Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Therapy development”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources

[Atrial fibrillation in Wolff-Parkinson-White syndrome. Development and therapy].

In patients with Wolff-Parkinson-White syndrome the accessory pathway may participate in various tachyarrhythmias thereby influencing symptoms and prognosis. Atrial fibrillation occurs in 10 to 32% of patients and may have life-threatening consequences by precipitating ventricular fibrillation in patients with rapid conduction due to an accessory pathway with short anterograde refractory period (< 250 ms). Pathogenesis of atrial fibrillation in the WPW syndrome and therapeutic options are reviewed in this presentation. Spontaneous degeneration of atrioventricular reentrant tachycardia has been reported to represent the most frequent mode of initiation of atrial fibrillation during electrophysiologic study (up to 64% of episodes). Hemodynamic changes during tachycardia may lead to increased sympathetic tone, hypoxemia or increased tension of the atrial wall, thus, triggering atrial fibrillation. Induction of reentrant tachycardia during electrophysiologic study also has shown to be strongly correlated to its clinical prevalence and is inducible in up to 77% of patients with atrial fibrillation. The pathogenesis and high incidence of atrial fibrillation in patients with WPW syndrome is related to presence and functional properties of the accessory pathway. After surgical excision or catheter ablation more than 90% of patients are free of this arrhythmia. Anterograde conduction properties of the pathway appear to be more important than retrograde properties. High incidence of atrial fibrillation is related to short anterograde refractory periods, and of note, this arrhythmia is rare (3%) in patients with concealed pathways. With intracardiac recordings, Jackman et al. could demonstrate atrial fibrillation due to micro-reentry originating in accessory pathway networks.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Fibrillation↗

Comparison of the efficacy and cost effectiveness of pre-emptive therapy as directed by CMV antigenemia and prophylaxis with ganciclovir in lung transplant recipients.

BACKGROUND: CMV disease remains a major complication of lung transplantation and attempts to prevent it have met with marginal success. In a previous study we documented that universal prophylaxis did not prevent CMV disease but merely delayed it, and was very costly. METHODS: We compared the efficacy and cost of pre-emptive therapy with ganciclovir, guided by CMV antigenemia, to that of historic controls that received universal prophylaxis with ganciclovir. CMV antigenemia assay was done routinely and pre-emptive therapy was initiated if greater than 25 CMV positive cells per 100,000 polymorphonuclear cells were found. RESULTS: Nineteen patients were enrolled; 6 of of whom received 12 courses of pre-emptive therapy. The incidence of CMV disease was 26% compared to 38% for the historical controls (p = 0.51). None of the patients that received pre-emptive therapy developed CMV disease following that therapy. Antigenemia failed to predict disease in 5 patients that developed it, and thus it is unknown if pre-emptive therapy could have prevented it. There was no mortality in either the study patients or historic controls directly related to CMV. The net savings with pre-emptive therapy was $2569 per patient. CONCLUSIONS: We conclude that pre-emptive therapy with ganciclovir is as safe and effective as universal prophylaxis in preventing CMV disease in lung transplant recipients, and is less expensive. The appropriate surveillance technique and timing remain to be determine to optimize the efficacy of pre-emptive therapy.

Adult↗

Recommendations for clinical trial evaluation of acute stroke therapies.

The development of therapies for acute ischemic stroke has achieved a few notable successes and, unfortunately, many unsuccessful efforts. Many valuable lessons for the future assessment of new acute stroke therapies can be gleaned from the positive and negative prior trials. Phase I and II trials must be carefully designed and implemented to derive relevant, valuable information needed to proceed to phase III trials with promising interventions. The phase III trial should evaluate drug efficacy in an appropriately targeted stroke population evaluated by a meaningful and reliable outcome measure. Combinations of various types of stroke therapies will likely be increasingly assessed in future trials that are designed and implemented by cooperative efforts between the pharmaceutical industry, government agencies, academic advisors and clinical investigators. The chances for future success in demonstrating efficacy with acute stroke therapies will be enhanced by carefully conceived, scientifically based clinical trials. The recommendations contained in this document may help to focus attention on how to achieve the goal of developing an expanding number of a effective and safe acute stroke therapies.

