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PubMed2004

Genomic and proteomic technologies for individualisation and improvement of cancer treatment.

The development of microarray-based technologies for characterising tumours, both at the genomic and proteomic levels, has had a significant impact on the field of oncology. Gene expression profiling of various human tumour tissues has led to the identification of expression patterns related to disease outcome and drug resistance, as well as to the discovery of new therapeutic targets and insights into disease pathogenesis. Protein microarray technologies, such as reverse-phase protein arrays, provide the unique opportunity to profile tissues and assess the activity of signalling pathways within isolated cell populations. This technology can be used to identify patients likely to benefit from specific treatment modalities and also to monitor therapeutic response in samples obtained during and after treatment. Routine application of genomic and proteomic microarray technologies in clinical practice will require significant efforts to standardise the techniques, controls and reference standards, and analytical tools used. Extensive, independent validation using large, statistically-powered datasets will also be necessary. Inclusion of concomitant genomic and proteomic-based molecular profiling techniques into clinical trial protocols will bring us closer to the reality of patient-tailored therapy.

Gene Expression Profiling↗
PubMedDate not supplied

Treatment decision-making by men with localized prostate cancer: the influence of personal factors.

OBJECTIVES: For many men with localized prostate cancer, there is no definite answer or unequivocal choice regarding treatment modality. This high-stakes treatment decision is made in the context of great uncertainty. The purpose of this study is to systematically document meaningful and relevant aspects of treatment decision-making reported by men with localized prostate cancer. METHODS: Focus groups and individual interviews were conducted with 44 men who were within 6 months of a diagnosis of localized prostate cancer. Using content analysis and grounded theory analytic techniques, major aspects and processes of men's treatment decision making are identified and described. RESULTS: The participants reported their experiences beginning with influential personal history factors, followed by detailed descriptions of information gathering and the important influence of expected treatment outcomes and other individuals' cancer histories and/or shared opinions. Twenty of the 44 (45%) participants relied heavily on the influence of another's opinion or history to finalize a decision, yet only 10 of the 44 (22.7%) reported this individual to be their physician. A common process, "making the best choice for me" was explicated. CONCLUSION: Clinicians assume that men are making rational treatment decisions based on reliable information, yet this study documents a different reality. Patient education about medical therapies and the patients' own medical factors is not enough. A clinic visit dialogue that brings personal factors to the conversation along with medical factors can guide a man to making his "best choice" for localized prostate cancer.

Aged↗
PubMed1995

The human face of elderly care?

Communication and interactions between nurses and patients with dementia of the Alzheimers type is often inadequate. It would be inappropriate to suggest that nursing staff make no effort to communicate with patients who have dementia, but the communication difficulties that confront them require that a conscious effort is made to invest extra energy to provide meaningful communication. A number of interactive approaches are used by staff, traditionally those of reality orientation, behaviour modification, reminiscence therapy, and more recently, music therapy, touch therapy and aromatherapy. This paper overviews one other therapy which specifically addresses the communication needs of patients who suffer from dementia of the Alzheimers type, validation therapy.

Aged↗
PubMed1985

The fetal neural tube: is intervention progress?

Fetal therapy has now become a reality and many centres specializing in this field have been established in several countries. The in utero treatment of fetal hydrocephalus is bedevilled by many problems, including poor patient selection, problems with shunt design and general lack of understanding of the pathogenesis of hydrocephalus. Implantation of a ventriculo-amniotic shunt employing a one-way valve into the fetal skull allows continuous evacuation of CSF. One such model has been developed by us and should be ready for clinical trials in the near future. There is strong evidence that the fetal brain has a high capacity for rapid growth and regeneration. However, the process is poorly understood and there is great need for further study. No attempts have yet been made to treat spina bifida in utero. However, the advantages demonstrated in our earlier studies using allogeneic bone transplantation in utero resulted in the development of an allogenic bone paste. This substance can be moulded to any desired shape and is ideal for the restoration of bone loss resulting from cranial injuries or the correction of skull defects. The allogeneic bone paste has been also applied in utero for the repair of surgically induced spina bifida-like lesions in the animal model.

Animals↗
PubMed1993

Thymidine kinase mutants obtained by random sequence selection.

