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This self-directed learning module highlights the general concepts and advances in therapeutic heat and cold, electrotherapy, and therapeutic exercise. This article is part of the chapter on physiatric therapeutics for the Self-Directed Medical Knowledge Program Study Guide for practitioners and trainees in physical medicine and rehabilitation. Special advances include lasers in medicine and the description of the appropriate type of exercise for weight control.
The present paper describes the therapeutic use of IPPB/I in postoperative pulmonary complications with ventilation disturbances of the lung. The beneficial effects of IPPB/I are shown in chest X-rays. The suppositions for performing IPPB/I, concerning equipment, staff and organization, are explained.
Neutralizing antibodies against therapeutic proteins can be potentially harmful if the antibody blocks not only the therapeutic activities of the therapeutic protein but also the normal functions of the endogenous counterpart. Detection of the neutralizing anti-therapeutic protein antibodies generally relies on bioassays measuring changes in the biologic activity of the therapeutic protein triggered by the presence of the antibody. Most of the bioassays, particularly the cell-based in vitro assays, fail to detect neutralizing anti-therapeutic protein antibodies when the remaining therapeutic protein level in the assay samples is high. The remaining therapeutic protein, either a free molecule or an immune complex with anti-therapeutic protein antibodies, can inhibit the neutralizing activity of the antibody and prevent detection. We describe the development of a procedure that uses acid dissociation and affinity adsorption to remove therapeutic protein from assay samples. With this procedure, we can detect the presence of neutralizing anti-therapeutic protein antibodies from samples containing high levels of therapeutic protein.
In a prospective, open clinical study, the relationship between serum levels of amitriptyline (At) and nortriptyline (Nt) and the therapeutic effect after 6 weeks of treatment was investigated. Serum levels were measured by gas-liquid chromatography and the therapeutic effect was assessed by the Hamilton Depression Rating Scale (HAMD) and the Clinical Global Impression Scale (CGI). A number of 25 non-delusional, moderate to severely depressed inpatients were included. A therapeutic window relationship was detected by means of regression analysis (quadratic model). Low and high serum levels were associated with low therapeutic effect. In an intermediate range, the probability of good therapeutic effect was increased. This relationship reached significance for the serum levels of At (p < 0.05) and a trend for the sum of serum levels of At and Nt (p < 0.1). As expressed by the regression coefficient r2, about 25% to 35% of the variability of therapeutic effect was explained by serum levels. Dichotomized data sets according to limits of final values of HAMD and CGI as well as limits of a therapeutic window of 70 ng/ml and 200 ng/ml (sum of At and Nt) revealed significant differences by means of Fisher's exact test (p < 0.05). Furthermore, increased ratios of serum level of Nt per serum level of At were found to be associated with decreased therapeutic effect. Thus, the present data support the existence of a therapeutic window of serum levels of At in depression. Also taking into account other reports, this therapeutic window can be defined as being between about 70 and 220 ng/ml. The assay of serum levels of At can be used to lower the risk of unsatisfactory therapeutic outcome.
Most of the existing therapeutic antibodies that have been licensed and developed as medical agents are of the human IgG1 isotype, the molecular weight of which is approximately 150 kDa. Human IgG1 is a glycoprotein bearing two N-linked biantennary complex-type oligosaccharides bound to the antibody constant region (Fc), in which the majority of the oligosaccharides are core fucosylated, and it exercises the effector functions of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity through the interaction of the Fc with either leukocyte receptors (FcgammaRs) or complement. Recently, therapeutic antibodies have been shown to improve overall survival as well as time to disease progression in a variety of human malignancies, such as breast, colon and haematological cancers, and genetic analysis of FcgammaR polymorphisms of cancer patients has demonstrated that ADCC is a major antineoplasm mechanism responsible for clinical efficacy. However, the ADCC of existing licensed therapeutic antibodies has been found to be strongly inhibited by serum due to nonnpecific IgG competing for binding of the therapeutics to FcgammaRIIIa on natural killer cells, which leads to the requirement of a significant amount of drug and very high costs associated with such therapies. Moreover, enhanced ADCC of non-fucosylated forms of therapeutic antibodies through improved FcgammaRIIIa binding is shown to be inhibited by the fucosylated counterparts. In fact, non-fucosylated therapeutic antibodies, not including the fucosylated forms, exhibit the strongest and most saturable in vitro and ex vivo ADCC among such antibody variants with improved FcgammaRIIIa binding as those bearing naturally occurring oligosaccharide heterogeneities and artificial amino acid mutations, even in the presence of plasma IgG. Robust stable production of completely non-fucosylated therapeutic antibodies in a fixed quality has been achieved by the generation of a unique host cell line, in which the endogenous alpha-1,6-fucosyltransferase (FUT8) gene is knocked out. Thus, the application of non-fucosylated antibodies is expected to be a promising approach as next-generation therapeutic antibodies with improved efficacy, even when administrated at low doses in humans in vivo. Clinical trials using non-fucosylated antibody therapeutics are underway at present.
