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At least 217 records · Page 12Linked to original sources

PubMed2002

Anthracyclines in the treatment of gynecologic malignancies.

OBJECTIVE: The purpose of this article is to present a summary of the pharmacology of anthracyclines as well as to review the results of clinical trials including patients with gynecologic malignancies treated with anthracycline-based therapy. METHODS: We performed a MEDLINE literature search of relevant clinical trials for the scope of this review that evaluated anthracycline-based therapy in gynecologic malignancies. RESULTS: Doxorubicin has established activity in carcinomas that arise in the ovary, uterine cervix, and endometrium as well as in uterine sarcomas. However, doxorubicin has structural characteristics that limit its efficacy and safety. Newer anthracyclines with distinct structure, pharmacokinetics, pharmacodynamics, and toxicity profiles have been developed to overcome the limitations of doxorubicin and to further exploit the activity of anthracyclines. Epirubicin is characterized by a structural formula that confers similar cytotoxic antitumor activity with fewer associated side effects than its analogue. Most recently, pegylated liposomal formulations, with distinct pharmacokinetic properties and a favorable toxicity profile, have shown antitumor activity as salvage therapy in ovarian cancer. Intraperitoneal mitoxantrone is also associated with activity in ovarian cancer; however, its clinical use is limited by the severity of local adverse effects. CONCLUSIONS: The role of anthracyclines in the management of advanced gynecologic malignancies is important as part of first-line therapy or as a salvage approach. Newer anthracycline agents such as epirubicin and pegylated liposomal doxorubicin are associated with a more favorable toxicity profile. Clinical trials are under way to further explore the role of newer anthracycline-based regimens as first-line or salvage treatment in gynecologic malignancies.

Anthracyclines↗

PubMed2004

The effectiveness of public health nursing: the problems and solutions in carrying out a review of systematic reviews.

BACKGROUND: In 1999 the Scottish Office, United Kingdom, intimated that the Chief Nursing Officer would undertake a policy review of nurses' contribution to improving the public's health. The importance of reviewing the scientific literature on the effectiveness of public health nursing was recognized as a crucial part of the policy review. A final report was expected within a 6-month period. The reason for the short time period was to fit the policy-making schedule. This paper discusses our literature review for this work. AIMS: The aim was to conduct a review of the international scientific literature that gave the greatest coverage of the role and potential role of nurses in improving the public's health in relation to 14 major health topics. This paper describes the methods used, outlines the rationale underpinning the methods, discusses the problems encountered and offers solutions to some of these problems. METHODS: The initial search for relevant scientific literature revealed 709 suitable primary papers. Reviewing this number was beyond the time limit set by the funding organization. Therefore, a decision was made to concentrate on the evidence contained in systematic reviews. Reviewing systematic reviews raises a number of methodological problems to which there are often no predetermined solutions, such as ensuring that important interventions are included, assessing the relevance and quality of the reviews, and grading the strength of the evidence. DISCUSSION: Reviewing systematic reviews provides the scope to increase the number of topics that might be covered. However, it is possible that a number of interventions may be missed, particularly those that are not subject to review or those assessed using qualitative techniques. The definition of public health nursing used in the present study was also restrictive, and could be widened to include community interventions. Finally, assessing the quality of reviews and grading the evidence proved difficult and there is lack of consensus on how these tasks should be achieved. Nevertheless, the review presented policy makers with accessible information on a large number of relevant international studies.

Delivery of Health Care↗

PubMed1988

Review: the treatment of hepatocellular carcinoma.

Surgical resection offers the only realistic hope of cure in hepatocellular carcinoma (HCC) but is usually not possible, either because the tumour is widespread throughout the liver at diagnosis, or because liver function is adversely affected by concomitant cirrhosis. The results of operation in early asymptomatic disease are, however, encouraging and efforts should be made to screen regularly the cirrhotic population at risk of HCC development. The prognosis for inoperable patients remains gloomy, though exciting new treatment methods exist which require extensive evaluation. An anthracycline given as single agent intravenous therapy is probably the current treatment of choice for inoperable patients, though only 20-30% will show a response. Intra-arterial therapy has not yet been convincingly shown to have any advantages over intravenous therapy. The evaluation of clinical trials in HCC would be made easier if response criteria were standardized and universally adopted, and if trials were properly controlled and of sufficient sample size to test adequately the hypothesis in question. This review deals only with the specific treatment of HCC. HCC prevention, the early diagnosis of HCC, and the relief of symptoms in HCC, though areas of obvious importance, are outside the scope of this review.

