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PubMed2004

Adrenomedullin gene transfer induces therapeutic angiogenesis in a rabbit model of chronic hind limb ischemia: benefits of a novel nonviral vector, gelatin.

BACKGROUND: Earlier studies have shown that adrenomedullin (AM), a potent vasodilator peptide, has a variety of cardiovascular effects. However, whether AM has angiogenic potential remains unknown. This study investigated whether AM gene transfer induces therapeutic angiogenesis in chronic hind limb ischemia. METHODS AND RESULTS: Ischemia was induced in the hind limb of 21 Japanese White rabbits. Positively charged biodegradable gelatin was used to produce ionically linked DNA-gelatin complexes that could delay DNA degradation. Human AM DNA (naked AM group), AM DNA-gelatin complex (AM-gelatin group), or gelatin alone (control group) was injected into the ischemic thigh muscles. Four weeks after gene transfer, significant improvements in collateral formation and hind limb perfusion were observed in the naked AM group and AM-gelatin group compared with the control group (calf blood pressure ratio: 0.60+/-0.02, 0.72+/-0.03, 0.42+/-0.06, respectively). Interestingly, hind limb perfusion and capillary density of ischemic muscles were highest in the AM-gelatin group, which revealed the highest content of AM in the muscles among the three groups. As a result, necrosis of lower hind limb and thigh muscles was minimal in the AM-gelatin group. CONCLUSIONS: AM gene transfer induced therapeutic angiogenesis in a rabbit model of chronic hind limb ischemia. Furthermore, the use of biodegradable gelatin as a nonviral vector augmented AM expression and thereby enhanced the therapeutic effects of AM gene transfer. Thus, gelatin-mediated AM gene transfer may be a new therapeutic strategy for the treatment of peripheral vascular diseases.

Adrenomedullin↗
PubMed1977

Neuroleptic drug levels and therapeutic response: preliminary observations with red blood cell bound butaperazine.

The authors studied neuroleptic concentration-therapeutic response curves for butaperazine (BPZ), a piperazine phenothiazine, in 10 schizophrenic patients during the first 12 days of treatment. BPZ bound to red blood cells (RBC) was more strongly correlated with therapeutic response than was plasma BPZ. RBC BPZ concentrations could be used to define a "therapeutic window", an optimun concentration for therapeutic response, above and below which favorable response diminishes. The authors emphasize the preliminary nature of the data but suggest that levels of RBC-bound neuroleptic may provide an important guide for dosage regulation in schizophrenic patients.

Administration, Oral↗
PubMed1997

Utility of the initial therapeutic alliance in evaluating psychiatric patients' risk of violence.

OBJECTIVE: Evaluation of patients' potential for violence is an important component of care in psychiatric emergency and inpatient settings. Although situational variables are widely acknowledged to influence the risk of violence by psychiatric patients, most past research has been limited to patient attributes and has neglected the interpersonal context in which violence occurs. To the authors' knowledge, this is the first study to assess a new type of situational risk factor, the quality of the initial therapeutic alliance between the therapist and patient, as a predictor of the risk of violent behavior during short-term hospitalization. METHOD: The admitting physician's written initial evaluation for each of 328 patients hospitalized on a locked inpatient unit was reviewed by using a standardized alliance scale. The checklist measures the patient's level of active collaboration with the treatment process. Acute symptoms were rated at admission by physicians using the Brief Psychiatric Rating Scale. Nurses rated aggressive behavior in the hospital with the Overt Aggression Scale. RESULTS: Patients who had a poorer therapeutic alliance at the time of admission were significantly more likely to display violent behavior during hospitalization. Logistic regression analysis showed that the quality of the initial therapeutic alliance remained a strong predictor of violence even when other clinical and demographic correlates of violence were considered concurrently. CONCLUSIONS: The results suggest a new class of situational, interactional variable--reflected in the quality of the therapeutic relationship--that may be useful in evaluating patients' potential for violence. Implications for risk management are discussed.

Adolescent↗
PubMed2000

Therapeutic limit setting in an assertive community treatment program.

