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At least 685 records · Page 38Linked to original sources
PubMed1995

Construction of retroviral vectors for targeted delivery and expression of therapeutic genes.

Current gene therapy protocols take an ex vivo approach in which cells are removed from a patient, genetically modified and then reimplanted. However this kind of approach is both cumbersome and costly, requiring high tech facilities and is limited to cell types that can be easily cultured. The in vivo delivery of genes by retroviral vectors will greatly facilitate gene therapy protocols of the future. However before in vivo gene therapy becomes a reality a number of problems must be overcome. Ideally therapeutic genes should be delivered only to the relevant cell type and/or expressed in this cell type. Strategies are described that (I) limit therapeutic gene delivery, using pseudotyping or vectors based on retroviruses that show a restricted infection spectrum or (II) limit the expression of transferred genes by inclusion of tissue specific promoters or cis acting regulatory elements. The combination of some of these strategies should permit the construction of novel retroviral vectors that provide safe and targeted in vivo gene transfer.

Animals↗
PubMed1996

Prenatal diagnosis of beta-thalassaemia and sickle cell anaemia in Turkey.

This paper reports our experience of molecular analysis and diagnosis of beta-thalassaemia and sickle cell anaemia (HbS) in 70 prospective parents of Turkish descent and their fetuses. Molecular screening was carried out by allele-specific oligonucleotide (ASO) hybridization of amplified DNA to the 12 most common mutations in the Turkish population. By using this approach, we were able to define the mutation in 95 per cent of chromosomes investigated. Genomic sequencing led to the additional detection of three rare mutations: Cd 44 (-C), IVS-I-5 (G-C), and IVS-I-116 (T-G). All diagnoses were successfully accomplished and no misdiagnosis occurred. Consanguineous marriage appears to contribute significantly to the frequency of affected births in Turkey. Out of the 14 homozygous fetuses, six were the result of close consanguinity. This study indicates that fetal diagnosis of beta-thalassaemia and HbS may be obtained in practically all cases, even in a heterogeneous population like the Turkish population, when early methods of fetal sampling are combined with polymerase chain reaction (PCR)-based techniques. Until gene therapy becomes a reality, the only approaches to the control of haemoglobinopathies are prevention and avoidance. The most relevant and common aspects of the programmes, which have been very effective in reducing the birth rate of beta-thalassaemia major in several at-risk areas of the Mediterranean basin, are the continuous educational campaigns directed at the population at large, the voluntary basis, and non-directive counselling. The most important challenge for the eradication of the haemoglobinopathies in Turkey is the organization of a nation-wide and comprehensive genetic preventive programme based on DNA technology.

Anemia, Sickle Cell↗
PubMed2001

Myocardial gene transfer.

Recent improvements in both gene transfer vectors and in vivo gene delivery techniques have facilitated genetic manipulation of myocardial function and enabled targeted therapy of animal models of cardiac disease and, in particular, heart failure. Increases in myocardial perfusion, improved calcium handling, and enhanced beta-adrenergic receptor signaling have all been achieved by gene transfer in animal models, and appear to be important determinants of myocardial function. Increased understanding of the molecular etiologies of myocardial disease processes combined with advances in vectors and gene delivery will facilitate the development of novel therapies and represent important progress in the effort to make myocardial gene therapy a clinical reality beyond experimental protocols.

Animals↗
PubMed2002

Virtual reality in the treatment of spider phobia: a controlled study.

This study explored whether virtual reality (VR) exposure therapy was effective in the treatment of spider phobia. We compared a treatment condition vs. a waiting list condition in a between group design with 23 participants. Participants in the VR treatment group received an average of four one-hour exposure therapy sessions. VR exposure was effective in treating spider phobia compared to a control condition as measured with a Fear of Spiders questionnaire, a Behavioural Avoidance Test (BAT), and severity ratings made by the clinician and an independent assessor. Eighty-three percent of patients in the VR treatment group showed clinically significant improvement compared with 0% in the waiting list group, and no patients dropped out. This study shows that VR exposure can be effective in the treatment of phobias.

