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PubMed1998

Lamotrigine and therapeutic drug monitoring: retrospective survey following the introduction of a routine service.

AIMS: To review (retrospectively) the relationships between lamotrigine (LTG) dosage and plasma concentrations based on data generated in a routine therapeutic drug monitoring laboratory from a heterogeneous sample of patients with epilepsy. To distinguish patients taking concomitant anti-epileptic therapy which induced or inhibited drug metabolising enzymes, or a combination of both, together with LTG. To survey medical staff who use a routine LTG assay service with a view to establishing the utility of higher plasma LTG concentrations than those used in early clinical trials. METHODS: All patient assays for LTG received over a 12 month period (339 requests from 149 patients) were reviewed and relationships between dosage and concentration calculated and grouped according to concomitant antiepileptic drug therapy. The doctors requesting the tests were surveyed by questionnaire (n=40 of 67 responded). They were asked for details about the patient's seizure control, rationale used for LTG dosage adjustment and their acceptance of the proposed 'therapeutic range' adopted by the laboratory of 3-14 mg(-1). RESULTS: Linear relationships were demonstrated between LTG dosage and concentration for the 3 treatment groups (LTG plus valproic acid (VPA), LTG plus enzyme inducing antiepileptic drugs, and LTG plus VPA and inducers), however, there were significant differences between groups (P<0.001) with a 4.4 fold difference in dosage: concentration ratios between the LTG plus VPA group and the LTG plus inducers group. The questionnaire showed that the therapeutic range was well accepted by 88% of responders, none of whom considered this higher range to be wrong. CONCLUSIONS: Metabolic inhibition by VPA was shown to have a marked effect on LTG kinetics, suggesting either a significant LTG dosage reduction is required if plasma LTG concentrations are elevated, or alternatively, higher plasma LTG concentrations could be attained from lower dosages. The higher therapeutic range adopted by the laboratory (3-14 mg(-1)) was widely accepted and increasingly applied in clinical practice in the management of patients with epilepsy.

Anticonvulsants↗
PubMed1999

The therapeutic monitoring of antimicrobial agents.

AIMS: To review the basis and optimal use of therapeutic drug monitoring of antimicrobial agents. METHODS: Antimicrobial agents for which a reasonable case exists for therapeutic drug monitoring were reviewed under the following headings: pharmacokinetics, why monitor, therapeutic range, individualisation of therapy, sampling times, methods of analysis, interpretative problems and cost-effectiveness of monitoring. RESULTS: There is a strong historical case for monitoring aminoglycosides. The recent move to once-daily dosing means that criteria for therapeutic drug monitoring need to be redefined. Vancomycin has been monitored routinely but many questions remain about the most appropriate approach to this. A case can be made for monitoring teicoplanin, flucytosine and itraconazole in certain circumstances. CONCLUSIONS: The approach to monitoring aminoglycosides needs to be redefined in the light of once-daily dosing. It is premature to suggest that less stringent monitoring is necessary as toxicity remains a problem with these drugs. The ideal method of monitoring vancomycin remains to be defined although a reasonable case exists for measuring trough concentrations, mainly to ensure efficacy. Teicoplanin is monitored occasionally to ensure efficacy while flucytosine is monitored occasionally to avoid high concentrations associated with toxicity. Itraconazole has various pharmacokinetic problems and monitoring has been suggested to ensure that adequate concentrations are achieved.

Aminoglycosides↗
PubMed2001

Best practice in therapeutic drug monitoring.

It is the goal of Therapeutic Drug Monitoring (TDM) to use drug concentrations to manage a patient's medication regime and optimise outcome. Limited resources require that drug assays should only be performed when they do contribute to patient management. For this to be the case a therapeutic drug monitoring service has a far greater role than just therapeutic drug measuring. This article describes the roles and functions of a Best Practice TDM service. The features which can and should be strived for in each step of the TDM process-the decision to request a drug level, the biological sample, the request, laboratory measurement, communication of results by the laboratory, clinical interpretation and therapeutic management-are discussed.

Dose-Response Relationship, Drug↗
PubMed2001

The therapeutic monitoring of antimicrobial agents.

