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At least 991 records · Page 55Linked to original sources
PubMed1993

Non-therapeutic operations for penetrating trauma: early morbidity and mortality.

A prospective study was carried out to assess the incidence and type of complications after non-therapeutic operations for penetrating trauma. A total of 372 operations were performed on 368 patients with penetrating injuries to the abdomen (240 procedures), chest (49), neck (48) and extremities (35). There were 46 negative or non-therapeutic operations. The incidence of major complications directly related to anaesthesia or operation in this group of patients was 4 percent (two patients). The operation might have contributed to a further three major complications. The mean hospital stay for patients undergoing uncomplicated non-therapeutic operation was 4.1 days; for those with complications it was 21.2 days. It is concluded that non-therapeutic operations for penetrating trauma carry a significant morbidity rate. A policy of selective conservatism is advocated.

Abdominal Injuries↗
PubMed2006

Role of therapeutic alliance in family therapy for adolescent anorexia nervosa.

OBJECTIVE: The purpose of this study is to examine the role of therapeutic alliance in predicting treatment dropout, response and outcome in a cohort of adolescents with anorexia nervosa (AN) and their families who were treated using a manualized form of family-based therapy (FBT). METHOD: Independent assessors scored early and late therapeutic alliances for patients and parents using the Working Alliance Inventory-Observer (WAIo). Outcomes were weights and scores on the subscales of the Eating Disorder Examination at the end of 12 months of FBT. RESULTS: Therapeutic alliance throughout treatment was strong both for adolescents and for their parents. A strong early alliance with adolescents was associated with early treatment response in terms of weight gain. A strong early alliance with parents prevented dropout, whereas a strong late parental alliance predicted their child's total weight gain at the end of treatment. CONCLUSION: Therapeutic alliance in both patients and parents treated with FBT is generally strong and likely contributes to treatment retention and treatment outcome.

Adolescent↗
PubMed1987

Idiotype switching of CD4-specific monoclonal antibodies can prolong the therapeutic effectiveness in spite of host anti-mouse IgG antibodies.

Immunotherapy using murine monoclonal antibodies (mAb) is limited by the host anti-mouse IgG response. Previous investigations demonstrated that a large proportion of the anti-mouse response was specific for idiotypic determinants of the mAb. This study demonstrates the feasibility of idiotype switching of therapeutic mAb to evade this anti-idiotype response. In this way prolongation of the therapeutic effectiveness of mAb treatment can be achieved. Using different CD4-specific mAb consecutively in rhesus monkeys it was possible to obtain therapeutic effectiveness in spite of host anti-mouse IgG antibodies, provided that no anti-idiotypic antibodies were present. Anti-constant part antibodies may even enhance therapeutic effectiveness.

Animals↗
PubMed1986

Prevention of metastatic spread by postoperative immunotherapy with virally modified autologous tumor cells. I. Parameters for optimal therapeutic effects.

Effective anti-metastatic therapy was achieved in a mouse tumor model by combining surgery with post-operative immunotherapy using virus-modified autologous tumor cells. No therapeutic effect was observed when using for immunotherapy the nonmodified autologous tumor ESb, which is only weakly immunogenic and highly metastatic. The viral modification was achieved by infecting the tumor with an avirulent strain of Newcastle disease virus (NDV), which led to expression of viral antigens and to an increase in the tumor cells' immunogenicity. Parameters which were of decisive influence for success or failure of therapy were the time of operation of the primary tumor and the dose of virus which was admixed to a standard dose of irradiated tumor cells. There was a low dose optimum of NDV at about 100 hemagglutinating units per 25 X 10(6) tumor cells. The therapeutic effect observed was less pronounced if the virus was given separately from the tumor cells. Post-operative immunotherapy with NDV-modified tumor cells had the following therapeutic effects: (1) disappearance of micrometastases from visceral organs as ascertained by a sensitive bioassay; (2) life prolongation in virtually all animals when compared to controls (operated only); (3) cures in about 50% of the treated animals. The possible mechanism of this therapeutic effect and its potential for clinical application are discussed.

