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PubMed1975

Correlation of plasma propranolol concentration with therapeutic response in patients with angina pectoris.

The therapeutic response to propranolol was evaluated in patients with documented coronary artery disease at doses varying from 40 to 320 mg/day. Therapeutic response was quantified by evaluating exercise performance on a treadmill and then related to plasma propranolol concentration. Plasma propranolol was defined in terms of beta-adrenergic blockade by comparison with dose (concentration) response curves in normal subjects. Individual therapeutic benefit occurred at doses which averaged 144 +/- 21 mg/day and at concentrations which averaged 30 +/- 7 ng/ml. There was a wide variation between both dose and concentration among the patients at maximum therapeutic response, but when the plasma propranolol was related to pharmacologic activity, the maximum therapeutic response was observed between 64 to 98% of total blockade. Despite the increased exercise performance in these patients, the double product of heart rate and systolic blood pressure was always less, suggesting either an alteration of the relation between myocardial oxygen consumption and the double product during propranolol or a reduction on oxygen delivery to the myocardium as the result of beta-adrenergic blockade of the coronary vasculature.

Administration, Oral↗
PubMed2005

Therapeutic potential of endothelial progenitor cells in cardiovascular diseases.

Endothelial dysfunction and cell loss are prominent features in cardiovascular disease. Endothelial progenitor cells (EPCs) originating from the bone marrow play a significant role in neovascularization of ischemic tissues and in re-endothelialization of injured blood vessels. Several studies have shown the therapeutic potential of EPC transplantation in rescue of tissue ischemia and in repair of blood vessels and bioengineering of prosthetic grafts. Recent small-scale trials have provided preliminary evidence of feasibility, safety, and efficacy in patients with myocardial and critical limb ischemia. However, several studies have shown that age and cardiovascular disease risk factors reduce the availability of circulating EPCs (CEPCs) and impair their function to varying degrees. In addition, the relative scarcity of CEPCs limits the ability to expand these cells in sufficient numbers for some therapeutic applications. Priority must be given to the development of strategies to enhance the number and improve the function of CEPCs. Furthermore, alternative sources of EPC such as chord blood need to be explored. Strategies for improvement of cell adhesion, survival, and prevention of cell senescence are also essential to ensure therapeutic viability. Genetic engineering of EPCs may be a useful approach to developing these cells into efficient therapeutic tools. In the clinical arena there is pressing need to standardize the protocols for isolation, culture, and therapeutic application of EPC. Large-scale multi-center randomized trials are required to evaluate the long-term safety and efficacy of EPC therapy. Despite these hurdles, the outlook for EPC-based therapy for cardiovascular disease is promising.

Aging↗
PubMed2002

Diffusion MRI: a new strategy for assessment of cancer therapeutic efficacy.

The use of anatomical imaging in clinical oncology practice traditionally relies on comparison of patient scans acquired before and following completion of therapeutic intervention. Therapeutic success is typically determined from inspection of gross anatomical images to assess changes in tumor size. Imaging could provide significant additional insight into therapeutic impact if a specific parameter or combination of parameters could be identified which reflect tissue changes at the cellular or physiologic level. This would provide an early indicator or treatment response/outcome in an individual patient before completion of therapy. Moreover, response of a tumor to therapeutic intervention may be heterogeneous. The use of imaging could assist in delineating therapeutic-induced spatial heterogeneity within a tumor mass by providing information related to specific regions that are resistant or responsive to treatment. Largely untapped potential resides in exploratory methods such as diffusion MRI, which is a nonvolumetric intravoxel measure of tumor response based upon water molecular mobility. Alterations in water mobility reflect changes in tissue structure at the cellular level. While the clinical utility of diffusion MRI for oncologic practice is still under active investigation, this overview on the use of diffusion MRI for the evaluation of brain tumors will serve to introduce how this approach may be applied in the future for the management of patients with solid tumors.