BACKGROUND: The aim of the present study was 1) to evaluate the possible effects of therapeutic usage of omega-3 fatty acid on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), platelet activating factor (PAF), and leukotriene B4 (LTB4) in endotoxin-induced periodontitis in rats and 2) to investigate whether prophylactic usage provides any additional benefits to therapeutic doses of omega-3 fatty acid. METHODS: Experimental periodontitis was induced by repeated injection of Escherichia coli lipopolysaccharide (LPS). Thirty-six adult male Sprague-Dawley rats were divided into four study groups: 1) saline controls; 2) LPS; 3) therapeutic omega-3 fatty acid (TO3); and 4) prophylactic plus therapeutic omega-3 fatty acid (P + TO3) groups. In TO3 group, omega-3 fatty acid was given for 15 days following induction of experimental periodontitis. In P + TO3 group, omega-3 fatty acid was started 15 days before baseline, and then periodontitis was induced at baseline and omega-3 fatty acid was continued for 15 days after baseline. On day 15 after baseline, all rats were anesthetized and sacrificed. PGE2, PGF2alpha, and LTB4 levels in gingival tissue samples were analyzed by enzyme immunoassay and PAF levels were analyzed by radioimmonoassay. Data were evaluated statistically by using parametric tests. RESULTS: LPS injection resulted in significant amount of bone loss (P<0.05). Neither therapeutic nor prophylactic plus therapeutic administration of omega-3 fatty acid with the doses and duration of therapy used in the present study was effective in preventing endotoxin-induced alveolar bone loss. TO3 group exhibited significant decreases in the gingival tissue levels of PGE2, PGF2alpha, LTB4, and PAF compared to the LPS group (P<0.05). PGE2 and PGF2alpha levels in TO3 group were similar to those of the saline group (P>0.05), while LTB4 and PAF levels were statistically higher than the saline group (P<0.05). Prophylactic plus therapeutic usage of omega-3 fatty acid provided similar levels of all these mediators to those of the saline controls (P>0.05). CONCLUSIONS: Therapeutic omega-3 fatty acid significantly reduced the gingival tissue levels of PGE2, PGF2alpha, LTB4, and PAF in experimental periodontitis. Furthermore, prophylactic usage of omega-3 fatty acid provided additional beneficial effects to the therapeutic administration by decreasing the gingival tissue levels of these mediators to levels of healthy tissue. These findings should be verified by longitudinal clinical trials investigating clinical and biochemical periodontal parameters to better define the possible role of omega-3 fatty acids in periodontal treatment.