Animals↗
PubMed1997

Adulteration by synthetic therapeutic substances of traditional Chinese medicines in Taiwan.

The adulteration by synthetic therapeutic substances of traditional Chinese medicines has been reported on various occasions and has been a public health concern in Taiwan over the past several years. A large-scale effort was initiated in 1992 to screen traditional Chinese medicines that were suspected of adulteration with synthetic therapeutic substances. The term "adulteration" refers to traditional Chinese medicines that are tested and found to contain chemical substances not prescribed or labeled as part of the intended use. A total of 2,609 samples were collected by eight major general hospitals in Taiwan. Samples were collected through physicians' referrals during patients visits. The samples were analyzed by hospital pharmacists following the established standard procedures in comparison to references by thin-layer chromatography. An average of 23.7% (n = 618) of the samples collected from the eight hospitals were adulterated. Four samples with either a rheumatoid or an antiinflammatory indication contained six different kinds of adulterants. More than half (52.8%) of the adulterated traditional Chinese medicines contained two or more adulterants. The sources of adulterated samples and their claimed indications, as well as the most frequently detected synthetic therapeutic substances, are presented in this report. The controversies regarding the combination of synthetic therapeutic substances and traditional Chinese medicines without adequate labeling should be resolved through regulatory actions for better safety of drug use.

Acetaminophen↗
PubMed2001

Adverse reactions associated with mobile therapeutic apheresis: analysis of 17,940 procedures.

In order to evaluate the nature and frequency of adverse reactions associated with Therapeutic Apheresis (TA), database information from two large mobile apheresis services was analyzed. A total of 17,940 procedures performed on 3,583 patients were studied using an Access Database. Seventy percent (12,558) of the procedures were performed on a Fresenius AS104 blood cell separator and 30% (5,382) were performed on a COBE Spectra. The five most commonly treated diseases were Guillain-Barre Syndrome (25%), thrombotic thrombocytopenic purpura (20%), myasthenia gravis (18%), the hyperviscosity syndrome (12%), and chronic inflammatory demyelinating polyneuropathy (9%). All patients received calcium gluconate supplement during the procedures. Cardiac monitoring was used during 80% of the procedures and blood pressure monitoring was used during all procedures. All procedures were supervised by a physician. Both apheresis services fully comply with the ASFA Guidelines for Therapeutic Apheresis Providers. Adverse reactions occurred in 3.9% of all procedures. The following adverse reactions were documented: reactions related to ACD toxicity (3%), vasovagal reactions (0.5%), vascular access related complications (0.15%), reactions related to FFP (0.12%), hepatitis B from FFP (0.06%), arrhythmias (0.01%), hemolysis due to inappropriate dilution of 25% albumin (0.01%), and one death (from underlying disease) during a TA procedure (0.006%). These data demonstrate that therapeutic apheresis is associated with a low rate of side effects when performed by well-trained and certified nurses under the direction of experienced physicians, even in the diverse setting of large mobile therapeutic apheresis programs.

Blood Component Removal↗
PubMed1994

Complications of therapeutic plasma exchange: a recent assessment.

The use of therapeutic plasma exchange, particularly for management of patients with neurological disorders, has steadily increased in our hospital since 1991, thus highlighting the need for continuing quality assurance of these services. We have reviewed the hemapheresis records of all 381 therapeutic plasma exchange procedures performed on a total of 63 patients from January 1991 through December 1992. Patients were referred for therapeutic plasma exchange for the following indications: acute Guillain-Barre syndrome, 31 patients (49.2%); chronic inflammatory demyelinating polyneuropathy, 15 patients (23.8%); myasthenia gravis, five patients (7.94%); paraproteinemic neuropathy, five patients (7.94%); thrombotic microangiopathies, six patients (9.52%) and Goodpasture syndrome, one patient (1.6%). Overall, 89% of patients were treated for neurological disorders. Complications of plasma exchange were noted during 17% (n = 65) of procedures involving 49% (n = 31) of patients treated. Approximately 91% of complications were classified as mild (55.4%) or moderately severe (35.4%) and did not prevent successful completion of the procedure. These were largely related to use of citrate-containing anticoagulants and additionally may have reflected the autonomic instability of many of the neuropathy patients. All four (6.15%) severe complications and one of two fatalities were related to the use of central venous access catheters. We conclude that therapeutic plasma exchange can be performed safely with acceptable toxicity caused by mild and moderately severe complications. Major complications may be minimized by careful management of central venous catheters when required for access.