Knowledge of the catalytic properties and structural information regarding the amino acid residues that comprise the active site of an enzyme allows one, in principle, to use site-specific mutagenesis to construct genes that encode enzymes with altered functions. However, such information about most enzymes is not known and the effects of specific amino acid substitutions are not generally predictable. An alternative approach is to substitute random nucleotides for key codons in a gene and to use genetic selection to identify new and interesting enzyme variants. We describe here the construction, selection, and characterization of herpes simplex virus type 1 thymidine kinase mutants either with different catalytic properties or with enhanced thermostability. From a library containing 2 x 10(6) plasmid-encoded herpes thymidine kinase genes, each with a different nucleotide sequence at the putative nucleoside binding site, we obtained 1540 active mutants. Using this library and one previously constructed, we identified by secondary selection Escherichia coli harboring thymidine kinase mutant clones that were unable to grow in the presence of concentrations of 3'-azido-3'-deoxythymidine (AZT) that permits colony formation by E. coli harboring the wild-type plasmid. Two of the mutant enzymes exhibited a reduced Km for AZT, one of which displayed a higher catalytic efficiency for AZT over thymidine relative to that of the wild type. We also identified one mutant with enhanced thermostability. These mutants may have clinical potential as the promise of gene therapy is increasingly becoming a reality.

Amino Acid Sequence↗
PubMed2002

Fetal hematopoietic stem cell transplantation: a challenge for the twenty-first century.

Successful in utero hematopoietic stem cell transplantation will likely represent a major step forward in the management of patients with congenital hematological, metabolic, and immunological disorders. We review the naturally occurring models of hematopoietic chimerism in animals and humans, as well as available experimental animal data and human clinical attempts of fetal transplantation. Data available from naturally occurring models and experimental models of fetal transplantation suggest that this technique should be translatable to the human fetus. However, to date, the success of human fetal hematopoietic stem cell therapy has been limited to fetuses with severe immunologic defects. Evaluation of successful attempts of human transplantation, the ontogeny of fetal immune development, and data available from animals provide insights into innovative approaches to fetal therapy that may bring the reality of successful fetal transplantation closer.

Animals↗
PubMed2002

Differentiation of monkey embryonic stem cells into neural lineages.

Embryonic stem (ES) cells are self-renewing, pluripotent, and capable of differentiating into all of the cell types found in the adult body. Therefore, they have the potential to replace degenerated or damaged cells, including those in the central nervous system. For ES cell-based therapy to become a clinical reality, translational research involving nonhuman primates is essential. Here, we report monkey ES cell differentiation into embryoid bodies (EBs), neural progenitor cells (NPCs), and committed neural phenotypes. The ES cells were aggregated in hanging drops to form EBs. The EBs were then plated onto adhesive surfaces in a serum-free medium to form NPCs and expanded in serum-free medium containing fibroblast growth factor (FGF)-2 before neural differentiation was induced. Cells were characterized at each step by immunocytochemistry for the presence of specific markers. The majority of cells in complex/cystic EBs expressed antigens (alpha-fetal protein, cardiac troponin I, and vimentin) representative of all three embryonic germ layers. Greater than 70% of the expanded cell populations expressed antigenic markers (nestin and musashi1) for NPCs. After removal of FGF-2, approximately 70% of the NPCs differentiated into neuronal phenotypes expressing either microtubule-associated protein-2C (MAP2C) or neuronal nuclear antigen (NeuN), and approximately 28% differentiated into glial cell types expressing glial fibrillary acidic protein. Small populations of MAP2C/NeuN-positive cells also expressed tyrosine hydroxylase (approximately 4%) or choline acetyltransferase (approximately 13%). These results suggest that monkey ES cells spontaneously differentiate into cells of all three germ layers, can be induced and maintained as NPCs, and can be further differentiated into committed neural lineages, including putative neurons and glial cells.

Animals↗
PubMedDate not supplied

Comparative evaluation of alpha-galactosidase A infusions for treatment of Fabry disease.

Enzyme therapy has proven safe and effective in preventing and reversing many manifestations in patients with Gaucher disease. On the basis of this success, enzyme therapy is now becoming a reality for Fabry disease, alpha-galactosidase A deficiency. Two products, agalsidase alpha and beta, have been tested in pivotal trials. The substantial differences between the study structures and outcome measures have made direct comparisons difficult. Here, the strengths and weaknesses of these trials are compared: achievement of stated endpoints, safety and, potential efficacy. In addition, the need for additional long-term data is emphasized because this is not attainable in short-term trials for a chronic disease.

Animals↗
PubMed2001

Classification of chronic venous insufficiency: a review.