Brain Neoplasms↗
PubMed1990

Enhancing the impact of therapeutic interventions.

A therapeutic intervention has impact if it reaches the patient's mind and remains available for times of need. Impact is the overcoming of attention, neglect and forgetfulness. Therapists enhance impact by: (a) building up patients' positive attention; (b) creating unusual and discrepant events; (c) strengthening the therapeutic message or the way it is conveyed; (d) drawing out patients' readiness for commitment and hard work; (e) creating bridges between therapy and the problem situation; (f) protecting the therapeutic message from trivializing and levelling events. These principles are nonspecific and are here illustrated by examples from widely different therapeutic approaches. Impact is not a substitute for the inherent value of a therapeutic message, but its lack can doom even our greatest inspirations.

Adaptation, Psychological↗
PubMed1998

Changes in seizure threshold over the course of electroconvulsive therapy affect therapeutic response and are detected by ictal EEG ratings.

Therapeutic effectiveness of electroconvulsive therapy is influenced by the degree to which the stimulus intensity exceeds the seizure threshold. However, the threshold rises variably over the treatment course, confounding maintenance of desired relative stimulus intensity. In 47 depressed patients, decreases in relative stimulus intensity between treatments 1 and 6 were associated with diminished therapeutic response at treatment 6 for unilateral (UL) ECT. A multivariate model including manual ratings of ictal EEG data predicted whether seizure threshold rose with 82% accuracy. The same EEG variables were also significantly related to therapeutic response. Thus, decreases in relative stimulus intensity over the ECT course affect the therapeutic potency of UL ECT. Further, ictal EEG indices have considerable potential for predicting such stimulus intensity changes and their effect on therapeutic outcome.

Aged↗
PubMed1998

Outcomes of homeless mentally ill chemical abusers in community residences and a therapeutic community.

OBJECTIVES: The feasibility and effectiveness of treating homeless mentally ill chemical abusers in community residences compared with a therapeutic community were evaluated. METHODS: A total of 694 homeless mentally ill chemical abusers were randomly referred to two community residences or a therapeutic community. All programs were enhanced to treat persons with dual diagnoses. Subjects' attrition, substance use, and psychopathology were measured at two, six, and 12 months. RESULTS: Forty-two percent of the 694 referred subjects were admitted to their assigned program and showed up for treatment, and 13 percent completed 12 months or more. Clients retained at both types of program showed reductions in substance use and psychopathology, but reductions were greater at the therapeutic community. Compared with subjects in the community residences, those in the therapeutic community were more likely to be drug free, as measured by urine analysis and self-reports, and showed greater improvement in psychiatric symptoms, as measured by the Center for Epidemiological Studies--Depression Scale and the Brief Psychiatric Rating Scale. Their functioning also improved, as measured by the Global Assessment of Functioning scale. CONCLUSIONS: Homeless mentally ill chemical abusers who are retained in community-based residential programs, especially in therapeutic communities, can be successfully treated.

Adult↗
PubMed1985

Therapeutic drug monitoring--the need for audit?

The experience of therapeutic drug monitoring (TDM) of seven drugs as part of the normal biochemistry services over the period April 1982-83 is reported. Reagent costs alone for these assays exceeded pounds 15,000. Of 1,841 digoxin estimations, 56 per cent fell within the therapeutic range whereas 25 per cent were potentially toxic. Fifty per cent of 968 lithium measurements were lower than 4 mg L-1, placing many of these patients at risk of treatment failure. Only 29 per cent and 32 per cent of 369 theophylline and 440 phenytoin concentrations respectively were within their well-established ranges. In only around 20 per cent of requests for theophylline and phenytoin assay was sufficient clinical information supplied to the laboratory. In the majority of patients with theophylline or phenytoin concentrations outwith the therapeutic range, further analysis was not requested and so optimisation of dosage cannot be assumed to have occurred. The wide therapeutic ranges of carbamazepine and phenobarbitone ensured that most patients attained acceptable concentrations. Sodium valproate analysis was requested on 160 occasions despite the poor correlation between the concentration of this drug and its therapeutic and toxic effects. TDM can be an expensive exercise which must be subjected to rigorous cost-benefit analysis. Requests should be made on a customised drug assay form and interpretative advice on individual patient problems made available. Recommendations for the organisation, daily running and clinical supervision of TDM are made.