Carcinoma, Hepatocellular↗

PubMed2003

Diagnosis and treatment of bacterial meningitis.

This review focuses on recent advances of topical interest regarding the diagnosis and treatment of common causes of bacterial meningitis occurring in children beyond the neonatal period. Tuberculous meningitis is beyond the scope of this review.

Anti-Bacterial Agents↗

PubMed2002

Polymer-supported metal-phosphine complexes for use as catalysts or linkers in medicinally-oriented organic synthesis.

Polymer-supported catalysts and reagents have found many uses in synthetic organic chemistry. This review discusses the preparation of polymer-supported phosphine ligands and organometallic complexes formed using these and highlights their use in reactions that are of particular interest to medicinal chemists. The scope of the review is limited to phosphine ligands and their metal complexes attached to derivitised polystyrene supports.

Catalysis↗

PubMed2006

Collagen hydrolysate for the treatment of osteoarthritis and other joint disorders: a review of the literature.

BACKGROUND: There is a need for an effective treatment for the millions of people in the United States with osteoarthritis (OA), a degenerative joint disease. The demand for treatments, both traditional and non-traditional, will continue to grow as the population ages. SCOPE: This article reviews the medical literature on the preclinical and clinical research on a unique compound, collagen hydrolysate. Articles were obtained through searches of the PubMed database (www.pubmed.gov) through May 2006 using several pairs of key words (collagen hydrolysate and osteoarthritis; collagen hydrolysate and cartilage; collagen hydrolysate and chondrocytes; collagen hydrolysate and clinical trial) without date limits. In addition, other sources of information, such as abstracts presented at scientific congresses and articles in the German medical literature not available on PubMed, were reviewed and included based on the authors' judgment of their relevance to the topic of the review. FINDINGS: According to published research, orally administered collagen hydrolysate has been shown to be absorbed intestinally and to accumulate in cartilage. Collagen hydrolysate ingestion stimulates a statistically significant increase in synthesis of extracellular matrix macromolecules by chondrocytes (p < 0.05 compared with untreated controls). These findings suggest mechanisms that might help patients affected by joint disorders such as OA. Four open-label and three double-blind studies were identified and reviewed; although many of these studies did not provide key information--such as the statistical significance of the findings--they showed collagen hydrolysate to be safe and to provide improvement in some measures of pain and function in some men and women with OA or other arthritic conditions. CONCLUSION: A growing body of evidence provides a rationale for the use of collagen hydrolysate for patients with OA. It is hoped that ongoing and future research will clarify how collagen hydrolysate provides its clinical effects and determine which populations are most appropriate for treatment with this supplement.

Administration, Oral↗

PubMedDate not supplied

Current indications and techniques in evaluating inflammatory disease and neoplasia of the sinonasal cavities.

Imaging strategies of the sinonasal cavities have undergone extensive revision over the last 5-year period. The traditional imaging examination of the paranasal sinuses, plain film radiography, does reasonably well in diagnosing maxillary, frontal, and sphenoid sinusitis. However, it less reliable in depicting abnormalities in the ethmoid sinuses, the most common area first affected with inflammatory disease. Compared with sinus computed tomography (CT), plain films prove to be less specific and sensitive in depicting the extent of sinus abnormalities. One series plainly concluded that sinus radiographs were not reliable enough to be an integral part of the clinical decision process. The use of plain radiographs of the sinuses has clearly been reduced by medical cost-containment concerns, replacement by superior techniques, and by clear weaknesses of the modality. Although it is inexpensive and easily accessible, the low sensitivities and inaccuracies of plain film radiography have resulted in the current use of CT and high-field-strength (1.5 Tesla) magnetic resonance imaging (MRI). By using this cross-sectional imaging, we now visualize directly the pathologic conditions within the sinuses, as well as the normal anatomy. We discuss current use of diagnostic imaging in the evaluation of patients with nasosinusoidal complaints (most commonly resulting from acute and chronic inflammatory disease), with complications of sinonasal inflammatory disease, and with suspected/documented neoplasia. In addition to developing an imaging algorithm to provide the information affecting clinical decision making, we detail the specific imaging techniques necessary accurately to obtain that information. We also review the specific concerns about imaging patients in the intensive care unit and touch on several emerging imaging techniques. The imaging workup in pediatric patients and patients with congenital anomalies is beyond the scope of this review.