AIMS: To review the basis and optimal use of therapeutic drug monitoring of antimicrobial agents. METHODS: Antimicrobial agents for which a reasonable case exists for therapeutic drug monitoring are reviewed under the following headings: pharmacokinetics, why monitor, therapeutic range, individualization of therapy, sampling times, methods of analysis, interpretative problems and cost-effectiveness of monitoring. RESULTS: There is a strong historical case for monitoring aminoglycosides. The recent move to once-daily dosing means that criteria for therapeutic drug monitoring need to be redefined. Vancomycin has been monitored routinely but many questions remain about the most appropriate approach to this. A case can be made for monitoring teicoplanin, flucytosine and itraconazole in certain circumstances. CONCLUSIONS: The approach to monitoring aminoglycosides is being redefined in the light of once daily dosing. It may be that less stringent monitoring is required in some circumstances but toxicity, especially ototoxicity, remains a problem with these drugs. Monitoring to avoid high AUCs (areas under the concentration-time curve) is recommended. The ideal method for monitoring vancomycin remains to be defined although a reasonable case exists for measuring trough concentrations, mainly to ensure efficacy. Teicoplanin is sometimes monitored to ensure efficacy while flucytosine may be monitored to avoid high concentrations associated with toxicity. Itraconazole has various pharmacokinetic problems and monitoring has been suggested to ensure that adequate concentrations are achieved.

Aged↗
PubMed2003

Tumour-induced polarization of tumour vaccine-draining lymph node T cells to a type 1 cytokine profile predicts inherent strong immunogenicity of the tumour and correlates with therapeutic efficacy in adoptive transfer studies.

Previously we have shown that vaccination with the poorly immunogenic B16BL6-D5 melanoma (D5) elicits a dominant type 2 (T2) cytokine response that fails to protect the host from a subsequent tumour challenge. Here we investigated whether the inherent immunogenicity of a tumour can be correlated with its ability to bias the anti-tumour cytokine response towards either a type 1 (T1) or a T2 profile. The immune response to six tumours of different inherent immunogenicity was assayed. By isolating l-selectinlow T cells from tumour vaccine draining lymph nodes (TVDLN), it was possible to detect tumour-specific cytokine responses from both immunogenic, poorly immunogenic and non-immunogenic tumours. Immunogenic tumours (MCA-304, MCA-309, MPR-4) induced a predominant tumour-specific T1 cytokine response. In contrast, weakly (MCA-310, MPR-3) and poorly/non-immunogenic tumours (MPR-5, D5) sensitized T cells with a predominant tumour-specific T2 cytokine response. A significant correlation (P < 0.025) between immunogenicity and the ratio of tumour-specific interferon-gamma : interleukin-4 (IL-4) secretion by TVDLN T cells was identified. We then documented that non-therapeutic T cells primed by the poorly immunogenic D5, recognized "tumour-rejection" antigens and that reprogramming their cytokine response, by in vitro culture with IL-12 and anti-IL-4, to a T1 profile uncovered therapeutic efficacy. In contrast, TVDLN T cells primed by a therapeutic vaccine lose therapeutic efficacy when cultured with IL-4. These results provide insights into the development of a protective anti-tumour immune response and strengthen the hypothesis that a T1 cytokine response is critical for T-cell-mediated tumour regression.

Animals↗
PubMed1993

A therapeutic group for clients with acute mental health problems.

A therapeutic group for clients with acute mental health problems is described using a case study research design. The setting of the group is a British community mental health centre. Theoretical and research approaches to brief therapeutic work with clients are discussed. Results include qualitative descriptions of the group from the perspective of various respondents and quantitative descriptions of client attendance. The group was evaluated positively by respondents and high attendance rates indicated that the group met clients' needs. The group was primarily utilized by professionals as an addition to present services rather than as an alternative to in-patient hospitalization. However, in practice many of the clients needed some degree of professional support after ceasing to attend the group. In this study, the establishment of a therapeutic group for clients with acute mental health problems improved inter-professional relations. The ability to facilitate therapeutic groups is an important competence for mental health nurses.

Acute Disease↗
PubMed1997

The psychological characteristics of patients suffering from anorexia nervosa and the nurse's role in creating a therapeutic relationship.