Anti-Arrhythmia Agents↗
PubMed2006

A trial of therapeutic hypothermia via endovascular approach in awake patients with acute ischemic stroke: methodology.

BACKGROUND: Therapeutic hypothermia has been shown to be of benefit in improving neurological outcome in cardiac arrest. It now is being investigated in acute stroke and myocardial infarction. The majority of the literature describes its use in intubated, pharmacologically paralyzed patients, using surface cooling techniques that are susceptible to patient shivering, imprecise temperature control, time lag to target-temperature acquisition, and rebound hyperthermia. OBJECTIVES: To develop a method of inducing therapeutic hypothermia in a rapid, precise, and tolerable fashion in awake, nonintubated patients. METHODS: This method was developed for an ongoing clinical trial investigating a combination of therapeutic hypothermia and intravenous thrombolysis for acute ischemic stroke. In the protocol, an endovascular cooling device is placed in the inferior vena cava of a patient, and a combination of buspirone, meperidine, and cutaneous warming with a heating blanket is used to suppress shivering as the patient is cooled to a target temperature of 33 degrees C, kept there for a total of 24 hours from hypothermia initiation, and then rewarmed in a controlled fashion during the next 12 hours. RESULTS: Ten patients underwent the therapeutic hypothermia protocol. The median pretreatment core temperature was 36.1 degrees C (interquartile range [IQR]: 35.8 degrees C-36.4 degrees C). On initiation of cooling, the core temperatures dropped rapidly and then leveled off, approaching a median plateau value of 33.4 degrees C (IQR: 33.2 degrees C-33.9 degrees C) in a mean time of 1.7 (+/- 0.7) hours from cooling initiation, with a median average postplateau temperature during the cooling phase of 33.8 degrees C (IQR: 33.3 degrees C-34.6 degrees C), and a median lowest temperature of 33.1 degrees C (IQR: 33.0 degrees C-33.3 degrees C). The procedure was well tolerated, with minimal shivering and no rebound hyperthermia. CONCLUSIONS: This is a method by which a rapid and precise therapeutic decrease in core temperature can be achieved without the necessity for intubation or neuromuscular blockade and with minimal patient discomfort or shivering.

Adolescent↗
PubMed2005

DNA-based therapeutics and DNA delivery systems: a comprehensive review.

The past several years have witnessed the evolution of gene medicine from an experimental technology into a viable strategy for developing therapeutics for a wide range of human disorders. Numerous prototype DNA-based biopharmaceuticals can now control disease progression by induction and/or inhibition of genes. These potent therapeutics include plasmids containing transgenes, oligonucleotides, aptamers, ribozymes, DNAzymes, and small interfering RNAs. Although only 2 DNA-based pharmaceuticals (an antisense oligonucleotide formulation, Vitravene, (USA, 1998), and an adenoviral gene therapy treatment, Gendicine (China, 2003), have received approval from regulatory agencies; numerous candidates are in advanced stages of human clinical trials. Selection of drugs on the basis of DNA sequence and structure has a reduced potential for toxicity, should result in fewer side effects, and therefore should eventually yield safer drugs than those currently available. These predictions are based on the high selectivity and specificity of such molecules for recognition of their molecular targets. However, poor cellular uptake and rapid in vivo degradation of DNA-based therapeutics necessitate the use of delivery systems to facilitate cellular internalization and preserve their activity. This review discusses the basis of structural design, mode of action, and applications of DNA-based therapeutics. The mechanisms of cellular uptake and intracellular trafficking of DNA-based therapeutics are examined, and the constraints these transport processes impose on the choice of delivery systems are summarized. Finally, the development of some of the most promising currently available DNA delivery platforms is discussed, and the merits and drawbacks of each approach are evaluated.