Algorithms↗

PubMed1999

Synapsins as regulators of neurotransmitter release.

One of the crucial issues in understanding neuronal transmission is to define the role(s) of the numerous proteins that are localized within presynaptic terminals and are thought to participate in the regulation of the synaptic vesicle life cycle. Synapsins are a multigene family of neuron-specific phosphoproteins and are the most abundant proteins on synaptic vesicles. Synapsins are able to interact in vitro with lipid and protein components of synaptic vesicles and with various cytoskeletal proteins, including actin. These and other studies have led to a model in which synapsins, by tethering synaptic vesicles to each other and to an actin-based cytoskeletal meshwork, maintain a reserve pool of vesicles in the vicinity of the active zone. Perturbation of synapsin function in a variety of preparations led to a selective disruption of this reserve pool and to an increase in synaptic depression, suggesting that the synapsin-dependent cluster of vesicles is required to sustain release of neurotransmitter in response to high levels of neuronal activity. In a recent study performed at the squid giant synapse, perturbation of synapsin function resulted in a selective disruption of the reserve pool of vesicles and in addition, led to an inhibition and slowing of the kinetics of neurotransmitter release, indicating a second role for synapsins downstream from vesicle docking. These data suggest that synapsins are involved in two distinct reactions which are crucial for exocytosis in presynaptic nerve terminals. This review describes our current understanding of the molecular mechanisms by which synapsins modulate synaptic transmission, while the increasingly well-documented role of the synapsins in synapse formation and stabilization lies beyond the scope of this review.

Animals↗

PubMed2006

Chemical modification and formulation approaches to elevated drug transport across cell membranes.

Drug delivery across cellular barriers, such as intestinal, nasal, buccal, alveolar, vaginal, ocular and blood-brain, is a challenging task. Multiple physiological mechanisms, such as cellular organisation, efflux, and chemical and enzymatic degradation, as well as physicochemical properties of the drug molecule itself, determine the penetration of xenobiotics across epithelial cell layers. Limited intestinal absorption of many novel and highly potent lead compounds has stimulated an intense search for strategies that can effectively enhance permeation across these biological barriers. This review discusses some of the approaches that have been, and are currently being, investigated for transepithelial drug delivery. Transdermal drug delivery requires a separate discussion on its own and is thus outside the scope of this review article.

Animals↗

PubMed1988

Clinical analysis of individual steroids by column liquid chromatography.

At present, there are various LC methods available for the determination of estriol, aldosterone, and cortisol in urine, and for cortisol, cortisone, 11-deoxycortisol, corticosterone, 17-hydroxyprogesterone, estriol, vitamin D isomers, and various exogenous glucocorticoids in serum. The LC methods are more specific than the currently available RIAs or homogenous immunoassays. However, whether the data obtained by more specific LC methods are better clinically than the commonly used immunoassays for these steroids must still be proven. In this review, I have critically evaluated various LC methods currently available for the routine determination of clinically important steroids in the clinical laboratories. A complete evaluation and advantages and disadvantages of alternative techniques are beyond the scope of this review. However, the readers are urged to refer to the review articles and chapters listed in the reference section.

Chromatography, Liquid↗

PubMed2004

Somatropin and its variants: structural characterization and methods of analysis.

