professional project and the possibility of more development of the terms of the GP Contract could lead to unintended consequences of change in General Practice and the paper argues the need for more evaluation and debate of the developments.

Health Promotion↗
PubMed2003

Evolution of eukaryotic cell cycle regulation: stepwise addition of regulatory kinases and late advent of the CDKs.

Protein kinases regulate a number of critical events in mitosis and meiosis. A study of the evolution of kinases involved in cell cycle control (CCC) might shed light on the evolution of the eukaryotic cell cycle. In particular, applying quantitative phylogenetic methods to key CCC kinases could provide information on the relative timing of gene duplication events. To investigate the evolution of CCC kinases, we constructed phylogenetic trees for the CDC28 family and performed statistical tests of the tree topology. This family includes the cyclin-dependent kinases (CDKs), which are key regulators of the eukaryotic cell cycle, as well as other CCC kinases. We found that CDKs and, in particular, the principal cell cycle regulator Cdc28p, branch off the phylogenetic tree at a late stage, after several other kinases involved in either mitosis or meiosis regulation. On the basis of this tree topology, it is proposed that, at early stages of evolution, the eukaryotic cell cycle was not controlled by CDKs and that only a subset of extant kinases, notably the DNA damage checkpoint kinase Chk1p, were in place. During subsequent evolution, a series of duplications of kinase genes occurred, gradually adding more kinases to the CCC system, the CDKs being among the last major additions.

Animals↗
PubMed2003

Cholecystectomy in a predominantly African population before and after the advent of the laparoscopic technique.

OBJECTIVE: There is a paucity of information on gallbladder disease in an African population. We, therefore, conducted a study to compare the immediate pre-laparoscopic era with the laparoscopic period in the predominantly African population at the King Edward VIII Hospital. MATERIAL AND METHODS: Data from a retrospective analysis of 144 patients undergoing open cholecystectomy (OC) between January 1990 and December 1992 were compared with a prospective analysis of 156 patients who underwent laparoscopic cholecystectomy (LC) between February 1992 and December 1994. Demographic data, presentation, operative management and outcome were the main factors analysed. RESULTS: Eighty-two per cent were Black African and the rest of Indian origin. Endoscopic retrograde cholangiopancreatography (ERCP) confirmed ductal stones in 11 patients in the OC and nine patients in the LC group. Endoscopic duct clearance was achieved in three and nine patients, respectively. Non biliary complications were rare. There were two major duct injuries in the OC group and one cystic duct leak in the LC group. The high conversion rate of 17.9% attests to the severity of their chronic disease making safe dissection in Calot's triangle problematic. The mortality in patients undergoing OC was 1 (0.07%) and 0% for LC. In South Africa, the hospital prevalence of calculous disease in African patients is increasing. However, cholecystectomy may be safely performed. CONCLUSION: The absence of any mortality and any major duct injury in the LC group allude to the safety of this procedure when appropriately applied to this population group.

Adolescent↗
PubMed2026

Targeting DNA Methylation: New Paradigms and the Advent of Gene-Selective Tools.

DNA methylation can function as a toxic alkylation reaction exploited by chemotherapeutic agents to induce cancer cell death. However, finely tuned DNA methylation plays a fundamental role in cellular physiology, particularly in the epigenetic regulation of gene expression. Once thought to act solely as a repressor of gene transcription, its functional role has since been elucidated as genomic locus-specific and deeply connected with other epigenetic factors. Following the clinical approval of DNA methyltransferase inhibitors, such as Azacitidine and Decitabine, for the treatment of hematological malignancies, considerable efforts have been devoted to developing pharmacological tools that modulate epigenetic DNA methylation. However, the lack of gene selectivity in these agents limits their therapeutic efficacy and increases off-target toxicity. Moreover, the non-gene-selective nature of current DNA methylation-targeting molecules fails to meet the standards required to discern the nuanced roles of DNA methylation across diverse pathophysiological contexts and genomic loci, particularly in an era where next-generation sequencing and omics technologies enable high-resolution epigenetic analyses. In this review, we examine the mechanisms and roles of DNA methylation in epigenetic regulation, evaluate the current landscape of DNA methylation modulators, from traditional DNMT inhibitors to cutting-edge CRISPR-dCas9 fusion systems and protein-protein interaction disruptors, and discuss their clinical relevance. Finally, we emphasize the need for precise, locus-specific tools to advance both cancer research and therapeutic strategies.

Humans↗
PubMed2001

Mass analysis at the advent of the 21st century.

There have been many new and exciting developments in mass spectrometer systems in recent years. Many of these developments are being driven by challenges presented by molecular biology. The activity is fueled by resources being devoted to drug development, for example, and other medically and biologically related activities. Progress in these applications will be accelerated by improved sensitivity, specificity, and speed. In mass spectrometry, this translates to greater mass resolving power, mass accuracy, mass-to-charge range, efficiency, and speed. It is safe to say that the demands resulting from current analytical needs are likely to be met to varying degrees but probably not by a single analyzer technology or hybrid instrument. On-line and/or off-line separations and manipulations combined with mass spectrometry will also play increasingly important roles. For any analyzer, or combination of analyzers, to become widely used it must have an important application for which its figures of merit are best suited, relative to competing approaches. The relative cost of competing technologies is also an important factor. The mass filter has seen so much use in the past 30 years because its characteristics best fit a wide range of applications. As an example, biological applications, which are currently driving many instrument development activities in mass spectrometry, demand more information, of higher quality, from less material, faster, and at lower cost. Which technologies will dominate biological applications in the coming years is open to speculation. However, in considering the relative merits of today's dominant mass analyzers, areas of opportunity for improvement are apparent. Furthermore, new and more demanding measurement needs are constantly being recognized that will continue to exercise the creativity of the mass spectrometry community.

Journal Article↗
PubMed1996

The advent of the "unpatients'.

Predictive diagnosis by molecular methods will change the scientific basis of prognostics. At the same time, it will change the ethical dimensions of the relation among patients, their doctors and other providers of care.

Clinical Medicine↗