Acute Disease↗

The assessment of psychophysiological dysfunction in children using the BSE scale before and during therapy.

The purpose of exchange and development therapies (EDT) is to reduce the behavioural problems which are the expression of psychophysiological dysfunction. The aim of this study was to reveal the most disturbed psychophysiological functions and their evolution during the course of EDT in 42 children divided into three groups; group I--15 children with pure autism (A); group II--16 children with autism associated with neurological disorders (AA); and group III--11 children with pervasive developmental disorders (PDD). Among the 12 functions analysed, groups AA, A and APDD had respectively 8, 6 and 4 functions in which the score was high (> 2.5), indicating serious disorders (maximum 4). All the dysfunctions improved during EDT. However, each group had certain areas which were more susceptible to treatment. Further analysis of behaviour problems led to a more precise definition of the objectives and to the adaptation of the therapeutic methods to obtain greater effectiveness.

Adolescent↗

Photodynamic therapy of malignant tumors--recent developments.

Photodynamic therapy (PDT) is a promising new cancer treatment modality in which tumor cells are killed as a result of photoactivation of a tumor-localizing photosensitizing agent. Since activating light can be targeted specifically to tumors, and tumor-selective photosensitizing agents are being developed, this treatment has the potential to induce highly selective destruction of malignant cells. To date, PDT has been applied to a large variety of human carcinomas, resulting in successful eradication of single tumor nodules and several types of superficial tumors. Current research is aimed at improving the efficacy and tumor-selectivity and tumor destruction. The most immediate benefits of PDT are likely to be seen in patients treated with a combination of this and other forms of therapy.

Animals↗

Essential tremor.

Essential tremor (ET) is one of the most common neurological diseases; although it is a disease about which we are only beginning to develop an understanding. Effective treatment options for the disorder are severely limited. The traditional view of ET as a benign, familial, monosymptomatic disorder is being replaced by one of ET as a disease or family of diseases with aetiological, clinical, and pathological heterogeneity. Recent identification of putative environmental toxins linked to ET provide hope for disease prevention through a reduction in exposure to risk factors. Pathological and genetic studies will yield new insights into disease pathogenesis and mechanisms, which may result in the development of more effective symptomatic therapies developed with an understanding of the disease biology. These insights also have the potential to form the basis for neuroprotective therapies.

Essential Tremor↗

Heparin-induced thrombocytopenia.

OBJECTIVE: To highlight the importance of heparin-induced thrombocytopenia (HIT), a potentially fatal adverse effect of heparin therapy. CASE SUMMARY: There are two types of HIT with distinct etiology. Type 1 HIT is a relatively mild thrombocytopenia of early onset that generally resolves with ongoing heparin therapy. Clinical complications are uncommon. Type 2 HIT, which is more severe, is the main focus of this report. Five patients receiving heparin therapy developed type 2 HIT, which in some cases resulted in complications that required limb amputation, or eventuated in death. DISCUSSION: In a patient receiving heparin therapy, the development of thrombocytopenia should alert the caregiver to the possible development of HIT. Prompt management of HIT can help prevent complications. HIT usually manifests 5-8 days after starting heparin therapy. The platelet count usually decreases to less than 100 x 10(3)/mm3. It generally normalizes within 5-7 days after discontinuing heparin therapy. In spite of the thrombocytopenia, thrombosis or disseminated intravascular coagulation can occur. The management may be subdivided into three clinical situations: mild-to-moderate asymptomatic thrombocytopenia, severe thrombocytopenia with a platelet count of less than 50 x 10(3)/mm3, and thrombosis or embolism complicating HIT. CONCLUSIONS: Heparin-induced thrombocytopenia is an uncommon but potentially serious, and sometimes lethal, complication of heparin therapy. Therefore, it is important to be aware of the possibility of the development of HIT with heparin therapy, to recognize it early, and to manage it appropriately before the manifestation of adverse effects.