Human Growth hormone (hGH, somatotrophin) is a 22 kDa, 191 amino-acid single chain protein produced by somatroph cells of the anterior pituitary gland. It is the major physiological regulator of growth, and deficiencies in growth hormone levels have long been recognized as the underlying cause of growth disorders (dwarfism). The ability of exogenous hGH to restore normal rates of growth in both human and animal models of growth retardation has long been recognized and the use of hGH in therapy goes back several decades. Initial preparations were prepared by extraction and purification from cadaveric pituitary tissue, and since 1984, hGH has been prepared by recombinant Deoxyribosenucleic acid (rDNA) technology. As is usually the case with "biologicals", characterization of the drug substance depended on a combination of physico-chemical and biological methods, and the hGH molecule became well characterized fairly early in its life as a drug. Indeed, by 1980 the major degradation forms and structural variants of the hGH molecule had been described and reviewed. Little satisfactory progress had been made in refining biological assays for hGH, and, although in vitro assays were described, potency-defining assays remained dependant on the whole body growth response in rats, and were both invasive and imprecise. In the early 1990's a series of collaborative studies on analysis of recombinant hGH (somatropin) established that available bioassays were much less selective that physico-chemical methods in detecting and quantifying structural degradation, and 1994 saw an international consensus to replace the bioassays with physico-chemical analytical methods for the routine batch release of somatropin. During the last decade in most markets somatropin has, unusually for a protein, been subject to batch release and control dependent entirely on physico-chemical analysis, without the routine use of any form of bioassay. During that time there has been a continuous development and refinement of methods, and the identification of a range of structural variants and degradation products of the molecule. The present review sets out to summarise the current knowledge on physico-chemical analytical methods for somatropin, and the structural variants that have been identified and characterized. A survey of available biological analytical methods is beyond the scope of this review, as is consideration of the earlier pituitary preparations and the recombinant 192 amino-acid methionyl form of the molecule (somatrem), although it is likely that many of the methods and variants described would be equally applicable to somatrem.

Chromatography, High Pressure Liquid↗

PubMed2005

Children with HIV: improved mortality and morbidity with combination antiretroviral therapy.

PURPOSE OF REVIEW: Advances in the management of children with vertical HIV-1 infection in the developing and developed worlds are discussed in reference to literature published in 2003/4. Studies in mother-to-child transmission are beyond the scope of this review. RECENT FINDINGS: Improvements in mortality and morbidity from HIV-1 infection following combination antiretroviral therapy are extremely encouraging. There is an increase in the understanding of the immune response to HIV-1 in infants and children and a possible future role for immunomodulatory therapies. Preliminary data are available on the timing of initiation of antiretroviral therapy, the optimization of drug combinations and the clinical interpretation of genotypic resistance testing and therapeutic drug monitoring. Evidence is emerging that early antiretroviral therapy can protect the central nervous system in infants. In resource-limited settings, mortality and morbidity remain extremely high but low-cost health interventions such as prophylactic co-trimoxazole can reduce mortality prior to the expansion of antiretroviral therapy programmes. SUMMARY: Further randomized controlled trials assessing antiretroviral therapy combinations with a sustained virological/immunological response with minimal toxicities are required. The roles of therapeutic drug monitoring and resistance testing require further elucidation. The expansion of antiretroviral therapy programmes is essential for children with HIV living in resource-limited settings.

Anti-HIV Agents↗

PubMed2003

The comorbidity of migraine.

This review addresses the methodologic issues relevant to the study of comorbidity and provides a broad overview of the medical and psychiatric conditions associated with migraine. Since the body of literature examining the comorbidity of migraine is enormous, the scope of this review will largely focus on community and case-control studies. Among the selected comorbid medical conditions, including disorders of the cardiovascular, respiratory, neurologic, gastrointestinal and immunologic systems, stroke, asthma, and allergies appear to be most strongly associated with migraine. Among the psychiatric illnesses, mood and anxiety disorders have been shown to be most strongly associated with migraine in the general population. Further research is indicated and necessary to elucidate the precise mechanism of migraine comorbidity.

Bipolar Disorder↗

PubMed2004

Intracellular proteoglycans.

Proteoglycans (PGs) are proteins with glycosaminoglycan chains, are ubiquitously expressed and have a wide range of functions. PGs in the extracellular matrix and on the cell surface have been the subject of extensive structural and functional studies. Less attention has so far been given to PGs located in intracellular compartments, although several reports suggest that these have biological functions in storage granules, the nucleus and other intracellular organelles. The purpose of this review is, therefore, to present some of these studies and to discuss possible functions linked to PGs located in different intracellular compartments. Reference will be made to publications relevant for the topics we present. It is beyond the scope of this review to cover all publications on PGs in intracellular locations.

Animals↗

PubMed2006

Molecular mechanisms of detrusor and corporal myocyte contraction: identifying targets for pharmacotherapy of bladder and erectile dysfunction.