Antisense Elements (Genetics)↗
PubMed1984

Therapeutic plasma levels of phenytoin, phenobarbital, and carbamazepine: individual variation in relation to seizure frequency and type.

The range and clinical features that influence the individual variation of the therapeutic plasma concentration of phenytoin, phenobarbital, and carbamazepine were studied in 84 epileptic patients on single-drug therapy. Complete cessation of seizures was observed at plasma concentrations of 17.9 (3 to 50) micrograms/ml phenytoin, 24.5 (3 to 43) micrograms/ml phenobarbital, and 6.5 (4.8 to 9.7) micrograms/ml carbamazepine. Fifty-one percent of the 53 patients receiving phenytoin were completely controlled at either below or above the 10 to 20 micrograms/ml range, suggesting that individual dosage adjustment is preferably based on clinical judgment rather than numerical limits of published therapeutic ranges. Fifty patients with therapeutic plasma concentrations of or above 15 micrograms/ml phenytoin, 25 micrograms/ml plasma concentrations of or above 15 micrograms/ml phenytoin, 25 micrograms/ml phenobarbital, or 6 micrograms/ml carbamazepine more often had partial epilepsies, complex partial seizures and, most markedly, a higher number of seizures in the first year of epilepsy and during the year prior to the present drug therapy, when compared with 34 patients with lower therapeutic plasma concentrations. The variation in therapeutic plasma concentration is primarily related to the type and to the severity of the individual epilepsy, as indicated by the seizure frequency at the onset of the epilepsy or prior to the treatment.

Adolescent↗
PubMed1998

[Development of antiviral therapeutic agents from traditional medicines].

Traditional medicines contain various metabolites derived from nucleic acid, protein, and lipid metabolism. Some of these specific metabolites may recognize the differences between viral and host metabolism resulting in anti-viral activity; hence traditional medicines may be useful sources for new antiviral agents. Traditional medicines can be cheaply obtained and have been orally administered as hot-water extracts. Therefore, they may be used for the prophylactic and therapeutic treatment of viral infection by drinking them, such as coffee or tea. Here we describe how the antiviral activity of traditional medicines was screened in vitro and how their therapeutic antiviral activities were verified in vivo, to obtain traditional antiviral medicines that can be clinically used. Therefore, we have selected 12 herbal extracts, from more than 250 herbal medicines, that exhibit therapeutic activities against cutaneous herpes simplex virus (HSV) type 1 (HSV-1) infection in mice. Four of the 12 augmented the therapeutic efficacy of acyclovir (ACV) in mice and showed potent anti-HSV activity against infection with ACV-resistant HSV-1 mutants in mice. These herbal extracts selectively inhibited viral DNA synthesis and showed a different mode of anti-HSV-1 action from that of ACV. They were also effective against both recurrent HSV and cytomegalovirus infections, without toxicity. Such prophylactic and therapeutic antiviral activities of the traditional medicines were verified by the purification of major active compounds. We could show new indications of traditional medicines as antiviral agents. Thus, the drinking of the extracts, in a daily tea or coffee, may be used for prophylaxis and therapy of diseases caused by herpes virus infection and improve the quality of life.

Animals↗
PubMedDate not supplied

Usefulness of therapeutic drug monitoring of antiretrovirals in routine clinical practice.