Adolescent↗
PubMed1998

Sphincter preservation in rectal cancer. External-beam radiation therapy alone.

Surgery with or without adjuvant radiation therapy and chemotherapy is the standard treatment for patients with resectable rectal carcinoma. Many patients, however, are medically unfit or simply refuse surgery that could result in a colostomy. This article reviews the results of external-beam radiation therapy alone for selected patients with rectal carcinoma and its role in preserving anorectal function. For patients with mobile tumors, a 5-year survival and local relapse-free rate of 30% and 25%, respectively, can be expected after external-beam radiation therapy alone, and 60% remain colostomy free. Results of radiation therapy alone in patients with fixed or unresectable tumors are poor. Although more than a third of patients remain colostomy-free, only 5% of patients survive 5 years. In patients with mobile rectal carcinomas that are not amenable to sphincter-preserving surgery, who are unfit medically for radical surgery, or who refuse a colostomy, external-beam radiation therapy offers the reality of sphincter preservation and the possibility of long-term tumor control.

Anal Canal↗
PubMed2004

Modeling the cancer patient with genetically engineered mice: prediction of toxicity from molecule-targeted therapies.

Current trends foretell the use of cancer treatments customized to each patient. Genetic and molecular profiling of tumors and an increasing number of molecule-targeted therapies contribute to making this a reality. However, as targets of anticancer therapies become specific proteins or pathways, unanticipated side effects may emerge. In addition, the chronic use of these treatments may contribute to the development of degenerative toxicity not predicted by short-term clinical trials. Here we review and propose how genetically engineered mouse models can serve as valuable tools to predict targeted therapy toxicity, as well as to identify allelic variants that predispose individuals to side effects.

Animals↗
PubMed2003

Vascular access and patient outcomes in hemodialysis: questions answered in recent literature.

Hemodialysis is not possible without access to the vascular system to provide an adequate and reliable source of blood flow through the hemodialyzer. Since maintenance hemodialysis therapy became a reality in the latter half of the twentieth century, no vascular access has exceeded the success and reliability of arteriovenous fistulae (AVF). They have the lowest infection and thrombosis rates, have the longest patency rates, and are associated with the best morbidity and mortality outcomes of any access modality. In the United States, the majority of patients starting hemodialysis do not have a primary AVF, which may explain why vascular access complications represent almost 20% of the total spending for hemodialysis. In addition, as much as 50% of hospitalization costs for end-stage renal disease are related to access issues. Every effort must be directed in the U.S. as well as elsewhere to promote the use of AVF whenever possible. In some European countries, more than 90% of patients have AVF as their hemodialysis access when nephrologists perform placement of vascular access. Already, some programs in the U.S. have recognized the need for trained nephrologists to provide these services. U.S. interventional nephrologists should be given the opportunity to learn AVF placement procedures to emulate their European counterparts, and thus improve U.S. dialysis outcomes.

Arteriovenous Shunt, Surgical↗
PubMedDate not supplied

Current treatment for Alzheimer disease and future prospects.

A cascade of pathophysiological events is triggered in Alzheimer disease (AD) that ultimately involves common cellular signaling pathways and leads to cellular and network dysfunction, failure of neurotransmission, cell death, and a common clinical outcome. The process is asynchronous, meaning that viable neurons remain as targets for therapy even in the diseased state, and each stage of the cascade affords the possibility for therapeutic intervention. Cholinesterase inhibitors are the only available treatment in the United States for patients with mild to moderate AD, helping maintain cognitive and functional abilities in most patients and conferring beneficial behavioral effects in some. Memantine is an NMDA receptor antagonist that has recently been approved in Europe for treatment of moderately severe to severe AD and is under investigation in the United States. Its mechanism of action may include enhanced neurotransmission in several systems as well as antiexcitotoxic effects. There are data regarding the effectiveness of the combination of memantine with cholinesterase inhibitors that will be useful for the practicing clinician. Other agents have shown some benefit in clinical trials, including the antioxidants vitamin E, selegiline, and Ginkgo biloba extracts, although the weight of evidence regarding their effects is not sufficient to define clinical practice. Potential future therapies currently are in development that target multiple aspects of the illness cascade, including aberrant inflammation, neurotrophic function, and processing of beta amyloid and tau proteins. These newer approaches hold promise for disease modification but are as yet unproven. Whether or not disease-modifying or preventive therapies become a reality, clinicians will be faced with AD patients who require treatment at all stages of illness for the indefinite future. Cholinergic and emerging noncholinergic medications will likely prevail as the standards of treatment for years to come.