This paper reviews research on the psychological characteristics of patients suffering from anorexia nervosa and that examining the therapeutic relationship. The former research suggests that anorexic patients possess a psychological profile characterized by: a phobia of weight gain and fear of loss of control; alexithymia and lack of introceptive awareness; mistrust of self and others; cognitive dysfunction; low self-esteem; and often the presence of starvation-induced depression. The latter strongly suggests that in order for a relationship to be therapeutic it needs to be characterized by: empathy; positive regard and acceptance; warmth; commitment; trust; genuineness; and be non-judgemental. The implications of these research findings regarding the nurse's role in forming a therapeutic relationship with anorexic patients is then discussed. It is seen that it is vital that nurses receive adequate education before working with such patients, and that their knowledge is regularly updated. Nurses should receive regular clinical supervision and support, in order to ensure that they are able to provide therapeutic care for such patients.

Anorexia Nervosa↗
PubMed2002

Health promotion in palliative care: the patients' perception of therapeutic interaction with the palliative nurse in the primary care setting.

AIMS: To identify and describe palliative patients' perception of factors within the interaction with the community palliative care nurse that enhance feelings of health and well-being, and to begin to define health promotion in relation to palliative nursing in the primary care setting. BACKGROUND: Health promotion may seem to be of little relevance in palliative care and for patients within its remit, and there is no definition of health promotion in relation to palliative care, yet therapeutic 'new' nursing, and its core elements of holism, egalitarianism and a humanistic approach accord with the philosophy of palliative care and are recognised as health promoting nursing practice. DESIGN/METHODS: A qualitative methodology was used. Information was obtained from 12 patients by a qualitative semi-structured interview. Data were organised and analysed using recognised guidelines for phenomenological analysis. FINDINGS: The patients identified two types of therapeutic interaction with the nurse, which enhanced feelings of health and well-being in different ways. Psychological well-being was enhanced by the humanistic and egalitarian personal interaction with the nurse, and the professional interaction focused on the disease and addressed physical problems. Although recognizing the nurses' role in the relief of physical symptoms, the patients' perception of 'feeling better' generally focussed on enhancement of psychological health and well-being. CONCLUSION: For the patients, a combination of 'new' (therapeutic) nursing and a more traditional expert-led approach resulted in the promotion of an enhanced sense of physical and psychological health and well-being, and was an integral part of community palliative care nursing. Based on the study findings, the researcher offers a definition of health promotion relevant to palliative nursing in the primary care setting, which identifies that for the patients (but with caveats related to generalizability), the practice of holistically therapeutic palliative nursing is the ideal.

Adult↗
PubMed1999

Therapeutic communication strategies used by Hong Kong mental health nurses with their Chinese clients.

Therapeutic communication is central to mental health nursing and through this process nurse-client relationships can be enhanced. In Hong Kong, mental health nurses are educated in 'western' theories and strategies in using therapeutic communication and the field of communication is predominantly Eurocentric. However, the majority of people in Hong Kong are Chinese and little research has been conducted into how Hong Kong nurses communicate with their Chinese clients. This qualitative study focused on identifying the therapeutic communication strategies used by mental health nurses with Chinese clients in Hong Kong. Three case study vignettes with some of the characteristics of Chinese culture were developed to elicit information about the strategies that respondents used in therapeutic communication. The purposive sample of 20 comprised 10 admission ward nurses and 10 community nurses from two psychiatric hospitals. All participants had at least five years post-registration experience. Content analysis revealed categories of communication and theme clusters for the nurses' response to the vignettes. The result showed a unique cultural influence emerged in communication patterns. In view of the scant nature of existing literature and studies in this area, this research provided some valuable data for further studies. Implications for mental health nursing education and practice in Hong Kong are raised, as are implications for nurses working in multicultural countries such as Australia, the UK and the USA, where there are significant numbers of Chinese clients who would benefit from nurses practising with a deeper understanding of communication strategies which are culturally bound.

Adult↗
PubMed2004

Characterization of the protective and therapeutic efficiency of a DNA vaccine encoding the major birch pollen allergen Bet v 1a.