BACKGROUND: Clinical trials have shown that therapeutic drug monitoring (TDM) of antiretrovirals (ARV) improves patient care. However, little is known about the usefulness of TDM in routine practice. METHOD: We reviewed all the trough concentrations of protease inhibitors and nonnucleoside reverse transcriptase inhibitors that were performed for therapeutic failure, suspected drug toxicity, or routine purposes. RESULTS: Between 1998 and 2001, 146 TDMs were done in 109 HIV patients. Of the 48 patients with therapeutic failure, 62% had resistance to ARV with adequate ARV concentrations, 16% had insufficient drug exposure without any ARV resistance mutations, and 16% combined both resistance and suboptimal drug concentrations. Subsequent therapeutic interventions (increasing adherence and/or changing HAART) resulted in an undetectable viral load in 37.5% of the patients (14/48). Five (24%) of 21 patients with suspected drug toxicity had high drug concentrations associated with side effects. In all the cases, adverse events regressed after reduction of drug dosage. Of the 77 TDMs done for routine purposes, 26% were outside the therapeutic range. CONCLUSION: The data show that TDM of ARVs in the clinical setting provides important information that can be used to improve the management of HIV patients receiving antiretroviral therapy.

Diagnostic Tests, Routine↗
PubMed2002

Effect of therapeutic class on counseling in community pharmacies.

OBJECTIVE: To assess the effect and importance of the therapeutic class of a drug as a determinant for verbal counseling by community pharmacists. METHODS: Direct external observations (n = 1431) of pharmacist-customer interactions at the point of delivery of prescription medicines were conducted in 7 community pharmacies in Finland. Trained observers noted whether the pharmacist provided information on directions for use, mode of action, and adverse effects. To examine factors associated with counseling, a multiple logistic regression analysis was constructed, with the dependent variable being counseling of any of the 3 observed topics. In addition to therapeutic class, other independent variables were the pharmacy; pharmacist's age, gender, and degree; and the customer's age, gender, previous use of medicine, and question asking. RESULTS: Provision of counseling differed significantly according to therapeutic classes. Counseling on any of the 3 observed topics was most likely to be provided for customers with antibiotics (80%) and least likely for customers with gynecologic preparations (18%). Differences between therapeutic classes remained statistically significant when the effects of the other variables were controlled for. Other significant predictors for any verbal counseling were the pharmacy, customer's previous use of the medicine, and question asking. CONCLUSIONS: Therapeutic class is an important variable that should be included in further studies and considered when comparing studies on patient counseling in community pharmacies.

Adult↗
PubMed1999

Therapeutic commitment and role security in work with men with violence-related problems: an investigation and test of a model.

This study investigated whether therapists' therapeutic commitment and role security could be important therapist factors in therapy with those client groups that are perceived as being difficult to work with. Therapeutic commitment represents how committed therapists were to such work and role security measures to how secure they felt in their role. This study explored whether these factors could potentially explain some of the individual variation found between therapists in treatment outcomes. Following a pilot study, 209 therapists, consisting of 20 violence counsellors, 56 Relate counsellors, 58 forensic and prison psychologists and 75 clinical psychologists, completed self-report questionnaires by post about their work with violent men. Therapists' therapeutic commitment and role security were found to correlate significantly with expectations of clinical outcome on a case vignette, and with the level of violence that was usually worked with. Role security and therapeutic commitment also correlated significantly with therapists' level of experience, education about violence, role support and self-esteem. Differences existed between the professional groups on these latter factors and also in therapeutic commitment and role security. The results indicated the importance of role security in dealing with violence.

Adult↗
PubMed1999

Tracing therapeutic discourse in material culture.

Approaches to language and subjectivity from post-structuralist theory outside psychology and from deconstructive perspectives within counselling and psychotherapy have questioned the way therapeutic relationships are formed in Western culture. Discourse analysis has been developed as a methodological framework to take this questioning further, and to provide detailed readings of therapeutic patterns of meaning. Foucauldian discourse analytic approaches help us to address how we are made into selves that speak, how we experience the self therapeutically. I will elaborate this methodological framework through an analysis of a piece of text--an item of consumer packaging--tracing the contours of therapeutic discourse through a series of 20 methodological steps. Therapeutic discourse draws the reader in as the kind of subject who must feel a relationship at some depth with the (imagined) authors for the text to work. This paper thus illustrates the value of discourse analytic readings of texts, and helps us to reflect upon our commitment to discourses of counselling and psychotherapy as empowering stories and as culturally-specific patterns of subjectivity.