Alzheimer Disease↗
PubMed1988

Experimental study to evaluate nursing staff morale in a high stimulation geriatric psychiatry setting.

This work is part of a larger study carried out at Murray Royal Hospital, Perth, Scotland. The study was concerned with staff morale under two distinct management approaches towards the care of the elderly patient with dementia. In one ward a dynamic, high stimulation approach was adopted including reality orientation, reminiscence therapy and socialization therapy. This was run in a well-structured manner by the ward staff and other agents. The other ward had no such structure imposed and was left to carry out 'traditional' nursing care to a high standard. The tool used to collect the data was a precoded questionnaire developed by Jones & Galliard. The hypothesis on which the study was based was as follows, 'that morale is increased in nursing staff involved in a high stimulation ward environment for the hospitalized elderly patient with dementia'. The findings of the study appear to indicate that the hypothesis is supported. It appears that the imposition of the structured high stimulation management approach was responsible for such an outcome and that nursing staff respond well to such an approach.

Aged↗
PubMed2007

Regulating MHC expression for cellular therapeutics.

BACKGROUND: In the past decade, regenerative medicine and cell-based therapies have emerged as new science and technology, with the main goal of repairing, replacing, or regenerating new tissues. A critical issue in this field is the high polymorphism of HLA, which compromises immune acceptance. The lentivirus-mediated delivery of short-hairpin RNAs (shRNAs) has proved to be an efficient method to inhibit the translation of a specific gene. STUDY DESIGN AND METHODS: A lentiviral-based vector system was used for drug-inducible expression of shRNA sequences that target either beta2-microglobulin (beta2m) or HLA heavy-chain transcripts. RESULTS: The transduction of inducible RNA interference cassettes containing the sequences for shRNAs targeting beta2m or HLA heavy chain suppressed HLA class I expression by up to 90 percent in HeLa and B-lymphocyte cell lines as well as in peripheral blood monocytes. The expression of HLA class I antigens was fully restored in these cells after the drug had been discontinued. It was demonstrated that HLA class I knockdown was effective in preventing antibody-mediated cell lysis and CD8+ T-cell response. The residual HLA expression in HLA-silenced cells may provide sufficient protection against natural killer cell-mediated lysis. CONCLUSIONS: These data demonstrate the feasibility of controlling HLA expression by genetically modifying cell-based therapeutics to overcome the limitations of immune rejection, bringing cellular therapies closer to reality.

CD8-Positive T-Lymphocytes↗
PubMed1979

The creative arts therapies as "real therapies".

Elements of a standard definition of psychotherapy are used to support the argument that the creative arts therapies should not be characterized as adjunctive therapies, or discredited as not being "real therapies." Two concepts widely acknowledged as important in the application of the creative arts therapies are discussed: first, that the nonverbal media employed by creative arts therapists tap emotional rather than cognitive processes and evoke responses more directly and immediately than traditional verbal therapies, and, second, that creative arts therapies are reality-based and provide a more immediate and real link to a patient's experience than something he can portray only verbally.

Attitude of Health Personnel↗
PubMed1976

Trends in the development of reconstruction tomography in neuroradiology.