BACKGROUND: An estimated 100 million individuals suffer from birch pollen allergy. More than 95% of birch pollen-allergic subjects react with the major birch pollen allergen Bet v 1a, and almost 60% of them are sensitized exclusively to this allergen. OBJECTIVE: DNA immunization using the Bet v 1a gene was evaluated with respect to its prophylactic and therapeutic efficacy. METHODS: A DNA vaccine containing the entire Bet v 1a cDNA under the control of a CMV-promoter was constructed. In order to estimate the protective efficiency, animals received three injections of this vaccine prior to sensitization with recombinant Bet v 1a. Vice versa, in a therapeutic approach, sensitization was followed by treatment with the DNA vaccine. RESULTS: The Bet v 1a DNA vaccine induced strong Bet v 1-specific antibody responses with a Th1-biased response type. Animals which received the DNA vaccine were protected against a following allergic sensitization with Bet v 1a. The protective effect was characterized by suppression of Bet v 1-specific immunoglobulin (Ig)E production, lack of basophil activation and enhanced interferon (IFN)-gamma expression. In a therapeutic situation, treatment of sensitized animals with DNA vaccines decreased IgE production, IgE-mediated basophil release and drastically reduced anaphylactic activity as measured by passive cutaneous anaphylaxis assays. Concerning the cellular immune response, DNA immunization induced a sustaining and dominant shift from a Th2 type response towards a balanced Th1/Th2 type response as indicated by increased IFN-gamma but unchanged IL-5 levels in lymphoproliferation assays. CONCLUSION: The results demonstrate the allergen-specific protective and therapeutic efficacy of a DNA vaccine encoding the clinically highly relevant allergen Bet v 1a indicating the suitability of this concept for the treatment of allergic diseases.

Allergens↗
PubMed2003

The therapeutic alliance: the key to effective patient outcome? A descriptive review of the evidence in community mental health case management.

OBJECTIVE: The aim of this review was to examine the level of evidence supporting the assumed link between a positive therapeutic alliance among patients and case managers and effective outcome for patients with a mental illness who are managed in community mental health services. METHOD: MedLine, PsychINFO and Social Sciences Index search of articles from 1986 to 2001 returned 84 articles and two texts. Inclusion criteria were the use of validated measures and relevance to psychiatry and community case management. RESULTS: A definite correlation exists in the psychotherapy literature between the therapeutic relationship and improved outcomes, with its potential as a prognostic indicator acknowledged. Attempts to apply the concept to patients outside the field of psychotherapy have been slow, although expansion of the concept to other forms of change-inducing therapy was a current trend. Issues of definition, quantification and measurement of the relationship caused rigorous debate in the literature. Case management research demonstrating the importance of the therapeutic relationship and 'goodness-of-fit' between patients and case managers was sparse with no published Australian studies. CONCLUSIONS: The level of evidence supporting the link between the therapeutic alliance of patients with mental illness and improved outcomes although sparse is encouraging. It indicates the potential of the alliance as a predictor of outcome for patients engaged in case management services in community mental health. Research to determine the role and effectiveness of the alliance in the patient/case manager dyad is needed to define this potential. Effectiveness of clinical practice in the case management field could be enhanced if research findings confirmed the genesis and value of the alliance in case management. Focus on relationship strategies as a clinical tool gives the clinician and service provider a potential vehicle for promoting partnerships with the seriously mentally ill person in managing their illness and optimizing their strengths in the community.

Case Management↗
PubMed2000

Therapeutic immunization against Helicobacter pylori infection in the absence of antibodies.

Helicobacter pylori is an important human pathogen. Prophylactic immunization with bacterial antigen plus an adjuvant protects mice against challenge with live H. pylori. Surprisingly, it was found that immunizations of mice already infected with Helicobacter also influenced bacterial colonization. This concept of therapeutic immunization is a novel phenomenon. Because H. pylori lives in the lumen of the stomach, it was initially hypothesized that the protective mechanism would involve induction of secretory IgA. However, work with knockout mice has demonstrated that prophylactic immunization is equally effective in mice deficient in IgA and even in microMT mice lacking B lymphocytes. Currently nothing is known about therapeutic vaccination and the effect of immunizing a host with an ongoing ineffective immune response. To address this, we infected B-cell deficient, microMT mice with H. pylori and therapeutically immunized them four times in 3 weeks with bacterial sonicate and cholera toxin adjuvant. These immunizations significantly reduced colonization by H. pylori. The antibody- negative status of the microMT mice was confirmed by ELISA. Thus, therapeutic immunization stimulates an immune response, which reduces H. pylori infection via a mechanism that is antibody independent. How this is achieved remains to be determined, but may well involve a novel immune mechanism.

Adjuvants, Immunologic↗
PubMed2002

Cervical Incompetence Prevention Randomized Cerclage Trial (CIPRACT): effect of therapeutic cerclage with bed rest vs. bed rest only on cervical length.

