Improvement of shared decision making in integrated stroke care: a before and after evaluation using a questionnaire survey.

BACKGROUND: Shared decision making (SDM) is at the core of policy measures for making healthcare person-centred. However, the context-sensitive nature of the challenges in integrated stroke care calls for research to facilitate its implementation. This before and after evaluation study identifies factors for implementation and concludes with key recommendations for adoption. METHODS: Data were collected at the start and end of an implementation programme in five stroke services (December 2017 to July 2018). The SDM implementation programme consisted of training for healthcare professionals (HCPs), tailored support, development of decision aids and a social map of local stroke care. Participating HCPs were included in the evaluation study: A questionnaire was sent to 25 HCPs at baseline, followed by 11 in-depth interviews. Data analysis was based on theoretical models for implementation and 51 statements were formulated as a result. Finally, all HCPs were asked to validate and to quantify these statements and to formulate recommendations for further adoption. RESULTS: The majority of respondents said that training of all HCPs is essential. Feedback on consultation and peer observation are considered to help improve performance. In addition, HCPs stated that SDM should also be embedded in multidisciplinary meetings, whereas implementation in the organisation could be facilitated by appointed ambassadors. Time was not seen as an inhibiting factor. According to HCPs, negotiating patients' treatment decisions improves adherence to therapy. Despite possible cognitive or communications issues, all are convinced patients with stroke can be involved in a SDM-process. Relatives play an important role too in the further adoption of SDM. HCPs provided eight recommendations for adoption of SDM in integrated stroke care. CONCLUSIONS: HCPs in our study indicated it is feasible to implement SDM in integrated stroke care and several well-known implementation activities could improve SDM in stroke care. Special attention should be given to the following activities: (1) the appointment of knowledge brokers, (2) agreements between HCPs on roles and responsibilities for specific decision points in the integrated stroke care chain and (3) the timely investigation of patient's preferences in the care process - preferably before starting treatment through discussions in a multidisciplinary meeting.

Value-Based Stroke Rehabilitation: Feasibility and Results of Patient-Reported Outcome Measures in the First Year After Stroke.

PURPOSE: Structured application of patient-reported outcome measures (PROMs) is a key element in Value Based Healthcare. This study aimed to evaluate the feasibility of a broad set of PROMs reflecting similar patient reported health domains as proposed within the International Standard Set of Patient-Centered Outcome Measures After Stroke within the first year after stroke. METHODS: The study included consecutive stroke patients admitted to inpatient or outpatient specialized rehabilitation. PROMs were administered upon admission, discharge (inpatients only), and at 3, 6, and 12 months. PROMs included: EuroQol 5 Dimensions (EQ-5D), Stroke Impact Scale (SIS), Stroke and Aphasia Quality of Life Scale (SAQOL-39NL), Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P), Hospital Anxiety and Depression Scale (HADS), and Fatigue Severity Scale (FSS). Feasibility was defined as participation, retention, and response rates. Paired t tests were conducted to analyze their changes over time. RESULTS: Of 485 inpatients and 189 outpatients who were invited, 291 (60.0%) and 82 (43.3%) participated, of whom 45 (15.5%) and 7 (8.5%) dropped out before 12 months, respectively. Two hundred seven (71.1%) and 71 (86.6%) of the inpatients and outpatients returned the questionnaires on all or all but one time points, respectively. Between admission and 12 months statistically significant improvements of PROMs addressing general health and quality of life (EQ-5D), psychiatric functioning (HADS), motor functioning (SIS mobility), and social functioning (USER-P, SIS communication) were seen. The SIS memory scale, the SAQOL-39NL and the FSS did not show any changes. CONCLUSIONS: Participation, retention, and response rates for a comprehensive set of PROMS for stroke in patients in rehabilitation were moderate to good, with clinical improvements seen until 1 year post stroke. The SAQOL-39NL and FSS did not demonstrate changes over time and cannot be recommended for repetitive measurements in this setting. By simplifying the set of questionnaires, participation and response rates may be further enhanced.

