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At least 145 records · Page 8Linked to original sources

Establishment of an immortalized human hepatic stellate cell line to develop antifibrotic therapies.

Because human hepatic stellate cells (HSCs) perform a crucial role in the progress of hepatic fibrosis, it is of great value to establish an immortalized human cell line that exhibits HSC characteristics and grows well in tissue cultures for the development of antifibrotic therapies. Thus, we engineered an immortalized human hepatic stellate cell (HSC) line TWNT-4 by retrovirally inducing human telomerase reverse transcriptase (hTERT) into LI 90 cells established from a human liver mesenchymal tumor. Parental LI 90 entered replicative senescence, whereas TWNT-4 showed telomerase activity and proliferated for more than population doubling level (PDL) 200 without any crisis. TWNT-4 expressed platelet-derived growth factor-beta receptor (PDGF-betaR), alpha-smooth muscle actin (alpha-SMA), and type I collagen (alpha1) and was considered to be an activated form of HSCs. Treatment of TWNT-4 cells with either 100 U/ml of IFN-gamma or 1 ng/ml of rapamycin (Rapa) for 14 days led to lower expression of type I collagen (alpha1) at RNA and protein levels. Exposure of TWNT-4 cells to both of IFN-gamma (10 U/ml) and Rapa (0.1 ng/ml) for 14 days effectively decreased the expression of type I collagen (alpha1), PDGF-betaR, and alpha-SMA expression and suppressed TGF-beta1 secretion of TWNT-4 cells. We successfully induced apoptosis by transducing TNF-related apoptosis-inducing ligand (TRAIL) into TWNT-4 cells using adenovirus vectors Ad/GT-TRAIL and Ad/PGK-GV-17. These findings suggested that immortalized activated HSC line TWNT-4 would be a useful means to develop antifibrotic therapies.

Actins↗

The community intensive therapy team: development and philosophy of a new service.

The Community Intensive Therapy Team (CITT) has been operating since 1998. It was developed to cater for the needs of patients with complex difficulties referred to a specialist Child and Adolescent Health Service (CAMHS) in South Wales, UK. The patients served by the CITT are comparable with patients who might be referred for admission to an inpatient unit and include patients with eating disorders, psychosis, affective disorders, adjustment disorders or repetitive self-harm. The theoretical model used is based on a biopsychosocial model which aims to empower and support family members. The philosophy of the CITT is to work with the child and family in their own environment, tailoring the therapy to the needs of all concerned. CITT makes use of the strengths within the patient, the family and extended family, the agencies already involved and the environment. Since its introduction, the CITT has been able to manage all the complex referrals made to it from the generic Tier 2/3 CAMHS teams it serves, with minimal recourse to inpatient beds.

Adolescent↗

A new machine for continuous renal replacement therapy: from development to clinical testing.

A new continuous renal replacement therapy machine has been designed to fulfill the expectations of nephrologists and intensivists operating in the common ground of critical care nephrology. The new equipment is called Prismaflex and it is the natural evolution of the PRISMA machine that has been utilized worldwide for continuous renal replacement therapy in the last 10 years. The authors performed a preliminary alpha-trial to establish the usability, flexibility and reliability of the new device. Accuracy was also tested by recording various operational parameters during different intermittent and continuous renal replacement modalities during 62 treatments. This article will describe our first experience with this new device and touch upon the historic and technologic background leading to its development.

Clinical Trials as Topic↗

Effect of oestrogen replacement therapy on development of experimental arteriosclerosis: a study in transplanted and balloon-injured rabbit aortas.

The mechanism underlying possible protection of oestrogen replacement therapy against cardiovascular disease appears to go beyond beneficial changes in plasma lipoproteins. A direct action of oestrogen on the metabolism of lipoproteins after entering the arterial wall may occur. The present study evaluated whether oestrogen replacement therapy affects the development of experimental arteriosclerosis in immunologically injured (experiment A + B) and balloon-injured (experiment B) aortas in ovariectomized rabbits maintained at a human level of plasma cholesterol; both models involve severe damage to the endothelium with resulting rapid accumulation of lipoproteins in the arterial intima and therefore appear suitable for studying factors directly affecting subendothelial lipoprotein metabolism. In experiment A, dietary cholesterol required to maintain a human level of plasma cholesterol was significantly higher for the oestrogen group than for the placebo group. Similarly, cholesterol accumulation in the aortic grafts was borderline higher for the oestrogen than the placebo group, whilst intimal hyperplasia was without difference between the groups. Due to a modified schedule of cholesterol feeding in experiment B, oestrogen and placebo groups received the same amount of dietary cholesterol, and cholesterol accumulation and intimal hyperplasia were similar in immunologically injured and balloon-injured parts of the aorta in both groups. These results suggest that in the female rabbit maintained at a human level of plasma cholesterol, oestrogen replacement therapy has no direct action on the development of experimental arteriosclerosis when induced by immunological or mechanical injury to the endothelium.