Counseling↗
PubMed2005

Self-reported attachment styles and therapeutic orientation of therapists and their relationship with reported general alliance quality and problems in therapy.

The aims of this study were to explore the relationship between therapists' self-reported attachment styles and therapeutic orientation with the self-reported general therapeutic alliance and therapist-reported problems in psychological therapy.A sample of 491 psychotherapists from differing therapeutic orientations responded to a postal questionnaire. The questionnaire contained standardized measures of therapeutic alliance quality, attachment behaviours, a checklist of problems in therapy, and a brief personality inventory.Therapist-reported attachment styles generally explained a significant additional proportion of the variance in alliance and problems in therapy, over and above variance explained by general personality variables. Self-reported secure attachment style was significantly positively correlated with therapist-reported general good alliance. Self-reported anxious attachment styles were significantly negatively correlated with good alliance, and significantly positively correlated with the number of therapist-reported problems in therapy. Therapeutic orientation independently predicted a small but significant amount of the variance in reported general alliance quality in addition to that explained by attachment behaviours.

Anxiety↗
PubMed2006

A comparative study on the cost of new antibiotics and drugs of other therapeutic categories.

BACKGROUND: Drug treatment is becoming more expensive due to the increased cost for the introduction of new drugs, and there seems to be an uneven distribution of medication cost for different therapeutic categories. We hypothesized that the cost of new antimicrobial agents may differ from that of other therapeutic categories and this may play a role in the stagnation of development of new antibiotics. METHODOLOGY/PRINCIPAL FINDINGS: We performed a pharmaco-economical comparative analysis of the drug cost of treatment for new agents introduced in the United States drug market in various therapeutic categories. We calculated the drug cost (in US dollars) of a ten-day treatment of all new drugs approved by the FDA during the period between January 1997 and July 2003, according to the 2004 Red Book Pharmacy's Fundamental Reference. New anti-neoplastic agents were found to be the most expensive drugs in comparison to all other therapeutic categories, with a median ten-day drug-treatment cost of US$848 compared to the median ten-day drug-treatment costs of all other categories ranging from US$29 to US$301. On the other hand, new antimicrobial drugs were found to be much less expensive, with a median ten-day drug-treatment cost of US$137 and $US85 for all anti-microbial agents and for anti-microbial agents excluding anti-HIV medications, respectively. CONCLUSIONS/SIGNIFICANCE: The drug-treatment cost of new medications varies considerably by different therapeutic categories. This fact may influence industry decisions regarding the development of new drugs and may play a role in the shortage of new antimicrobial agents in the fight against the serious problem of antimicrobial resistance.

Anti-Bacterial Agents↗
PubMed1998

Transgenic animals as drug factories: a new source of recombinant protein therapeutics.

The utility of transgenic animal bioreactors for the production of complex therapeutic proteins is based on lower production costs, higher production capacities and safer, pathogen free products. Until gene therapy becomes broadly efficacious, transgenic-derived therapeutics are the most attractive alternative for prophylactic, replacement therapy in genetic disorders, such as haemophilia. Many other disease states need short-term treatment of significant amounts of recombinant proteins that could be made amply available from transgenic animal sources. In addition, transgenic animals will provide an ideal expression system for the production of a portfolio of alternative therapeutics for patient populations developing inhibiting antibodies, for enhanced bioactivity, or for increased plasma clearance times. The FDA approval of a transgenic-derived therapeutic is still pending, but a review of Phase I & II data from antithrombin III from goat milk is encouraging, and companies are continuing to add potential therapeutics to their product pipeline.

Journal Article↗