Self-Management Education for Bipolar Disorders: A Hermeneutic-Phenomenological Study on the Tacit Knowledge of Mental Health Nurses.

Background: Self-management of bipolar disorder (BD) education is a complex nursing intervention in which patients and informal caregivers are taught to be actively involved in self-monitoring and self-regulating activities. Some studies question if nurses are sufficiently equipped to deliver these educational tasks. Other studies suggest that nurses have gathered their knowledge implicitly by experience, but to date, this tacit knowledge is not described from the experiences of mental health nurses (MHNs) in ambulant BD care. Objective: To detect the tacit knowledge used by MHNs by interpreting their experiences in delivering self-management education to people with BD and their informal caregivers. Methods: A phenomenological-hermeneutical study amongst MHNs (N = 9) from three ambulant BD care clinics in the Netherlands. Face-to-face, open, in-depth interviews guided by a topic list, were conducted and transcribed verbatim prior to the hermeneutical analysis. Findings: We found five categories resembling the complex character of self-management interventions provided by MHNs: Building a trustful collaboration, Starting a dialogue about needs and responsibilities, Explaining BD, Utilizing mood monitoring instruments, and Conceptualizing self-management of BD. Conclusion: Eventually MHNs use tacit knowledge to cope with situations that demand an outside-the-box approach. Self-management education is partially trained and partially mastered through experience. Practice implications: In order to facilitate long-term self-management of BD, the collaboration of a supporting network is essential.

Attention needed for cognitive problems in patients after out-of-hospital cardiac arrest: an inventory about daily rehabilitation care.

AIM: Recent literature and Dutch guidelines for patients with out-of-hospital cardiac arrest (OHCA) recommend screening for cognitive impairments and referral to cognitive rehabilitation when needed. The aim of this study is to assess the uptake of these recommendations for OHCA patients. METHOD: An internet-based questionnaire was sent to 74 cardiologists and 143 rehabilitation specialists involved in rehabilitation of OHCA patients in the Netherlands. The questionnaire covered: background characteristics, availability and content of cognitive screening and rehabilitation, organisation of care, experienced need for an integrated care pathway including physical and cognitive rehabilitation, barriers and facilitators for an integrated care pathway. RESULTS: Forty-five questionnaires were returned (16 cardiologists and 29 rehabilitation doctors). Thirty-nine percent (n = 17) prescribed cognitive screening. Eighty-nine percent underscores an added value of an integrated care pathway. Barriers for an integrated care pathway included lack of knowledge, logistic obstacles, and poor cooperation between medical specialties. CONCLUSIONS: In the Netherlands, only a minority of cardiologists and rehabilitation specialists routinely prescribe some form of cognitive screening in OHCA patients, although the majority underscores the value of cognitive screening in OHCA patients in an integrated care pathway. The uptake of such a care pathway seems hindered by lack of knowledge and organisational barriers.

Unlocking the observation of different proton populations in fluorinated polymers by solid-state 1H and 19F double resonance NMR spectroscopy.

Nafion proton exchange membranes (PEMs) for fuel cell applications are extensively studied and commercially applied, but their unique proton conduction capabilities are still somewhat unexplained. For studying proton dynamics in situ, molecular level spectroscopic techniques have been of limited utility so far. By solid-state 1H and 19F double resonance nuclear magnetic resonance (NMR) spectroscopy using the recently revived multiple contact cross-polarization (MC-CP) pulse sequence along with double-quantum 1H-1H filtering, high resolution proton populations distinct from the dominant water resonance were observed in Nafion for the first time. This methodology quenches signal decay due to spin-lattice relaxation in the rotating frame and enables magnetization transfer between the relatively mobile 1H and 19F spin baths in Nafion. Further studies of these previously unrevealed proton populations will lead to a better understanding of the Nafion proton conduction mechanism and proton exchange processes in general.