Adult↗

Leukocyte-endothelial interactions: clinical trials of anti-adhesion therapy.

OBJECTIVE: This review describes efforts to develop therapies directed at leukocyte and endothelial adhesion molecules for the treatment of acute and chronic inflammatory diseases, including hemorrhagic shock. DATA SOURCES AND STUDY SELECTION: Published research and review articles and Web sites relating to the clinical use of drugs directed to leukocyte or endothelial cell adhesion molecules. DATA EXTRACTION AND SYNTHESIS: The results of relevant studies of adhesion blockade are reviewed. Trials in putative clinical ischemia-reperfusion disorders, particularly traumatic shock, are emphasized. Trials are designated as positive or negative, depending on whether the primary end points established by the trial investigators were met. CONCLUSIONS: Blockade of leukocyte adhesion to endothelium by monoclonal antibodies or other antagonists has been demonstrated to reduce vascular and tissue injury in a wide variety of animal models of inflammatory and immune disease. Anti-adhesion therapy directed at lymphocyte trafficking has shown efficacy in several phase 2 and 3 clinical trials in inflammatory bowel disease, multiple sclerosis, and psoriasis. Despite strong preclinical data, results of phase 2 and 3 trials of neutrophil adhesion blockade in putative ischemia-reperfusion disorders-stroke, myocardial infarction, and hemorrhagic shock-have been disappointing.

Cell Adhesion Molecules↗

International developments in behavior therapy in Latin America.

The development of behaviour therapy in Latin America is presented, beginning with the work of Keller and Bijou in Brazil and Mexico respectively. In the decade of the 70's the experimental analysis of behaviour and interventions to change undesired behavior were considered scientific and professional alternatives to psychoanalysis. Psychologists trained in objective methodology began work on clinical problems, and were followed by psychiatrists not satisfied with traditional approaches. Today behavior therapy and behavior modifications are known and practiced in the majority of the Latin American countries. Important basic research is in progress.

Behavior Therapy↗

Advanced breast cancer: recent developments in hormonal therapy.

OBJECTIVES: To review recent developments in hormonal therapy for metastatic breast cancer. DATA SOURCES: Published books and articles. CONCLUSIONS: Newer hormonal agents are offering women alternatives for sequential therapy of metastatic disease that provide benefit with less risk. IMPLICATIONS FOR NURSING PRACTICE: A thorough understanding of the relationship between hormonal influences and breast cancer will assist nurses to better appreciate the variety of agents now available and their specific indications, outcomes, and effects. Common side effects include weight gain, hot flashes, nausea, and skin and vaginal changes. Nursing efforts focus on the areas of body image disturbance, side effect management, and fostering healthy relationships.

Aromatase Inhibitors↗

Vitreoretinal findings similar to retinopathy of prematurity in infants with compound heterozygous protein S deficiency.

OBJECTIVE: To present previously undescribed vitreoretinal findings similar to severe retinopathy of prematurity (ROP) in two siblings (daughter and son) with a thrombophilic disorder, compound heterozygous protein S (PS) deficiency. DESIGN: Family genotype study and literature review. PARTICIPANTS: Two unrelated heterozygous PS-deficient parents and their two children with compound heterozygous PS deficiency were studied. The gestational age and birth weight of the daughter were 40 weeks and 3200 g, respectively, and those of the son were 34 weeks and 2150 g, respectively. Three other neonates with homozygous or compound heterozygous PS deficiency and ophthalmologic findings were identified in the literature. INTERVENTION: The daughter underwent lensectomy-vitrectomy at 48 weeks adjusted age bilaterally. The son underwent therapy developed for severe ROP: laser therapy of the peripheral avascular retina at 39 weeks adjusted age, and bilateral lensectomy-vitrectomy with membrane peel of intravitreous proliferation from the optic disc at 42 weeks adjusted age. MAIN OUTCOME MEASURES: The main clinical outcome measures were retinal appearance and functional vision. Genotypes of the family members were determined. RESULTS: One of the four eyes retained functional vision. A normal-appearing posterior retina, normal scotopic and photopic flash electroretinograms, and a normal flash visual-evoked response were documented from the left eye of the son at 62 weeks adjusted age. The other three eyes had inoperable retinal detachments and no functional vision. The mother had type I PS deficiency and the father had type II PS deficiency. Compound heterozygous PS deficiency was confirmed in both children. CONCLUSION: In both children, normal vasculogenesis was interrupted. At 39 weeks adjusted age, the retinal examination of the son revealed extraretinal fibrovascular proliferation at the optic disc (reactivation of the hyaloid system) and in the peripheral retina (interruption of inner retinal vascularization). Patients with homozygous or compound heterozygous PS deficiency may present as infants with severe ROP. The authors' experience suggests that appropriately timed surgical procedures, which are efficacious for ROP, can preserve vision in infants with thrombophilic disorders.