BACKGROUND: This research arose from a concern that the recovery of patients was being hindered by a lack of understanding and emphasis on psychosocial care during hospitalization. AIMS AND OBJECTIVES: This paper describes some of the findings from a study that was undertaken to explore and describe, from the perspective of hospitalized patients in Western Australia, the perceived therapeutic effect of interpersonal interactions that were experienced during hospitalization. DESIGN: Grounded theory method. METHODS: Interviews were conducted with 40 patients who were, or who recently had been, hospitalized. Seventy-eight hours of participant observation were also performed and during that time patients and nurses were observed and informally interviewed. Relevant documentation such as nursing care plans and patient notes were also reviewed. RESULTS: Emotional comfort was identified as a therapeutic state that patients perceived as enhancing their recovery. Personal control was found to be a central feature of emotional comfort and this accounted for the way in which patients interpreted therapeutic and non-therapeutic interpersonal interactions that they encountered during hospitalization. This paper will describe the conditions that patients perceived had either promoted or inhibited their emotional comfort. These were identified as the level of security, level of knowing and level of personal value. These conditions had been affected by the interpersonal interactions that had been experienced. The characteristics of therapeutic and non-therapeutic interpersonal interactions will be described. CONCLUSIONS: The results from this study provide further insight into and understanding of the therapeutic effect of psychosocial aspects of patient care. Specifically, these results emphasize the importance that patients in hospital place on all the interpersonal interactions that they experience during hospitalization. RELEVANCE TO CLINICAL PRACTICE. The identification of the characteristics of interpersonal interactions that facilitated emotional comfort provides directions for enhancing the therapeutic potential of all interpersonal interactions experienced by patients in hospital.
PURPOSE: The goal of this study was to investigate the therapeutic potentials of combining chemotherapy with human papillomavirus (HPV) E7 subunit vaccines in an animal tumor model and to determine the underlying therapeutic mechanisms. EXPERIMENTAL DESIGN: Animals bearing HPV E6/E7-expressing tumors were treated intratumorally with a selected cytotoxic drug, cisplatin, twice at 1-week interval and s.c. with E7 subunit vaccines thrice at 1-week interval. Tumor chemoimmunoresponse was measured by tumor size. Ag-specific CTL activities and tumor histology were checked in mice under treatments. Apoptosis, in vivo T-cell subset depletion, adoptive CTL transfer, and tumor regression were used to determine the mechanisms for antitumor therapeutic effects. RESULTS: Combined therapy using cisplatin plus E7 subunit vaccines improved cure and recurrence rates of tumors and long-term antitumor immunity dramatically more than single therapy alone. In particular, both components of E7 subunit vaccines were required for induction of Ag-specific CTL as well as therapeutic synergy when combined with cisplatin. This therapeutic synergy was abrogated by depletion of CD8(+) T cells in vivo and was concomitant with histologic changes (such as heavy infiltration of lymphocytes and reduced tumor cell density). Finally, the increased sensitivity of cisplatin-treated tumors to CTL-mediated killing was found to be responsible for therapeutic synergy. CONCLUSIONS: E7 subunit vaccines plus cisplatin mediate antitumor therapeutic synergy through the increased sensitivity of cisplatin-treated tumors to CTL-mediated killing. Moreover, E7-based therapeutic vaccines have the potential to improve chemotherapy in patients with cervical cancer.
Therapeutic interchange is a process of substituting a prescribed medication with one that offers therapeutic and cost benefits. The practice not only provides short-term savings but also is associated with decreases in lengths of stay in hospitals and total hospital drug expenses. There may be medicolegal implications when FDA-approved indications differ for interchanged drugs. The potential for liability is decreased when a standard of care is met, but since standards can change, guidelines should be reviewed regularly. High-tech, high-cost drugs are sometimes appropriate for therapeutic interchange. Pharmacy and therapeutics committees should assure best value by considering indirect expenses, quality, and therapeutic outcome, as well as product cost. Therapeutic interchange programs enable pharmacy managers to neutralize or at least slow the rate of drug cost increases, ensuring appropriate utilization of resources and more favorable patient outcomes.
Ancillary professions have been called upon to account for therapeutic benefits from their services or be eliminated from the health care system. A singular focus on therapy, however, would negate the unique contribution of therapeutic recreation within, while simultaneously restricting services to health care settings. It is proposed that panic over therapeutic recreation services meeting health care goals has hindered evaluation and solidification of the leisure-based philosophy presented in the NTRS Philosophical Position Statement (NTRS, 1982). It is argued that emphasizing the leisure orientation of the philosophical position statement can secure therapeutic recreation's position within, yet, not deny services to those outside of the health care system. An overview is presented on the adequacy of the position statement philosophy for therapeutic recreation. A potential danger of attempting to explain therapeutic recreation in terms of non-leisure based philosophies is also discussed.