OBJECTIVE: To compare the effects of therapeutic cerclage and bed rest vs. just bed rest on cervical length and to relate these effects to the risk of preterm delivery. DESIGN: Cervical length was measured in patients at high risk of cervical incompetence. When a cervical length < 25 mm was measured before 27 weeks' gestation, randomization for therapeutic cerclage and bed rest vs. just bed rest was performed. After randomization, cervical length was measured weekly. For statistical analysis, t-test and Fisher's exact tests were used and P < 0.05 was considered statistically significant. RESULTS: Nineteen women were randomly allocated to receive a therapeutic cerclage and bed rest and 16 were allocated to receive bed rest only. Mean cervical lengths and mean gestational ages before randomization were comparable between both groups, overall 19.8 mm and 20.7 weeks. Cervical length was measured again at a mean gestation of 22.1 weeks. Mean cervical length (31 mm) was significantly (P < 0.0001) longer after cerclage than after bed rest only (19 mm). A cervical length > or = 25 mm was measured in 22 of the 35 included women, 16 in the cerclage group and six in the bed-rest group (P = 0.006). Of these 22 women, only one delivered before 34 weeks' gestation, which was significantly less frequent than six out of 13 women with a cervical length < 25 mm (P = 0.006). CONCLUSIONS: Therapeutic cerclage with bed rest increases cervical length more often than bed rest alone. A postintervention cervical length > or = 25 mm reduces the risk of preterm delivery in women at high risk of cervical incompetence and a preintervention cervical length < 25 mm.

Adult↗
PubMed2003

[Therapeutic application of TNF-alpha inhibitors infliximab and etanercept in inflammatory skin disorders].

BACKGROUND: The treatment of inflammatory skin diseases is at present often empirical as causal therapeutic approaches are not available because of incomplete knowledge of the immune pathogenesis. The current therapeutic approaches can induce remission, but often produce undesirable side effects. On the basis of experience gained in cytokine modulation therapy of chronic inflammatory diseases such as rheumatoid arthritis and psoriasis, the use of TNF-alpha inhibitors could represent a further, more specific and effective therapeutic option for other selected inflammatory skin diseases. PATIENTS AND METHODS: The current status of the therapeutic effect of anti-TNF-alpha blockers is discussed based on our own observations and a review of the current literature. Potential undesirable side effects and possible contraindications for this therapy are also considered. RESULTS AND CONCLUSIONS: Based on the recent findings, the use of TNF-alpha blockers seems to be promising in the treatment of therapy-resistant inflammatory dermatoses. At present, guidelines for indications and contraindications for anti-TNF-alpha treatment of inflammatory skin disorders do not exist. Such guidelines are necessary to improve the efficacy of anticytokine treatment and to reduce side effects.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

Color duplex sonography in post-therapeutic neck evaluation.

PURPOSE: Assessment of the clinical utility of color duplex sonography for post-therapeutic evaluation of the neck. PATIENTS AND METHODS: Eighty neck sides were evaluated in a prospective nonrandomized study during the post-therapeutic course. Of these, 74 previously had undergone surgery, and 60 subsequently had additional radiotherapy. The diagnostic procedures applied were clinical examination, computed tomography, positron emission tomography, and color duplex sonography. The mean observation period was 18.6 months. RESULTS: Seven of 80 (8.75%) neck sides exhibited recurrent disease, and 76.2% of the lymph nodes resected during the postoperative observation period showed malignancy. Color duplex echography could detect all lymph nodes. Sensitivity was 100%, and the specificity was 95.8%. The sensitivity and specificity of computed tomography and positron emission tomography were found to be 85.7% and 97.2%, respectively. Palpation had a sufficient specificity (95.8%) but only a very poor 14.2% sensitivity in the post-therapeutic neck. CONCLUSION: In complex tissue alterations of the post-therapeutic neck, color duplex echography is a highly sensitive and easily applied diagnostic procedure for the detection of recurrent disease. It allows a high-resolution depiction of intranodal vascularization and adjacent structures. Problems may occur in the evaluation of vessels in nodes with a diameter of 6 millimeters and below. This may impair specificity in some cases.

Head and Neck Neoplasms↗
PubMed2002

The therapeutic impact of abdominal ultrasound in patients with acute abdominal symptoms.