Because of the new uses of CT, it is difficult to accurately forecast the future balance between it and conventional radiologic techniques. However, the relatively low frequency resolution of CT makes it unlikely that conventional radiology will be completely replaced. Photon noise and the iodine concentration of the contrast medium limit the size of the cerebral vessels which can be studied by CT. Thus angiography is likely to remain the method of choice for fine-detail study of these vessels. For optimal measurements and comparative studies, improved head fixation is required. Given precisely reporducible positioning, stereotaxic surgery and radiation therapy become a reality.

Computers↗
PubMed2000

Preclinical (premotor) Parkinson's disease.

Parkinson's disease (PD) is an idiopathic disease caused by necrosis and apoptosis of dopaminergic cells in the brainstem, which are probably induced by oxidative stress. Current therapeutic strategies comprise symptomatic and restorative treatment. Neuroprotective treatment, however, is close to becoming reality. As neuroprotective therapy may be of particular benefit to the preclinical and/or very early PD patients, identifying patients in the early stages of the disease is a priority. Both [18F]dopa positron emission tomography (PET) and [123I]beta-CIT single photon emission computed tomography (SPECT) imaging may be useful tools in diagnosing early (preclinical) PD. As screening the whole population for preclinical PD is not realistic, one has to select subjects with a high risk for this disease. Olfactory disturbances, subtle neurocognitive dysfunction, visuomotor control abnormalities and, to a lesser degree, mood and personality disorders, have lately been suggested to precede or accompany early clinical motor hallmarks of PD. In an epidemiological study, 500 first-degree relatives of PD patients were assessed for these signs and symptoms, and [123I]beta-CIT SPECT was performed on patients in the top 10% and the bottom 10% with regard to sense of smell. In this report, the study design and initial data from this ongoing study will be presented.

Humans↗
PubMed2001

The use of bisphosphonates in children with osteogenesis imperfecta.

Children with osteogenesis imperfecta (OI) suffer recurrent fractures resulting in pain, deformity and disability. There is no accepted medical therapy for the condition other than symptomatic pain relief, and surgical correction of the deformities. Recent experience with the bisphosphonate group of drugs suggests, however, that anti-resorptive therapy may reduce fracture frequency, increase bone density, promote remodeling of previously crush-fractured vertebrae, reduce chronic pain, and improve mobility in both children and infants. The prospects for preventing disability and deformity, and perhaps improving growth in affected children are good. Current studies are focusing on the evaluation of the efficacy of oral drug therapy, and protocols are under development to evaluate new, more efficient molecules. Until gene therapy becomes a reality, the use of bisphosphonates appears to be the most efficient way of altering the natural course of severe OI, and improving the quality of life of patients.

Diphosphonates↗
PubMed2000

Preliminary findings from the National Pre-ESRD Education Initiative.

Regardless of age or race, more patients preferred peritoneal dialysis (PD) than would be expected from the current ratio of patients treated with PD in the U.S. The percent of patients choosing PD seems to be largely influenced by the scope of information they receive prior to therapy initiation. In the absence of thorough treatment option education, a significant number of patients may be assigned a therapy when, in reality, they would have selected an alternative option. There is a need to further understand the correlation between a practice's PD utilization rate and the extent to which patients are given dialysis treatment options.

Adult↗
PubMed2003

Good news and bad news: the cost of mending a broken heart.

The approval of a new treatment protocol known as "destination therapy" highlights the realities of today's health economics. This article discusses the technology, the economics and the philosophy of the newly approved left-ventricular-assist systems.

Cost-Benefit Analysis↗
PubMed2006

Return to work for individuals with Human Immunodeficiency Virus (HIV) disease: dichotomous outcome variable or personally-constructed narrative challenge?

Advances in the management of HIV disease have increasingly focused attention on the possibilities of return to employment for individuals with HIV disease. However whilst mortality has decreased and life expectancies have lengthened, life for the individual with HIV remains both complex and unpredictable. This article explores the notion of return to work as narrative theme. A case study highlighting the narrative nature of how return to work might be conceptualised by the HIV positive individual is presented; ahead of a brief discussion as to how the lived reality of combination therapy may impact upon the individual's conceptualisation of employment in the broader context of their life story.

Adult↗