Chronic venous insufficiency (CVI) is a very variable and complex entity that has stimulated different attempts at classification. Several proposals have been made in recent years, based on objective and anatomical criteria, most of them incomplete and unsatisfactory. Finally the CEAP classification was presented in 1994. This certainly is the most nearly complete classification, since it takes into consideration not only the main aspects of CVI: Clinical, Etiological, Anatomical, and Pathophysiological, but also the degrees of severity, reported in the form of scores. It is now accepted internationally although it still has some flaws (such as the absence of the corona phlebectactica sign) and inaccuracies (above all in the clinical part and the scoring). Recently, some members of the Promoting Committee proposed a substantial modification of the part on scores, coming closest to the clinical reality, instrumental diagnosis, and current therapies. The characteristics of CEAP enable us to affirm that this represents the most original and useful classification, not only for clinical studies, but also in the assessment of therapeutic results and in patient follow-up. Like all classifications, CEAP also needs to be validated by means of clinical studies in order to demonstrate its applicability. For this purpose, a European Working Group was set up in 1997. The first interesting results of 872 dossiers collected by means of a computerized program (European Phlebological File) were presented at several international congresses and concentrated on the consistency and reproducibility of the clinical part of the CEAP classification in different clinical settings.

Chronic Disease↗
PubMed2002

[Theories emerging from daily clinical practice of community occupational therapists].

Occupational therapists working in the community have adapted their knowledge to the distinct characteristics and expectations of the various settings. To do so, they have had to reflect on the professional nature of their interventions, while intervening. This simultaneous process has yielded specific knowledge that is solidly anchored in current clinical reality. A survey on occupational therapy in the Centres locaux de services communautaires in Québec (CLSC) highlighted three theories developed by occupational therapists in their daily clinical practice. The first relates mostly to referral processing while the other two address the occupational therapist's role within the treatment team. This paper briefly presents the survey's results, then focuses mainly on the three emergent theories and underlines some elements congruent with the reference theories in occupational therapy. The author then proposes avenues for reflection to help foster balance between the constraints inherent to the community health care system and occupational therapy professional values.

Community Health Services↗
PubMed2001

[Children with cancer--great progress, a lot of good news and some disappointments].

Each year, between 125 and 150 children under the age of 15 develop cancer in Norway. More than half of the children are less than five years of age at diagnosis. The malignancy is often of an embryonal origin and the disease spectrum very different from that in adults. Our progress in understanding and treating childhood malignancies is one of the success stories in paediatrics and in cancer biology and management. In the Nordic countries, about three of four children with cancer are cured, but the progress is different in different disease groups. For some malignancies, survival is close to 100%, while progress for other types have been much slower. However, cancer is still the main cause of death in children above one year of age who die of a disease. The progress has its price. The treatment is often intensive, with great morbidity and a definite mortality. Late effects are also of great concern. A more specific therapy targeted against the malignant cell, with less damage to normal cells, has long been our goal. Progress in recent years in the understanding of the malignant cells has now given the first definite examples that such targeted therapy may soon become a reality.

Adolescent↗
PubMed2001

Targeted gene correction strategies.

We are now approaching the reality of success in gene therapy as our knowledge of the genetic basis of disease continues to grow, coupled with improved delivery methods for therapeutic nucleic acid molecules. It is apparent that gene therapy can be divided into two specific and very different approaches in which gene replacement, or augmentation, is differentiated from gene repair. In fact, gene augmentation is characterized by the delivery of the coding sequence of the gene of interest in an expression cassette. In contrast, gene repair differs in that the process targets for correction of the mutation responsible for the genetic disorder. The in situ repair of a gene has many advantages over conventional replacement methods. This review will concentrate on the various strategies currently available for gene repair. The potential benefits of correction versus augmentation will be addressed and possible future developments outlined.

Cells, Cultured↗
PubMed2002

[Changes in the epidemiology of infectious diseases in Chile from 1990 to 2000].