AIM: The technical performance of abdominal ultrasound in the investigation of acute abdominal pain has been thoroughly investigated but its therapeutic effects are less well understood. We aimed to determine the therapeutic effect of abdominal ultrasound in the investigation of acute abdominal pain. MATERIAL AND METHODS: A pre- and post-intervention observational study design was used to determine the diagnostic and therapeutic effects of abdominal ultrasound for acute abdominal pain. Referring clinicians completed a pre-ultrasound questionnaire that detailed their leading diagnosis, confidence in this and intended management in 100 consecutive adult patients. Following ultrasound a second questionnaire was completed. This again detailed the leading diagnosis, confidence in this and their intended management. Clinicians quantified the management contribution of ultrasound both for the individual case in question and in their clinical experience generally. RESULTS: The leading diagnosis was either confirmed or rejected in 72 patients and a new diagnosis provided where no prior differential diagnosis existed in 10. Diagnostic confidence increased significantly following ultrasound (mean score 6.5 pre-ultrasound vs 7.6 post-ultrasound, P < 0.001). Intended management changed following ultrasound in 22 patients; 15 intended laparotomies were halted and a further seven patients underwent surgery where this was not originally intended. Ultrasound was rated either 'very' or 'moderately' helpful in 87% of patients, with 99% of clinicians finding it either 'very' or 'moderately' helpful generally. CONCLUSION: Abdominal ultrasound has considerable diagnostic and therapeutic effect in the setting of acute abdominal pain.

Abdomen, Acute↗
PubMed2001

Interleukin 10 reduces the incidence of pancreatitis after therapeutic endoscopic retrograde cholangiopancreatography.

BACKGROUND & AIMS: Prophylactic administration of interleukin (IL)-10 decreases the severity of experimental pancreatitis. Prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in humans is a unique model to study the potential role of IL-10 in this setting. METHODS: In a single-center, double-blind, randomized, placebo-controlled study, the effect of a single injection of 4 microg/kg (group 1) or 20 microg/kg (group 2) IL-10 was compared with that of placebo (group 0), all administered 30 minutes before therapeutic ERCP. The primary endpoint was the effect of IL-10 on serum levels of amylases and lipases measured 4, 24, and 48 hours after ERCP. The secondary objective was to evaluate changes in plasma cytokines (IL-6, IL-8, tumor necrosis factor) at the same time points and the incidence of acute pancreatitis in the 3 groups. Subjects undergoing a first therapeutic ERCP were eligible for inclusion. RESULTS: A total of 144 patients were included. Seven were excluded based on intention to treat (n = 1) or per protocol (n = 6). Forty-five, 48, and 44 patients remained in groups 0, 1, and 2, respectively. The 3 groups were comparable for age, sex, underlying disease, indication for treatment, type of treatment, and plasma levels of C-reactive protein (CRP), cytokines, and hydrolases at baseline. No significant difference was observed in CRP, cytokine, and hydrolase plasma levels after ERCP. Forty-three patients developed hyperhydrolasemia (18 in group 0, 14 in group 1, and 11 in group 2; P = 0.297), and 19 patients developed acute clinical pancreatitis (11 in group 0, 5 in group 1, 3 in group 2; P = 0.038). Two severe cases were observed in the placebo group. No mortality related to ERCP was observed. Logistic regression identified 3 independent risk factors for post-therapeutic ERCP pancreatitis: IL-10 administration (odds ratio [OR], 0.46; 95% confidence interval [95% CI], 0.22-0.96; P = 0.039), pancreatic sphincterotomy (OR, 5.04; 95% CI, 1.53-16.61; P = 0.008), and acinarization (OR, 8.19; 95% CI, 1.83-36.57; P = 0.006). CONCLUSIONS: A single intravenous dose of IL-10, given 30 minutes before the start of the procedure, independently reduces the incidence of post-therapeutic ERCP pancreatitis.

Abdominal Pain↗
PubMed2004

Relationships, reality, and reciprocity with therapeutic environments: a historical case study.

This historical case study considers the reciprocity between interpersonal relationships and the immediate, structural, and demand-laden therapeutic environment in which they occur. This study draws its data from the daily diaries kept between 1814 and 1840 by the lay superintendents of the Friends Asylum for the Insane in Philadelphia. The demands of a therapeutic environment for stability and productivity, in addition to demands for safety and healing, fundamentally altered the nature of the individual relationships between patients and staff. Therefore, current practitioners must not assume the stability of their later 20th century formulations about therapeutic relationships. Rather, they must perform a careful calculus of risks and rewards as they consider the intersection of relationships, reality, and therapeutic environments.

History, 19th Century↗