OBJECTIVE: The study examined the use of therapeutic limit-setting activities by members of assertive community treatment teams with clients who had serious mental illness. METHODS: Case managers from 40 Veterans Affairs intensive psychiatric community care teams reported their use of 25 limit-setting activities with 1,564 veterans during the first six months of treatment. The 25-item measurement scale was factor analyzed, and a standard multiple regression procedure was used to regress scale scores on clients' characteristics, the frequency of case managers' contact with service providers and others, and clients' and case managers' perceptions about the therapeutic alliance. RESULTS: Case managers relied most frequently on informal verbal approaches to limit setting and relied least on formal legal restrictions. Factor analysis of the instrument, the Therapeutic Limit Setting (TLS) scale, reduced the number of items to 20 and resulted in a five-factor solution. The limit-setting factors were verbal guidance, money management, contingent withholding of services or support, enforced hospitalization, and invocation of external authorities. The TLS and its subscales were characterized by high internal consistency, modest intercorrelation, and unique relationships with variables related to clients' characteristics, the treatment process, and the therapeutic alliance. Case managers were more likely to set limits with clients who had more extensive hospitalization histories, a representative payee, recent alcohol or drug use, more arrests, and more severe symptoms. CONCLUSIONS: Case managers used a range of limit-setting strategies in assertive community treatment. Limit setting is a frequent and potentially important aspect of assertive community treatment that may be useful for comparing levels of assertiveness in assertive community treatment teams and other community-based rehabilitation services.

Assertiveness↗
PubMed1991

Perspective of power in therapeutic relationships.

Therapists can have several reasons to reflect on the helping process from a perspective of power. In effect, they all use a theory of power, be it implicit or explicit. If this theory is meant to support therapeutic thoughts and actions, it has to meet several requirements. First, it must recognize the human qualities of therapists, clients, and other people involved. Second, it must account for the complexity and dynamics of therapeutic situations; it must, for example, high-light possible shifts in power differences. Third, it must be applicable to a variety of therapeutic circumstances and systems. This means that the familiar paradigm of control, predictability, simple causality, full rationality and linearity of action must be replaced by an evolutionary paradigm that assumes continuous flows of changes between actors and factors. Some of the emerging patterns get fixed, spontaneously or artificially and become visible as shorter--or longer-lasting--stable patterns on micro- and macro-levels. Power is focussed on by an anarchistic decision-making approach. The (combinations of) people involved are depicted as living, i.e., evolving and learning systems: all actors are supposed to have their own intentions, resources, strategies, interpretations, opportunities, and development. One has to look for power inequalities between the actors on operational, organizational, structural, and cultural decision-making levels. The result is a multi-actor, multidimensional decision-making model for the therapeutic relationship that opens up new possibilities for intervention.

Decision Making↗
PubMed2005

"I feel stupid and contagious:" countertransference reactions of fledgling clinicians to patients who have negative therapeutic reactions.

Patients who are prone to having negative therapeutic reactions seem to be increasingly common in clinical practice. These patients pose special problems for graduate students, psychoanalytic candidates, and other clinicians who struggle with anxiety regarding their new role and their feelings of incompetence and helplessness associated with the belief that their therapeutic efforts will result in treatment failure. The fledgling clinician thus provides fertile ground for this kind of patient to project her or his concerned, depressed, and guilty self-representation into the clinician. The fledgling clinician, owing to an incomplete integration in her or his own internal object world, is also capable of projecting dead or damaged and dying object-representations into this kind of patient, who sometimes responds by withdrawing from or leaving treatment. It is argued that although we must acknowledge the limitations of our therapeutic technique with this kind of patient, identification and interpretation of projective identification are essential to increase the likelihood of therapeutic success. Finally, rigorous education in severe psychopathology, exploration of one's intrapsychic conflicts, and participation in individual or peer clinical supervision, are recommended, as well as an interpretative emphasis on both the deeply buried love for the internal object world as well as its destruction.

Anxiety↗
PubMed2000

The therapeutic and working alliances.