In the last decade in Chile, there was a large reduction in the rate of communicable diseases, especially typhoid fever, and those preventable through the universal vaccination programs. Exceptions were hepatitis A and Pertussis. The reduction in tuberculosis, has lead the country to a threshold in which the elimination of tuberculosis as a public health problem is reachable. The HIV epidemic is still expanding, at higher rate among women and heterosexual men, keeping drug addiction as a low ranked risk factor. At the end of the century, universal or expanded access to HIV therapy was still not a reality. Cholera was a well controlled emerging infection, but Hantavirus infection has become a major threat in many regions. Syphilis and especially gonorrhea have decreased, but condyloma has increased dramatically. The nosocomial infection scenario has changed somehow, due to more severely ice and complex patients admitted to hospitals. Multiresistant nosocomial pathogens continue expanding (S aureus, fermentor and non fermentor gram negative rods, especially A baumannii). The country has been able to expand control programs to almost all hospitals. Antimicrobial resistance has continued growing. The massive and indiscriminate use of antibiotics, largely responsible for the resistance, grew worse until the sale of antimicrobials in pharmacies was restricted by law. This had a major impact, with important reduction in sales of most, but not all, antibiotics. The impact in resistance rate of this reduction, if any, has yet to be assessed.

Chile↗
PubMed1994

Small bowel transplantation.

After struggling for three decades, SBT is finally emerging as a clinical reality. To become the standard therapy for the treatment of end-stage intestinal failure, SBT must offer a better quality of life, fewer risks, and lower costs than home TPN. To achieve this standard, protocols must be refined to obtain lower rates of rejection and infection as well as more consistent graft function.

Clinical Protocols↗
PubMed1993

Pain and the placebo response.

The placebo response is a powerful widespread phenomenon which relieves many conditions including pain. It depends on the patient's belief or expectation that the therapy is effective. It is an unpopular topic because it is confused with quackery or seen as an expensive artifact or taken to challenge the rationale of a therapy or to mock the reality of the senses. In order to avoid taking the subject seriously, myths are invented claiming that placebos work only on hysterics or hallucinators or that they are the equivalent of doing nothing or that they act only on the mental results of pain and not on the pain itself. These myths are dismissed. A model of the brain is presented in which preconscious decisions are made as to appropriate behaviour. Pain is perceived only after a decision has been made that it is appropriate to the biological needs of the individual.

Animals↗
PubMed2005

Airway gene therapy and cystic fibrosis.

Airway disease in cystic fibrosis (CF) is the major cause of death and is presently inadequately treatable, but genetic therapies offer the hope that such life-long disease will be curable, or at least satisfactorily treated. Normal pathogen defences that have evolved on airway surfaces also prevent the various gene vectors now available from producing effective gene transfer. Nevertheless, findings from basic research and human clinical trials are revealing how these barriers might be overcome or circumvented, with benefits to therapeutic efficacy and patient safety. Though progress is slower than expected or desired, the therapeutic rewards will be great when safe and effective gene therapy for CF airway disease becomes a clinical reality.

Airway Obstruction↗
PubMed1979

Reality orientation and staff attention: a controlled study.

A trial was carried out of Reality Orientation (R.O.) in a residential home for the elderly mentally infirm with a 'social therapy' control group, receiving the same amount of staff attention as the R.O. group, in addition to an untreated control group. R.O. residents improved more on tests of information and orientation and various aspects of memory than controls. These results support the hypothesis that the nature of staff attention is crucial and that it should encourage and reward appropriate behaviour. No differential effects of treatment were found on rating scale assessments of the resident's functioning in the home.

Aged↗
PubMed1976

Behavioral change in the chronicity pattern of dementia in the institutional geriatric resident.

To determine whether behavioral change as a result of environmental stimulation can be reported in individualized terms for the aged with organic brain syndrome or senile dementia, a program of multimodal group interactive therapy was started in an extended care facility. During a 1.5-year period, the study included 108 residents, whose average age was 84 years. The technique used was a combination of modified Reality Orientation, Remotivation, Activity and Milieu therapies. Thirteen groups residing in different wings of the facility were treated for 55 sessions by 11 activity specialists and 2 elderly volunteers under the supervision of the consulting clinical psychologist. Data were collected on emerging behavioral changes with respect to awareness, attention, verbalized ideation, voice quality, speech quantity, sociability, self-care, quality of affect, energy level, expressed somatic concern and physical movement. Of the initial 108 residents, 80 had chronic brain syndrome of varying severity or senile dementia. During treatment, 35 of these 80 residents (44 percent) were improved, 17 (20 percent) were unchanged, 14 (18 percent) became worse, and 14 (18 percent) remained unrated. The results warrant a redifinition of the psychotherapeutic approach. It should include factors other than the severity and chronicity of disease in determining the prognosis for behavioral change in geriatric institutional residents.

Behavior↗