The effects of an 8-week computer-based brain training programme on cognitive functioning, QoL and self-efficacy after stroke.

Cognitive impairment after stroke has a direct impact on daily functioning and quality of life (QoL) of patients and is associated with higher mortality and healthcare costs. The aim of this study was to determine the effect of a computer-based brain training programme on cognitive functioning, QoL and self-efficacy compared to a control condition in stroke patients. Stroke patients with self-perceived cognitive impairment were randomly allocated to the intervention or control group. The intervention consisted of an 8-week brain training programme (Lumosity Inc.®). The control group received general information about the brain weekly. Assessments consisted of a set of neuropsychological tests and questionnaires. In addition, adherence with trained computer tasks was recorded. No effect of the training was found on cognitive functioning, QoL or self-efficacy when compared to the control condition, except for very limited effects on working memory and speed. This study found very limited effects on neuropsychological tests that were closely related to trained computer tasks, but no transfers to other tests or self-perceived cognitive failures, QoL or self-efficacy. These findings warrant the need for further research into the value of computer-based brain training to improve cognitive functioning in the chronic phase after stroke.

High survival rate of 43% in out-of-hospital cardiac arrest patients in an optimised chain of survival.

AIMS: Survival to hospital discharge after out-of-hospital cardiac arrest (OHCA) varies widely. This study describes short-term survival after OHCA in a region with an extensive care path and a follow-up of 1 year. METHODS: Consecutive patients ≥16 years admitted to the emergency department between April 2011 and December 2012 were included. In July 2014 a follow-up took place. Socio-demographic data, characteristics of the OHCA and interventions were described and associations with survival were determined. RESULTS: Two hundred forty-two patients were included (73 % male, median age 65 years). In 76 % the cardiac arrest was of cardiac origin and 52 % had a shockable rhythm. In 74 % the cardiac arrest was witnessed, 76 % received bystander cardiopulmonary resuscitation and in 39 % an automatic external defibrillator (AED) was used. Of the 168 hospitalised patients, 144 underwent therapeutic procedures. A total of 105 patients survived until hospital discharge. Younger age, cardiac arrest in public area, witnessed cardiac arrest, cardiac origin with a shockable rhythm, the use of an AED, shorter time until return of spontaneous circulation, Glasgow Coma Scale (GCS) ≥13 during transport and longer length of hospital stay were associated with survival. Of the 105 survivors 72 survived for at least 1 year after cardiac arrest and 6 patients died. CONCLUSION: A survival rate of 43 % after OHCA is achievable. Witnessed cardiac arrest, cardiac cause of arrest, initial cardiac rhythm and GCS ≥13 were associated with higher survival.

Pirandello's analogy: a source for a better understanding of the social impact of stroke.

BACKGROUND: Suffering a stroke has major implications for the patient. To understand human suffering, one should understand society. Pirandello described society as a higher entity than the individual, thereby justifying human adaptability to society. We explore a qualitative finding that suggests that social trends may influence how stroke patients prioritize aspects of their rehabilitation. METHODS: We compare a contemporary patient's experience of stroke recovery with that of a fictional character from the works of Luigi Pirandello. Both patients had two main residual symptoms: hemiparesis and aphasia. RESULTS: The rehabilitation priorities of the two patients differed, and appeared to reflect the contemporaneous demands of society. Mobility was prioritized in 1910; communication was prioritized in 2010. However, essential aspects of 'being a stroke patient' remained unchanged; both patients retained a sense of self and both coped emotionally by being hopeful. CONCLUSIONS: We conclude that stroke patients respond to society's contemporaneous demands and expectations. Currently, society demands participation in a large social environment and this is reflected in stroke patients' priorities. This analogy could enable medical professionals to better understand the social impact of stroke, and consequently offer appropriate interventions to improve rehabilitation outcomes for individual patients.

Caregivers experiences of nursing care for relatives hospitalized during manic episode: A phenomenological study.