Since their introduction, the concepts of the therapeutic alliance and the working alliance have provoked debate regarding the nature and function of these alliances and the applicability and validity of the concepts. Features of these concepts as originally put forth by Zetzel and Greenson, respectively, are delineated, with emphasis on the significant distinctions between them. Their relation to degree of psychopathology is examined, especially with respect to what may be understood as the more "silent" aspects of the therapeutic alliance. Mutual identification, empathy, and role-responsiveness are stressed as constituent features of the therapeutic alliance, with the working alliance seen as possible (theoretically and clinically) only after a therapeutic alliance has to some degree been established. Both alliances are understood as intrinsic structures within the analytic process, and illustrative case material is presented.

Adult↗
PubMed1998

An application of the concept of the therapeutic alliance to sadomasochistic pathology.

This paper traces the history of the therapeutic alliance concept, examining how it has been used and misused, at times elevated to a central position and at others rejected altogether. The loss of this concept created a vacuum in classical psychoanalysis that has been filled by rival theories. The continuing usefulness of looking at the treatment process through the lens of the therapeutic alliance, particularly in relation to the manifold difficulties of working with sadomasochistic pathology, is suggested. To this end, revisions of the theory of the therapeutic alliance are suggested to address some of the difficulties that have arisen in conceptualizing this aspect of the therapeutic relationship, and to provide an integrated dynamic model for working with patients at each phase of treatment. This revised model acknowledges the complexity of the domain and encompasses the multiple tasks, functions, partners, and treatment phases involved. The utility of the revised theory is illustrated in application to understanding the sadomasochistic, omnipotent resistances of a female patient through the phases of her analysis.

Adult↗
PubMed1999

Therapeutic relationships and quality of life: association of two subjective constructs in schizophrenia patients.

Subjective quality of life is an important criterion in outcome evaluation that has been well-researched in psychiatry. By comparison, the therapeutic relationship which may also be subjectively assessed has been relatively neglected as an outcome criterion although it has predictive power in relation to outcome. This exploratory study investigated subjective quality of life and therapeutic relationships in first-admission (N = 90) and long-term (N = 168) schizophrenia patients, each at two points of time. The follow-up period was 9 months for the first-admission sample and 1.5 years for the long-term sample. A significant relationship was found between global assessments of quality of life and therapeutic relationships in long-term, but not in first-admission patients. This finding was consistent at both assessments, suggesting that therapeutic relationships may become more central to quality of life in long-term care situations and that patients' views of this relationship are increasingly embedded in their overall appraisal of life.

Adult↗
PubMed1992

Therapeutic touch and post-Hurricane Hugo stress.

This repeated-session design sought to answer questions about the effectiveness of therapeutic touch in reduction of stress for 23 individuals following a natural disaster. In addition, methodological issues related to the average length of time for a therapeutic-touch treatment and a method of documenting the nonverbal interaction between subject and toucher were investigated. Findings indicate that stressed people report themselves to be less stressed following therapeutic touch (p = .05). Time of therapeutic-touch intervention varied significantly between the touchers, with a range of 6.8 to 20 minutes. Qualitative data examining the interaction of toucher and subject raised a number of questions that require further study.

Adolescent↗
PubMed1999

Goals of home care: therapeutic, compensatory, either, or both?

This article classifies home care goals into two broad categories: therapeutic goals, in which home care providers strive for measurable improvement on parameters of physical, psychological, or social functioning and compensatory (or empowering) goals, in which home care providers strive to provide services to compensate for functional impairment, thus enabling consumers to pursue their own goals. Therapeutic goals are loosely associated with "medical models" of care and compensatory goals with "social models." From a consumer perspective therapeutic and compensatory goals are important, and artificial distinctions between the two should be eliminated. However, this merger should be effected in such a way that therapeutic approaches can be incorporated into programs with relatively low unit costs.

Community Participation↗
PubMed1986

A study on the neurotoxicity of broxyquinoline and brobenzoxaldine combination in therapeutic doses.