Adult↗

Percutaneous tumor ablation: increased necrosis with combined radio-frequency ablation and intravenous liposomal doxorubicin in a rat breast tumor model.

PURPOSE: To determine whether a combination of intravenous liposomal doxorubicin and radio-frequency (RF) ablation increases tumor destruction compared with RF alone in an animal tumor model. MATERIALS AND METHODS: R3230 mammary adenocarcinoma 1.4-1.8-cm- diameter nodules were implanted subcutaneously in 132 female Fischer rats. Initially, tumors were treated with (a) conventional, monopolar RF (mean, 250 mA +/- 25 [SD] at 70 degrees C +/- 1 for 5 minutes) ablation alone, (b) RF ablation followed by intravenous administration of 1 mg of liposomal doxorubicin, (c) RF ablation followed by intravenous administration of 1 mg of empty liposomes, (d) RF ablation and direct intratumoral administration of liposomal doxorubicin, or (e) no treatment. Subsequently, the dose (0.06-2.00 mg) of liposomal doxorubicin, the timing of administration (3 days before to 3 days after RF ablation), and the time of pathologic examination (0-72 hours after treatment) were varied. RESULTS: Mean coagulation diameter for treated tumors follows: 6.7 mm +/- 0.6, RF ablation alone; 11.1 mm +/- 1.5, RF ablation and intravenous administration of empty liposomes (P <.05, compared with RF ablation alone); and 8.4 mm +/- 1.1, RF ablation with intratumoral administration of liposomal doxorubicin (P <.05, compared with RF ablation alone). Maximal increased mean coagulation diameter (13.1 mm +/- 1.5) was observed with a combination of liposomal doxorubicin and RF ablation (P <.001, for all comparisons). The increased coagulation for combination therapy developed over 48 hours after therapy. Coagulation diameter did not vary with the doxorubicin concentration range and was not dependent on the timing of administration of liposomal doxorubicin from 3 days before to 24 hours after RF ablation. CONCLUSION: Intravenous administration of liposomal doxorubicin can improve RF ablation, since it increases coagulation diameter in solid tumors compared with RF ablation alone or a combination of RF ablation with administration of empty liposomes.

Animals↗

Underutilization of isoniazid chemoprophylaxis in tuberculosis contacts 50 years of age and older. A prospective analysis.

STUDY OBJECTIVES: To examine the utilization of chemoprophylaxis for tuberculosis in certain high-risk groups, ie, infected contacts 50 years and older, and to study the safety of isoniazid (INH) preventive therapy in such persons. DESIGN: From 1987 to 1992, two-part questionnaires were sent to each of the regional health offices within the 95 counties of Tennessee to document cases of purified protein derivative skin test conversion or reaction among close contacts of new patients with active tuberculosis. Infected contacts 50 years and older were included in the study. METHODS: Data collected from these questionnaires were grouped according to age, sex, race, liver functions test (LFT), and whether chemotherapy was completed. Reasons for early discontinuation were also recorded. High values of LFTs were classified in the various groups as either twofold elevation or greater than threefold elevation. RESULTS: Of the 829 responses for persons fitting the criteria for INH chemoprophylaxis, 415 began treatment; 249 (60%) of those completed the full course (9 months) and 166 stopped prematurely. Of the 414 persons (50%) who did not start preventive therapy, 233 (56.5%) respondents listed age as the reason. No patients started on a regimen of therapy developed hepatitis. Of those completing therapy, 6.9% had a rise in liver enzyme values but remained asymptomatic for hepatitis. Liver enzyme level elevation was significantly higher among patients who discontinued therapy, particularly white women, than those who completed the full course. Asymptomatic liver enzyme level elevation (> or = 3 times normal value), private practitioners' preferences, and patients arbitrarily stopping therapy were the leading reasons for incomplete INH preventive therapy. CONCLUSION: We conclude that 30% of tuberculosis-infected contacts deserving chemoprophylaxis were actually provided the full benefit of INH preventive therapy, indicating underutilization of this prevention strategy, particularly in contacts older than 50 years.