PURPOSE: To describe the experiences of informal caregivers with the nursing care received by relatives hospitalized for mania. DESIGN AND METHODS: Multicenter phenomenological study using open interviews. Data were analyzed using the Stevick-Colaizzi-Keen method. FINDINGS: The essence of the experiences was the importance of communication, about being informed and involved in treatment during hospitalization of their relative. The experiences depended on the nature of the relation between participant and relative. PRACTICE IMPLICATIONS: Nurses should listen to caregivers' experiences, inquire about the expectations of caregivers regarding nursing care, and advise informal caregivers on how to take care of their relatives.

Show yourself, a short film to show professionals at an admission ward your 'euthymic being' during an admission for mania.

BACKGROUND: The progress and recovery of a patient with mania during hospitalization is differently seen by professionals working at an admission ward and by relatives of the patient. Professionals often indicate that the situation of the patient is improving while relatives estimate the improvement to be minimal in relation to the recovery of the patient. OBJECTIVE(S): To develop an intervention to give professionals at an admission ward an impression of the patient in a euthymic mood state to provide professionals with information to plan and conduct individualized patient centred care. METHODS: Professionals, patients, and relatives were individually interviewed about the preferable content and use of a film in which patients' shows their 'euthymic being'. Content analysis was performed. RESULTS: An outline for the content and use of the film was developed. CONCLUSIONS: The intervention holds promise for clinical practice, but further development and testing is necessary.

Illness perceptions of stroke survivors: Predictors and changes over time - A 1 year follow-up study.

OBJECTIVE: To describe the illness perceptions (IP) of stroke patients in the first year post stroke; to identify patient clusters with comparable IP trajectories and determine their associations with health. METHODS: This prospective study included consecutive stroke patients after medical rehabilitation. Three and 12 months post stroke they completed the Brief Illness Perception Questionnaire (B-IPQ) and questionnaires on physical and mental health. All eight IP and their changes over time were described. Clusters of patients with comparable IP trajectories were constructed by k-means clustering, with subsequent comparison of patient characteristics. Multivariable logistic regression analyses were conducted to determine the association between IP clusters and 12-month mental health. RESULTS: Hundred-and-eighty-four patients were included (men n = 107 [58.2%]; mean age 61.1 [SD 12.7] years). At 3 months, the scores of the IP coherence (mean 3.0, SD 2.3) and treatment control (mean 3.2, SD 2.5) were lowest (best), and consequences (mean 6.1, SD 2.8) and anticipated timeline (mean 6.0, SD 2.7) were highest (worst). At 12 months, the timeline and treatment control scores had significantly worsened. Three clusters of the trajectories of IP were identified, and designated as 'favourable', 'average', and 'unfavourable'. The unfavourable cluster was significantly associated with worse physical and mental health at 3 months (unadjusted) and depressive symptoms at 12 months. CONCLUSION: Stroke patients' IP partly changed between 3 and 12 months post stroke. Patients with an unfavourable IP trajectory had a higher chance of depressive symptoms at 12 months. Illness perceptions could be considered as an additional target of treatment.

Family caregiving in bipolar disorder: caregiver consequences, caregiver coping styles, and caregiver distress.

AIMS: This study investigated the consequences caregivers of outpatients with bipolar disorder are confronted with, the distress they experience and their coping styles. METHODS: Caregivers (n = 115) were asked to complete the Involvement Evaluation Questionnaire (IEQ) to measure caregivers' consequences, the Utrecht Coping List (UCL) to measure caregivers' coping styles, and the 12-item General Health Questionnaire (GHQ-12) to measure caregiver distress. Scale (sub)scores were calculated and relationships between the results were explored. RESULTS: Caregiver consequences were found to be limited, although approximately 30% reported distress. Male caregivers used a more avoiding coping style and undertook activities to provide diversion. Female caregivers used a less active approach and sought less social support. Correlations were found between the IEQ overall score and its subscales 'tension' and 'worrying' and the UCL subscales 'palliative reaction pattern' and 'passive reaction pattern'. Distress appears to occur more often in caregivers who report more consequences, tend to use a more avoiding coping style, and have a more passive reaction pattern. CONCLUSIONS: Clinicians should assess symptoms of caregiver distress. When caregiver distress is noticed, efforts should be undertaken to support the caregiver and teach them skills to cope effectively with the consequences they experience in order to stay well.