The Post-Genomic age presents many new challenges and opportunities for the improved understanding, diagnosis and treatment of human disease. The long-term goal is to identify molecular correlates of disease processes, and use this information to develop novel and more effective therapeutics. A major hurdle in this regard is ensuring that the molecular targets of interest are indeed relevant to the physiology and/or pathophysiology of the processes being studied, and, moreover, to determine if they are specific to the tissue/organ being investigated. As a first step in this direction, we have reviewed the literature pertaining to bladder and erectile physiology/pharmacology and dysfunction and attempted to summarize some of the critical molecular mechanisms regulating detrusor and corporal myocyte tone. Because of the vast amount of published data, we have limited the scope of this review to consideration of the calcium-mobilizing and calcium-sensitizing pathways in these cells. Despite obvious differences in phenotypic characteristics of the detrusor and corporal myocyte, there are some common molecular changes that may contribute to, for example, the increased myocyte contractility characteristic of bladder and erectile dysfunction (i.e. increased Rho kinase activity and decreased K(+) channel function). Of course, there are also some important distinctions in the pathways that modulate contractility in these two cell types (i.e. the contribution of ryanodine-sensitive calcium stores and the nitric oxide/cGMP pathways). This report highlights some of these similarities and distinctions in the hope that it will encourage scientific discourse and research activity in this area, eventually leading to an improved quality of life for those millions of individuals that are afflicted with bladder and erectile dysfunction.

Animals↗

PubMed2000

Disease surveillance and data collection issues in epidemic modelling.

This paper is founded on a tutorial session given to the School on Modern Statistical Methods in Medical Research which was held at the International Centre for Theoretical Physics, Trieste in September 1999. We review the aims, scope and purposes of infectious disease surveillance including determining transmission information to underpin model structure and parameterization in epidemic modelling. The practical problems inherent in collecting surveillance data are illustrated by a study of HIV/AIDS in Cambodia. We also review the basic elements of mathematical models developed to represent the transmission dynamics of infectious diseases, and discuss reasons for the gap between mathematical epidemic models and available data.

Cambodia↗

PubMed2006

Service user involvement in nursing, midwifery and health visiting research: a review of evidence and practice.

OBJECTIVES: In the UK policy recommends that service users (patients, carers and the public) should be involved in all publicly funded health and social care research. However, little is known about which approaches work best in different research contexts and why. The purpose of this paper is to explain some of the theoretical limitations to current understandings of service user involvement and to provide some suggestions for theory and methods development. This paper draws upon findings from a review of the research 'evidence' and current practice on service user involvement in the design and undertaking of nursing, midwifery and health visiting research. DESIGN: A multi-method review was commissioned by the NHS Service Delivery and Organisation (SDO) Research and Development Programme. The timeframe was April 2004-March 2005. The full report (Ref: SDO/69/2003) and supplementary bibliography are available from: http://www.sdo.lshtm.ac.uk. REVIEW METHODS/DATA: Initial searches of the health and social care literature and consultations with researchers were used to develop a broad definition of the topic area. A service user reference group (26 members) worked with the project team to refine the scope of the review, to set inclusion criteria and develop a framework for the analysis. Systematic searches of the literature were undertaken online and through library stacks (345 relevant documents were identified). Ongoing and recently completed studies that had involved service users were identified through online databases (34 studies) and through a national consultation exercise (17 studies). Selected studies were followed up using telephone interviews (n=11). Members of the service user reference group worked with the research team to advise on key messages for dissemination to different audiences. RESULTS: Information was gained about contextual factors, drivers, concepts, approaches and outcomes of service user involvement in nursing, midwifery and health visiting research, as well as developments in other research fields. Synthesis of this information shows that there are different purposes and domains for user involvement, either as part of researcher-led or user-led research, or as part of a partnership approach. A number of issues were identified as being important for future research. These include: linking different reasons for service user involvement with different outcomes; understanding the relationship between research data and service user involvement, and developing conceptualisations of user involvement that are capable of accommodating complex research relationships. Suggestions for the development of practice include: consideration of diversity, communication, ethical issues, working relationships, finances, education and training. CONCLUSIONS: Because research is undertaken for different reasons and in different contexts, it is not possible to say that involving service users will, or should, always be undertaken in the same way to achieve the same benefits. At a research project level uniqueness of purpose is a defining characteristic and strength of service user involvement.

Community Health Nursing↗

PubMed1985

A critical review of the literature on acrolein toxicity.

A detailed literature review of human and animal toxicity studies of acrolein is presented, and information gaps identified that call for further investigation. Specific recommendations are suggested for additional short-/long-term studies, including chemical disposition and cytogenetic investigations. Two bibliographies are provided indicating the scope of the review: (1) literature actually cited and (2) literature examined but not included.

Acrolein↗