The neurotoxicity of a combination of broxyquinoline and brobenzoxaldine (Intestopan Forte, containing 500 mg and 100 mg of the drugs respectively per capsule) was investigated by prospective clinical and electrophysiological studies in patients and volunteer subjects given the drugs in therapeutic doses (two capsules three times a day for 5 days). Of 16 patients with intestinal amoebiasis given the drugs (study A), 13 (81.25%) were cured. Adverse effects were mild and did not affect treatment. No neurological adverse effect was reported. Neurological examinations revealed no abnormality in any patient after treatment. Seven volunteer subjects underwent medical, neurological and ophthalmological examinations, and electrophysiological studies of ulnar and peroneal nerve conduction before and after treatment with the drugs in therapeutic doses (study B). Transient paresthesias were reported by one subject on the fourth day of treatment. No medical, neurological or ophthalmological abnormality was detected in any subject after treatment. There was no significant change in motor nerve conduction velocities. There was a significant (P less than 0.001) increase in the stimulus strength for distal ulnar stimulation and a significant (P less than 0.01) decrease in stimulus duration for proximal and distal ulnar stimulation. No significant changes were seen in the peroneal nerves in these parameters. No qualitative abnormality was seen in the oscilloscopic patterns of nerve conduction after treatment. Literature on the neurotoxicity of the halogenated hydroxyquinolines is reviewed. It is concluded that broxyquinoline and brobenzoxaldine (and probably other halogenated hydroxyquinolines as well) are safe and effective in therapeutic doses; neurotoxicity is unlikely to occur when these drugs are used according to therapeutic recommendations.

Adult↗
PubMed1992

Automated therapeutic drug monitoring in an ambulatory care endocrine clinic.

OBJECTIVE: To develop and implement an automated therapeutic drug monitoring system for accessing data from endocrine clinic patients who had been prescribed insulin, oral hypoglycemic agents (OHA), or levothyroxine. DATA SOURCES: We designed a computer system to retrieve clinical data from the Medical Information System (MIS), a centralized hospital computer system, and import this information directly into a Macintosh personal computer. Physician entry of prescriptions for insulin, OHA, or levothyroxine into MIS formed the basis for a computer program to retrieve daily diagnostic and prescription information, demographics, and laboratory analyses, including blood glucose and glycosylated hemoglobin for insulin and OHA orders and free and total thyroxine, total triiodothyronine, and thyroid stimulating hormone for levothyroxine orders. The information was imported into a database program (4th Dimension). RESULTS: The system identifies laboratory values outside of predetermined therapeutic ranges, maintains an up-to-date patient profile, and edits and generates reports. Preliminary experience suggests that automation eliminates 75-90 percent of the time required to manually collect the same information, and improves the accuracy, comprehensiveness, and utility of reports. CONCLUSIONS: Automated therapeutic drug monitoring minimizes the time required to collect clinical data, alerts clinicians to potential problems, and provides a means to assess overall therapeutic management. Our methodology can be used to evaluate other medications in a variety of general or specialty clinics.

Ambulatory Care↗
PubMedDate not supplied

Is there a therapeutic or pharmacokinetic rationale for amphotericin B dosing in systemic Candida infections?