Radiography of the distal extremity of the manus in the donkey foal: Normal images and quantitative characterization from birth to 2 years of age: A pilot study.

This study describes a radiographic survey of the anatomical development of the distal extremity of the manus in the donkey from 0 to 2 years of age. The right distal limb of 10 donkey foals, born in the spring of 2012, underwent radiographs every month for the first 6 months of age and every 3 months during the following 18 months. Latero-medial radiographs with and without barium marker at the coronary band and dorso-palmar radiographs with both front feet in weight bearing were obtained. The distal physis of the third metacarpal bone and the proximal physis of the proximal phalanx (phalanx proximalis) were closed at the mean age of 18.6 months. The distal physis of the proximal phalanx appeared as a clear radiolucent line at 2 weeks of age and was still subtly visible in some donkeys at 24 months. The proximal physis of the middle phalanx (phalanx media) was closed at the mean age of 16.7 months. The distal physis of this phalanx was visible at birth, but closed at 4 days. The distal phalanx (phalanx distalis) was triangular at birth. At the age of 20-21 months, the palmar processes (processus palmares) were both developed. The navicular bone (os sesamoideum distalis) was developed at the mean age of 9 months. The proximal sesamoid bones (ossa sesamoidea proximalia) were seen in continuously development during the 24 months. It seems that the physes in the distal extremity of the manus in the donkey close at an older age than the physes in the horse.

Adherence of stroke patients with an online brain training program: the role of health professionals' support.

Background Computer-based cognitive rehabilitation is used to improve cognitive functioning after stroke. However, knowledge on adherence rates of stroke patients is limited. Objective To describe stroke patients' adherence with a brain training program using two frequencies of health professionals' supervision. Methods This study is part of a randomized controlled trial comparing the effect of the brain training program (600 min playtime with weekly supervision) with a passive intervention in patients with self-perceived cognitive impairments after stroke. Patients randomized to the control condition were offered the brain training after the trial and received supervision twice (vs weekly in intervention group). Adherence was determined using data from the study website. Logistic regression analyses were used to examine the impact of supervision on adherence. Results 53 patients allocated to the intervention group (group S8; 64% male, mean age 59) and 52 patients who were offered the intervention after the trial (group S2; 59% male, mean age 59) started the brain training. The median playtime was 562 min (range 63-1264) in group S8 vs. 193 min (range 27-2162) in group S2 (p < 0.001, Mann Whitney U). Conclusions The overall adherence of stroke patients with a brain training was low and there are some implications that systematic, regular interaction with a supervisor can increase training adherence of stroke patients with a restitution-focused intervention performed at home.

Self-reported care needs of outpatients with a bipolar disorder in the Netherlands.

The care needs of patients with a bipolar disorder have not been studied to date. In the present research, the care needs, care received and unmet care needs for a population of outpatients with a bipolar disorder in the Netherlands are described. The participants (n = 157) completed the Need for Care Questionnaire and a questionnaire addressing various demographic and clinical characteristics. The results show the care needs to mainly involve the domains of psychological help, psychiatric help and social functioning. Unmet needs are frequently reported for all domains and found to be particularly frequent for needs on social functioning. Some significant associations between source of income, number of hospitalizations and involvement of community psychiatric nurses, on the one hand, and reported care needs, on the other hand, are identified and discussed. Incorporation of needs assessment into the treatment process is recommended in the form of structured questionnaires which can also then be used to guide and evaluate the treatment process. Future research should focus on the identification of the specific risk factors for particular care needs and thereby work to minimize the occurrence of such risk factors and promote early intervention efforts to reduce the burden on patients and their relatives.