Animals↗

A comparison of microcomputer-aided and traditional language therapy for developing communication skills in nonoral toddlers.

This investigation looked at the vocabulary learning and use, and social and communication growth of 8 severely handicapped toddlers under two different language conditions. A computer-based approach was compared to traditional intervention techniques. Treatment conditions were administered in randomized order by two graduate student clinicians. Communication growth was assessed by using a standard set of measures administered before the intervention, at midpoint between the two treatment conditions, and at the end. The results from this study indicated that the subjects made notable progress regardless of the treatment condition received.

Child↗

Sarcoidosis developing during therapy for breast cancer.

Two women with breast carcinoma developed bilateral hilar adenopathy, with pulmonary infiltrate in one, during treatment for breast carcinoma. There was strong suspicion of metastatic disease from breast carcinoma. However, biopsy of a mediastinal node in first patient and transbronchial specimen biopsy in the second patient proved the diagnosis to be sarcoidosis. In one patient improvement was noted without therapy, and in the other improvement was noted with steroid treatment.

Adult↗

Developments in therapy for extensive-disease small cell lung cancer.

Developments in the treatment of extensive small cell lung cancer have proven effective in palliative management but have not yielded improvements in the cure rate for this disease. Strategies involving dose escalation of chemotherapy, including de novo and late intensification dose escalation and dose escalation with growth factor support, have had mixed results in this patient population. Alternating chemotherapy, especially with regimens containing etoposide, has achieved better results overall but has not had a significant impact on survival. Current treatment goals should therefore be focused on short-term palliation of symptoms, at least until more effective drugs are developed. Exploration of resistance modulation strategies and biologic approaches, as well as determining the true value of protracted etoposide treatment, may play a role in future treatment endeavors.

Antineoplastic Combined Chemotherapy Protocols↗

[Association between UVA1 and PUVA bath therapy and development of malignant melanoma].

After 18 months of intensive UVA1- and bath PUVA therapy for urticaria pigmentosa, a female patient developed a malignant melanoma on the right thigh. This can be taken as further indication that intense UVA1 or PUVA therapy is capable of inducing malignant melanoma, even though this risk has not been completely proven. The total dose of UVA1 was 910 J/cm2, while the total dose of PUVA was 214.4 J/cm2. It is unclear to what extent modified UVA application of long-wave UVA light (UVA1) and modified PUVA therapy (bath PUVA) have a similar risk compared to known data.

Adult↗

Virtues and pitfalls of EAE for the development of therapies for multiple sclerosis.

Experimental autoimmune encephalomyelitis (EAE) is a useful model for aiding the development of new treatments for MS. All therapies approved for MS ameliorate EAE. Two approved medications, glatiramer acetate and Natalizumab, were developed directly from studies in EAE. Several trials are ongoing in MS after success in EAE, including altered peptide ligands of myelin, DNA vaccines and statins. However, EAE has failed to predict the outcome of certain approaches. The reasons underlying such failures are discussed here.

Animals↗

Molecular therapy in a model neuroendocrine disease: developing clinical gene therapy for pituitary tumours.

The main objectives of pituitary tumour treatment are to restore normal function of the pituitary gland and prevent tumour recurrences. In spite of the success of current therapies in the treatment of relatively small tumours, new therapeutic alternatives need to be explored for large invasive tumours, tumour recurrences postsurgery, and when intolerance to drug treatment develops. Gene therapy, which uses nucleic acids as drugs, is a very attractive alternative to classic therapeutic modalities. With the development of efficient gene delivery vectors, which allow widespread distribution and long-term transgene expression with limited side effects, the clinical implementation of gene therapy for the treatment of pituitary tumours will become a reality within the next five to ten years.

Adenoviridae↗

Electroporation gene therapy: new developments in vivo and in vitro.

Electroporation-based gene therapy has become a "hot field" for non-viral gene delivery. This review summarizes the progress made in intramuscular and intratumoral electrogenetransfer, which include new applications and modifications. The progress in dendritic cell (DC) and stem cell transfection by use of electroporation has also been discussed. Rapid progress during the past two years clearly demonstrates the great potential of this technology, but there are challenges faced by both in vitro and in vivo applications, which include how to enhance the transfection efficiency for intratumoral delivery, how to extend the duration of gene expression for intramuscular injection, and how to increase the survival rate for in vitro cell transfection. Resolving these issues will shed new light on this field.