OBJECTIVE: To review the literature regarding the dosage of amphotericin B in Candida infections. The correlation or rationale of current dosing practices is assessed in light of the literature. DATA SOURCES: A MEDLINE search encompassing the years 1968-1995 was used to identify pertinent literature. Additional references were obtained from the articles retrieved from MEDLINE. STUDY SELECTION: Studies that directly assessed amphotericin B dosage and/or duration, pharmacokinetic literature dealing with plasma concentrations and amphotericin B disposition, and literature dealing with dose and/or concentration as well as clinical outcome were selected for inclusion. Additional relevant citations were used in the introductory material and discussion. DATA EXTRACTION: Although there was a large number of articles related to amphotericin B, surprisingly few large studies were designed to address the issues in question. The description of the methods and results of these heterogeneous articles are the basis of this review. Although additional controlled studies with more subjects need to be performed, the results to date provide a foundation from which to make some inferences regarding optimal use of this therapeutic modality until more definitive data become available. DATA SYNTHESIS: Despite numerous articles addressing the pharmacokinetics of amphotericin B, little is known about its tissue distribution, the rate of transfer of the drug from vascular to peripheral sites, or its terminal disposition. Less information is available regarding the relevance of pharmacokinetic parameters or serum concentrations to clinical outcome. Most of the articles mentioning dosing provide little or no justification for the doses employed. The variety of the dosages used and the heterogeneity of the populations studied make determination of dose-outcome relationships difficult. CONCLUSIONS: From the available clinical data, it appears that early initiation of amphotericin B therapy is crucial to a favorable outcome. Daily dosing initially followed by every-other-day administration of twice the daily dose is better tolerated by the patient than daily dosing and produces a similar therapeutic outcome. The drug should be continued until therapeutic endpoints have been achieved, rather than until a specific total dosage has been administered. The nephrotoxicity that occurs with amphotericin B administration is apparently reversible and should not be used as an endpoint for therapy if total dosages do not exceed 4 g. Additional well-designed, controlled trials evaluating standardized dosing methods of amphotericin B with predetermined dosing regimens and/or definitive therapeutic endpoints are needed to determine the optimal dosing approach for this agent.

Amphotericin B↗
PubMed2004

Therapeutic jurisprudence and sex offenders: a psycho-legal approach to protection.

Societal response to sex offenders is marked by uncertainty about whether punishment or treatment should occur. The distinction between punishment, prevention, and protection is useful to determine how best to assess, treat, and manage sex offenders within the criminal justice system. Once convicted, both law and psychology are concerned with sex offenders changing their behavior in order to protect the community. Therapeutic jurisprudence is a legal theory that aims to maximize therapeutic effects of the law and minimize anti-therapeutic consequences of the law. Therapeutic jurisprudence provides a framework to combine legal and psychological processes to balance prevention and protection. Legal and correctional practitioners can work together to address both community protection and offender protection concerns.

Community Mental Health Services↗
PubMed2003

A model for evaluating therapeutic response of combined cancer treatment modalities: applied to treatment of subcutaneously implanted brain tumors (N32 and N29) in Fischer rats with pulsed electric fields (PEF) and 60Co-gamma radiation (RT).

The aim of the present study is to develop a mathematical model for evaluating therapeutic response of combined treatment modalities. The study was performed in rats of the Fischer-344 strain with rat glioma N32 or N29 tumors implanted subcutaneously on the thigh of the hind leg. Pulsed electric fields, PEF, with 16 exponentially decaying pulses with a maximum electric field strength of 140 V/mm and t(1/e)= 1 ms were first applied to the tumors. Then within 5 min radiation therapy with (60)Co-gamma radiation, RT, was given in daily fractions of 5 Gy. The animals were arranged into one group of controls and 3 groups of different kind of treatments: PEF only, RT only or combination of PEF + RT. At about 4 weeks after inoculation, the tumors were given the treatment sessions during one week. In 2 experimental series with totally 52 rats with N32 tumors, of which 16 were controls, were given 4 sessions of PEF treatments and RT (totally 20 Gy). In a special experimental series with totally 56 rats with N32 tumors, of which 10 were controls, the different groups were given 1, 2, 3 or 4 treatment sessions respectively. Another strain of glioma tumor, N29 with 62 tumors of which 14 were controls was studied in 2 series given 4PEF + 4RT and 2PEF + 4RT respectively. Fitting the data obtained from consecutive measurements of tumor volume (TV) of each individual tumor to an exponential model TV = TV(0). exp[TGR.t] estimated the tumor growth rate (TGR % per day) after the first day of treatment (t = 0). The TGR of N32 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p < 0.0001), compared to RT alone (p < 0.0001) and compared to PEF alone (p < 0.001). The combined treatment of N32 gives significant effect on the tumor growth rate after 2, 3 and 4 treatment session while RT alone seems to be most efficient after one treatment of 5 Gy and PEF alone is most efficient after 2 treatments at 2 consecutive days. The TGR of N29 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p < 0.05) but the combination of 2PEF + 4RT was more effective (p < 0.005). The specific therapeutic effect STE is defined as the difference between the average tumor growth rates of controls and exposed tumors divided by the average tumor growth rate of the controls. With 4PEF treatments alone the average STE value was 0.32 for N32 tumors and 0 for N29; for 4RT alone the STE values were 0.29 and 0.42 respectively, and for combined treatments 4PEF + 4RT 0.67 and 0.17 respectively. For the N29 tumors treated with 2PEF + 4RT the STE value was 0.53. The therapeutic enhancement ratio, TER, value increase with the number of treatment sessions and the TER of the combined treatments is above 1 in two of the N32 series, which indicates a synergistic effect of 4PEF + 4RT. This work demonstrate the use of our model for analyzing the combination PEF + RT, but it can also be used for evaluation the therapeutic effects of combining RT with chemotherapy or immunogenetic therapy.