Burden, coping and needs for support of caregivers for patients with a bipolar disorder: a systematic review.

This study was aimed to highlight the factors which influence experienced burden, coping and needs for support of caregivers for patients with a bipolar disorder. Research articles meeting content and methodological quality criteria from January 1995 through October 2005 were reviewed. High objective and subjective burden is experienced by these caregivers. Subjective burden is extremely influenced by illness beliefs. High burden is associated more with severity of symptoms (than diagnosis), difficulties in the relationship with patient, lack of support and stigma. Coping is influenced by appraisal and burden. Different phases in the process of caregiving require different coping mechanisms. Little research is available on effectiveness of coping mechanisms and needs for support. Suggestions are nevertheless found in the literature for professional support. Caregivers of patients with a bipolar disorder experience high burden and try to cope in different ways. Little research is available on coping styles and needs for support. However, recommendations can be made to increase support for these caregivers.

Identifying and describing patients' learning experiences towards self-management of bipolar disorders: a phenomenological study.

ACCESSIBLE SUMMARY: Existing evidence suggest that patient education in promoting self-management strategies of bipolar disorder (BD) is effective. However, results across the full range of service users with BD vary. Learning experiences of service users look to be a crucial factor to take into account when designing, delivering, and evaluating effective interventions that promote self-management in chronic illness. What learning activities service users actually undertake themselves when self-managing BD that might explain varying success rates, and guide future self-management educational programmes has not been examined. Unlike previous studies that suggest that outcomes in self-management depend on individual learning activities, the current study found that learning to self-manage BD takes place in a social network that functions as a learning environment in which it is saved for service users to make mistakes and to learn from these mistakes. Especially, coping with the dormant fear of a recurrent episode and acknowledging the limitations of an individual approach are important factors that facilitate this learning process. Practitioners who provide patient education in order to promote self-management of BD should tailor future interventions that facilitate learning by reflecting on the own experiences of service users. Community psychiatric nurses should keep an open discussion with service users and caregivers, facilitate the use of a network, and re-label problems into learning situations where both play an active role in building mutual trust, thereby enhancing self-management of BD. ABSTRACT: Existing evidence suggest that self-management education of bipolar disorder (BD) is effective. However, why outcomes differ across the full range of service users has not been examined. This study describes learning experiences of service users in self-managing BD that provide a possible explanation for this varying effectiveness. We have conducted a phenomenological study via face-to-face, in-depth interviews, guided by a topic list, along service users with BD I or II (n = 16) in three specialised community care clinics across the Netherlands. Interviews were digitally recorded and transcribed verbatim prior to analysis in Atlas.ti 7. Unlike existing studies, which suggest that individual abilities of service users determine outcomes in self-management of BD, the current study found that self-management of BD is a learning process that takes place in a collaborative network. We identified five categories: acknowledgment of having BD, processing the information load, illness management, reflecting on living with BD, and self-management of BD. The success of self-management depends on the acknowledgment of individual limitations in learning to cope with BD and willingness to use a social network as a back-up instead. Especially, the dormant fear of a recurrent episode is a hampering factor in this learning process.

Cognitive problems in patients in a cardiac rehabilitation program after an out-of-hospital cardiac arrest.