DNA, Recombinant↗

Behavioral observation of children during play therapy: preliminary development of a research instrument.

There is a need for a measure of children's playroom behavior to assess areas of functioning relevant to diagnosis, therapy process, and outcome, as discussed in clinical literature. This study concerned the development of a Play Therapy Observational Instrument designed to meet criteria specified as necessary for such a measure. Two nonclinicians were trained in the observation and scoring of 31 child behaviors. The observations were made on video tapes and transcripts of ongoing play therapy sessions. Results indicated that 13 of the behaviors were scored with a high level of interjudge reliability. These reliable scores formed three statistically valid and theoretically meaningful subscales: emotional discomfort, use of fantasy play as a coping method, and the quality of the child's interaction with the therapist. Children's scale scores were sufficiently stable within sessions and across two therapy sessions to indicate that they reflected individual differences. Relationships between scales were assessed and discussed in the light of theoretical controversies. Implications for future research were discussed.

Adaptation, Psychological↗

Problems and prospects of developing effective therapy for common cold viruses.

No effective treatment for common colds has yet been developed. Combination antiviral and anti-inflammatory therapies are the best hope for intervention after the onset of symptoms. Prophylaxis, especially in the form of vaccination, would have a major impact in disease prevention. These approaches offer new avenues for treating populations at risk and are of particular significance to those with asthma or chronic bronchitis.

Adrenal Cortex Hormones↗

Chemoradiation therapy: effect on dental development.

Chemoradiation therapy used on pediatric oncology patients often causes dental developmental anomalies that affect future dental care. Defects noted include tooth and root agenesis, root thinning and shortening, and localized enamel defects. Histologically, these defects appear as osteoid-like niches in the developing dentin which alter the overlying enamel. Odontogenic cell sensitivity is dependent upon the position on the cell cycle and the mitotic activity at the time of chemoradiation therapy. Knowledge of the stage of dental development at the time of oncology treatment and the type of therapy allows the clinician to predict dental effects of the chemoradiation. Representative cases illustrate the clinical manifestations of chemoradiation on the developing dentition.

Ameloblasts↗

Developing guidelines for thrombolytic therapy.

The development and implementation of guidelines for the use of thrombolytic therapy at a 1000-bed community hospital are described. A thrombolytic therapy committee composed of two physicians, a nurse, and a pharmacist was established to develop the guidelines. The committee outlined goals for the guidelines, developed a format, and defined individual responsibilities. Indications, absolute requirements for use, contraindications, administration procedures, necessary tests before and during infusion, and recommendations for the use of anticoagulant therapy following thrombolytic therapy were listed. All of the committee members participated in educating the hospital staff involved with thrombolytic therapy. The pharmacist served as a liaison with the laboratory and used a flow sheet to monitor all patients receiving thrombolytic therapy. Two years after the guidelines were implemented an evaluation of physician compliance and adverse effects secondary to thrombolytic therapy showed excellent compliance (97-100% on all criteria listed) and an incidence of bleeding comparable with the values reported in the literature for heparin. The guidelines are reviewed annually by the committee and revised when necessary. The use of thrombolytic guidelines has minimized adverse effects and the misuse of laboratory tests, assisted with proper patient selection, and united several disciplines in a collaborative fashion toward a common goal.

Connecticut↗

[Future developments in the therapy of acute ST segment elevation myocardial infarction].

The treatment and therapy of acute myocardial infarction has substantially improved during the past decades. After thrombotic coronary occlusion had been identified as the underlying cause of myocardial infarction, thrombolysis emerged as the standard therapy. The development of more and more effective thrombolytic therapies and optimization of adjunctive antithrombotic therapies resulted in improved clinical outcomes and decreased mortality rates of acute myocardial infarction patients. Optimization of percutaneous coronary intervention (PCI) techniques including implantation of coronary stents shifted the therapeutic approach from thrombolysis toward acute mechanical reperfusion. The safety and efficacy profile of PCI has been made possible by the development of potent antiplatelet agents such as clopidogrel and glycoprotein (GP) IIb/IIIa antagonists. For the future therapy of acute myocardial infarction the following goals will be important to consider: (1) are there ways to increase the percentage of patients reaching out for medical support when suffering from acute myocardial infarction?, (2) what strategies will be useful to shorten coronary reperfusion time?, (3) are there means to protect affected myocardium from ischemic damage?, and (4) can necrotic myocardium be reconstituted functionally? Potential approaches such as improved public information, combination of thrombolytic and interventional therapy to accelerate coronary reperfusion, pharmacological protection of myocardium by modulation of myocardial metabolism or protection from reperfusion damage as well as progenitor cell therapy are discussed in this overview.

Angioplasty, Balloon, Coronary↗