Animals↗
PubMed2005

Inducing peripheral sympathetic nerve activity by therapeutic electrical stimulation.

PURPOSE: To examine whether the activity of peripheral sympathetic nerves in animals with spinal cord injury can be controlled using therapeutic electrical stimulation. METHODS: The spinal cords of 6 Wistar rats were severed at T12/T13 disk level and were given continuous therapeutic electrical stimulation. Microneurography was used to record sympathetic nerve activity at 24, 48, and 72 hours after severing the spinal cord. RESULTS: Integrated values of muscle sympathetic nerve activity after 72 hours of therapeutic electrical stimulation revealed significantly larger potentials on the stimulated side than the non-stimulated side. Skin sympathetic nerve activity showed no difference between the 2 sides. CONCLUSION: Therapeutic electrical stimulation was found to have a facilitatory effect on the muscle sympathetic nerve activity, whereas regulatory function was activated by the sympathetic nerves.

Animals↗
PubMed2002

Therapeutic factor VIII levels and negligible toxicity in mouse and dog models of hemophilia A following gene therapy with high-capacity adenoviral vectors.

High-capacity adenoviral (HC-Ad) vectors expressing B-domain-deleted human or canine factor VIII from different liver-specific promoters were evaluated for gene therapy of hemophilia A. Intravenous administration of these vectors into hemophilic FVIII-deficient immunodeficient SCID mice (FVIIIKO-SCID) at a dose of 5 x 10(9) infectious units (IU) resulted in efficient hepatic gene delivery and long-term expression of supraphysiologic FVIII levels (exceeding 15 000 mU/mL), correcting the bleeding diathesis. Injection of only 5 x 10(7) IU still resulted in therapeutic FVIII levels. In immunocompetent hemophilic FVIII-deficient mice (FVIIIKO), FVIII expression levels peaked at 75 000 mU/mL but declined thereafter because of neutralizing anti-FVIII antibodies and a cellular immune response. Vector administration did not result in thrombocytopenia, anemia, or elevation of the proinflammatory cytokine interleukin-6 (IL-6) and caused no or only transient elevations in serum transaminases. Following transient in vivo depletion of macrophages before gene transfer, significantly higher and stable FVIII expression levels were observed. Injection of only 5 x 10(6) HC-Ad vectors after macrophage depletion resulted in long-term therapeutic FVIII levels in the FVIIIKO and FVIIIKO-SCID mice. Intravenous injection of an HC-Ad vector into a hemophilia A dog at a dose of 4.3 x 10(9) IU/kg led to transient therapeutic canine FVIII levels that partially corrected whole-blood clotting time. Inhibitory antibodies to canine FVIII could not be detected, and there were no signs of hepatotoxicity or of hematologic abnormalities. These results contribute to a better understanding of the safety and efficacy of HC-Ad vectors and suggest that the therapeutic window of HC-Ad vectors could be improved by minimizing the interaction between HC-Ad vectors and the innate immune system.

Adenoviruses, Human↗