Age Distribution↗

The role of the music therapist on the hospice/palliative care team.

Music therapists make significant contributions to the multidisciplinary hospice team in its efforts to provide holistic palliative care to terminally ill patients and family members and to promote quality of life. The role of a hospice music therapist is described, including providing direct patient music therapy service, training the hospice team in music therapy, developing and maintaining a music therapy resource centre, and offering bereavement services. A review of patient charts provides information about patient age, sex, diagnosis, and source and reasons for referral.

Bereavement↗

Adaptive hypersensitivity to estrogen: mechanism for sequential responses to hormonal therapy in breast cancer.

Clinical observations demonstrate that women with breast cancer often respond to subsequent endocrine manipulation after resistance to initial hormonal therapy develops. As a mechanistic explanation for these findings, we hypothesized that human breast tumors can adapt in response to the pressure exerted by endocrine therapy with development of hypersensitivity to estradiol. To understand the signaling pathways responsible, we examined estrogenic stimulation of cell proliferation in a model system and provided in vitro and in vivo evidence that long-term deprivation of estradiol (LTED) causes adaptive hypersensitivity. Even though the estrogen receptor alpha (ERalpha) is markedly up-regulated in LTED cells, the enhanced responses to estradiol do not appear to involve mechanisms acting at the level of transcription of estrogen-regulated genes. We found that ERalpha co-opts a classical growth factor pathway and induces rapid nongenomic effects that are enhanced in LTED cells. Estradiol binds to cell membrane-associated ERs, physically associates with the adaptor protein Shc, and induces its phosphorylation. In turn, Shc binds Grb2 and Sos, which result in the rapid activation of mitogen-activated protein kinase. These nongenomic effects of estradiol produced biological effects, as evidenced by Elk-1 activation and by morphological changes in cell membranes. The mechanistic pathways involved in adaptive hypersensitivity suggest that inhibitors of the mitogen-activated protein kinase and phosphatidylinositol-3-OH kinase pathways might prevent the development of adaptive hypersensitivity and allow more prolonged efficacy of endocrine therapies.

Adaptor Proteins, Signal Transducing↗

Positive employment service - facilitating employment for people living with HIV.

As treatments and therapies develop and improve, enhancing life expectancy, Human Immunodeficiency Virus (HIV) has been described by some as a long term chronic condition rather than an acute life threatening illness. As this change occurs, new issues become relevant for the person living with HIV, employment being one of these. In light of this, the Positive Employment Service was developed and implemented to explore and address some of the issues related to employment for people living with HIV. The original concept for the service was primarily focused on vocational rehabilitation; however, it soon became clear that there was a need for a prevocational service facilitating transition and adjustment to productivity roles. The service was developed using approaches from Vocational and Occupational Therapy Models of Practice. This article discusses the challenges of developing and implementing this service and explores the unique perspective that occupational therapy brings to a position of this kind.

Journal Article↗

Gastro-intestinal side effects of clofazimine.

Three out of 30 patients of leprosy getting clofazimine therapy developed severe gastrointestinal side effects following the therapy in the dose of 100 mg after one month, eight months and five weeks respectively. One of the patients died due to the side effects. Indian patients appear to be more prone to severe gastrointestinal side effects of clofazimine and may develop the same after shorter duration of therapy with smaller doses of the drug.

Adult↗