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This article describes a research method that measures a therapist's effectiveness by assigning a composite value to each therapeutic verbal statement during a session. The intrasubject averaging of these values is called the mean therapeutic index (sigma). In this study, whether the mean therapeutic index could be used to predict treatment outcome was investigated. A successful case and an unsuccessful case were selected for 15 therapists, and an early session for each case was coded using the mean therapeutic index. The results show that the magnitude of the effect of the mean therapeutic index, as indicated by the correlation coefficient r, was .92 (r2 = 0.85). Thus, the mean therapeutic index accounted for 85% of the variance in the classification of treatment outcome as successful or unsuccessful. The findings point to the method's potential use for clinical practice and supervision of psychotherapy.
We previously reported that E7 subunit and DNA vaccines are both capable of inducing antitumor protection through induction of antigen-specific CTL. In this study, we investigated their ability to control established tumors according to tumor size, vaccine doses, and vaccine delivery routes. Antitumor therapeutic efficacy of both vaccine types was dependent on tumor burden. However, E7 subunit vaccines induced a higher level of antitumor therapeutic activities at the tested dose compared to DNA vaccines. This was concomitant with induction of antibody, CTL, and IFN-gamma responses, as well as histologic changes (heavy infiltration of lymphocytes and presence of apoptotic bodies). In vaccine dose titration assays, 50 and 100 microg of DNA vaccines exhibited an equivalent antitumor efficacy to 0.5 and 1 microg of E7 subunit vaccines, respectively, i.e., a 100-fold difference in E7 dosage, suggesting the importance of vaccine doses for achieving antitumor immunity. Furthermore, tumors of a larger size were controlled by intratumoral injection with E7 subunit vaccines, underscoring the importance of vaccine delivery routes for antitumor therapeutic efficacy. Thus, these data suggest that antitumor therapeutic efficacy of E7 therapeutic vaccines is determined by vaccine doses, vaccine delivery routes, and tumor sizes, and that these vaccines could be another addition to conventional therapy modalities against cervical cancer.
This paper maps the differential distribution of therapeutic work within the programmes of two therapeutic communities found in psychiatric hospitals. It is shown that in one of the two communities, therapeutic work was largely restricted to the small groups and to those large groups attended by the psychiatrists. The other community displayed a distribution of therapeutic work which was spread across the whole formal weekly programme and into informal interaction outside the programme. These contrasting distributions are traced to differing patterns of internal communication which affected the ability of nurses and patients to work collaboratively with the psychiatrists.
Research and education programs in therapeutics that combine the data, organizational capabilities, and expertise of several managed care organizations working in concert can serve an important role when a single organization is not large enough to address a question of interest, when diversity in populations or delivery systems is required, and when it is necessary to establish consistency of results in different settings. Nine members of the HMO Research Network, a consortium of health maintenance organizations (HMOs) that perform public domain research, have formed a Center for Education and Research on Therapeutics (CERT), sponsored by the Agency for Healthcare Research and Quality, to conduct multicenter research in therapeutics. The CERT uses a distributed organizational model with shared leadership, in which data reside at the originating organization until they are needed to support a specific study. Extraction of data from the host computer systems, and some manipulation of data, is typically accomplished through computer programs that are developed centrally, then modified for use at each site. For complex studies, pooled analysis files are created by a coordinating center, and then analysed by investigators throughout the HMOs. It is also possible to contact HMO members when necessary. This multicenter environment has several benefits, addressing: (1) a wide array of questions about the safety and effectiveness of therapeutics, (2) the impact of efforts to change clinicians' and patients' behavior, and (3) pharmacoeconomic and pharmacogenetic questions.
Cytokine research has spawned the introduction of new therapies that have revolutionized the treatment of many important diseases. These therapeutic advances have resulted from two very different strategies. The first therapeutic strategy embodies the administration of purified, recombinant cytokines. The second relies on the administration of therapeutics that inhibit the harmful effects of upregulated, endogenous cytokines. Examples of successful cytokine therapeutics include hematopoietic growth factors (colony stimulating factors) and interferons. Prime examples of cytokine antagonists that have profoundly altered the treatment of some inflammatory disorders are agents that inhibit the effects of tumor necrosis factor (TNF). In this article, we highlight some of the studies that have been responsible for the introduction of cytokine and anti-cytokine therapies, with emphasis on the development of interferons and anti-TNF agents.