OBJECTIVE: Estimate prevalence of cognitive problems due to hypoxic brain injury in out-of-hospital cardiac arrest (OHCA) survivors referred for cardiac rehabilitation and association with quality of life as well as autonomy and participation. DESIGN: Prospective cohort study. METHOD/DESIGN: Consecutive OHCA patients. The Mini-Mental State Examination (MMSE), Cognitive Failures Questionnaire (CFQ) and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) were administered 4 weeks after the OHCA. Cognitive problems were defined if MMSE <28, CFQ >32 or IQCODE >3.6. The Impact on Participation and Autonomy Questionnaire (IPAQ) (participation/autonomy), the SF-36 Health Survey (SF-36) (quality of life) and the Hospital Anxiety Depression Scale (HADS) (anxiety/depression) were administered. Correlations between cognitive problems and participation/autonomy and quality of life were calculated. RESULTS: 63 of 77 patients were male (82%), median age 59 years (range 15-84). MMSE median 29 (interquartile range 28-30), CFQ mean 20.9 (SD 9.4) and IQCODE mean 3.1 (SD 0.2). Eighteen patients (23%) scored positive for cognitive problems. Significant correlations were found between MMSE and IPAQ: autonomy inside (r = -0.38), family role (r = -0.26), autonomy outside (r = -0.32), social relations (r = -0.38) and social functioning (r = 0.32). MMSE was related to SF-36: social functioning (r = 0.32). The CFQ was related to IPAQ: autonomy outdoors (r = 0.29) and SF-36: bodily pain (r = -0.37), vitality (r = -0.25), mental health (r = -0.35) and role emotional (r = -0.40). The IQCODE was related to IPAQ: autonomy indoors (r = 0.26) and to SF-36: vitality (r = -0.33) and social functioning (r = -0.41). CONCLUSION: Twenty-three percent of the patients referred for cardiac rehabilitation showed cognitive problems. Associations were found between cognitive problems and several aspects of participation/autonomy and perceived quality of life.

Feasibility of adenovirus-mediated nonsurgical synovectomy in collagen-induced arthritis-affected rhesus monkeys.

Gene transfer to synovial tissue by adenoviral vectors (Ad) was studied in vitro in cultured human synoviocytes and in vivo in seven primates with arthritis. Hyperplastic synovium was efficiently transduced with Ad.lacZ in vitro and in vivo in rhesus monkeys with collagen-induced arthritis, whereas chondrocytes were not transduced. Intraarticular injection of recombinant Ad harboring the luciferase gene showed the presence of reporter gene products only in Ad-injected joints. In addition, the feasibility of synovectomy by Ad harboring the herpes simplex virus thymidine kinase gene (tk) was studied. In vitro infection of synovium from rheumatoid arthritis patients with Ad.TK, followed by administration of ganciclovir, resulted in death of >90% of the synoviocytes. By mixing Ad.TK-infected with noninfected cells, it appeared that the presence of 10% infected synoviocytes resulted in the killing of more than 85% of the synoviocytes, demonstrating a substantial bystander effect. Intraarticular injection of Ad.TK in the knees of rhesus monkeys with arthritis, followed by treatment with ganciclovir for 14 days, resulted in increased apoptotic cell death in the synovium of Ad.TK-injected as compared with noninjected joints and ablation of the synovial lining layer. The procedure revealed no toxic side effects. These data suggest that nonsurgical synovectomy by tK gene therapy is feasible.

Isolation and flow cytometric analysis of the free lymphomyeloid cells present in murine liver.

Recruitment of circulating lymphomyeloid cells in the liver during infection often plays a critical role, mediating control or exacerbation of the pathogen growth. This paper describes a simple and rapid technique to recover these lymphomyeloid cells from a normal or an infected liver. After portal perfusion with saline buffer, the liver is gently dissociated on steel screens and the resulting cell population spun in 35% Percoll in 100 IU/ml Calciparine to remove all nuclei and cell debris: the recovery of a pure liver lymphomyeloid cell population is usually achieved in 40-60 min. Phenotypic and functional analysis could then be easily carried out on this cell population. This methodology was applied to normal mouse liver: flow cytometric analysis of the purified free lymphomyeloid cells showed the presence of T lymphocytes (46% +/- 3 with a CD4/CD8 ratio of 2.8), B lymphocytes (20% +/- 2 IgG and 30% IgM positive) and myelomonocytic cells (14% +/- 2 complement receptor type III positive).