Bacteremia↗
PubMed2001

Pretreatment correlates of the therapeutic bond.

This study examined the association between pretreatment client characteristics and the therapeutic bond, which is defined as the emotional aspect of the therapeutic alliance. Three types of interpersonal problems and four indicators of emotional distress were measured and compared to the therapeutic bond and its subscales (role investment, empathic resonance, and mutual affirmation) measured early in treatment. Interpersonal problems related to being overly detached were associated with a poorer quality bond and, in particular, with a tendency to feel as if the therapist does not understand what the client is thinking and feeling (lower empathic resonance). Higher levels of distress were correlated negatively with the therapeutic bond. Analyses indicated that interpersonal problems were better predictors of the bond than was distress. The relevance of these findings for practitioners is discussed.

Adolescent↗
PubMedDate not supplied

Sustained delivery of therapeutic concentrations of human clotting factor IX--a comparison of adenoviral and AAV vectors administered in utero.

BACKGROUND: Prenatal somatic gene therapy has been considered for genetic disorders presenting with morbidity at birth. Haemophilia is associated with an increased risk of catastrophic perinatal bleeding complications such as intracranial haemorrhage, which could be prevented by gene transfer in utero. Prenatal gene therapy may be more promising than postnatal treatment, as the fetus may be more amenable to uptake and integration of therapeutic DNA and the immaturity of its immune system may permit life-long immune tolerance of the transgenic protein, thus avoiding the dominant problem in haemophilia treatment, the formation of inhibitory antibodies. METHODS: Adenovirus serotype 5-derived or AAV serotype 2-derived vectors carrying human clotting factor IX (hfIX) cDNA or a reporter gene were administered intramuscularly, intraperitoneally or intravascularly to late-gestation mouse fetuses. Both vector types were evaluated with respect to the kinetics of hfIX delivery to the systemic circulation and possible immune responses against the vector or the transgene product. RESULTS: Mice treated in utero by intramuscular injection of an adenoviral vector carrying hfIX cDNA exhibited high-level gene expression at birth and therapeutic--albeit continuously decreasing--plasma concentrations of hfIX over the entire 6 months of the study. Adenoviral vector spread to multiple organs was detected by polymerase chain reaction (PCR). Intramuscular, intraperitoneal or intravascular application of AAV vectors carrying hfIX cDNA led to much lower plasma concentrations of hfIX shortly after birth, which appeared to decline during the first month of life but stabilized in some of the mice at detectable levels. No signs of immune responses were found, either against the different viral vectors or against hfIX. CONCLUSION: This study demonstrates for the first time that sustained systemic delivery of a therapeutic protein can be achieved by prenatal gene transfer. It thus shows the feasibility of gene therapy in utero and provides a basis for considering this concept as a preventive therapeutic strategy for haemophilia and perhaps also for other plasma protein deficiencies.

Adenoviridae↗
PubMedDate not supplied

Therapeutic levels of human factor VIII in mice implanted with encapsulated cells: potential for gene therapy of haemophilia A.

BACKGROUND: A gene therapy delivery system based on microcapsules enclosing recombinant cells engineered to secrete a therapeutic protein has been evaluated. The microcapsules are implanted intraperitoneally. In order to prevent cell immune rejection, cells are enclosed in non-antigenic biocompatible alginate microcapsules prior to their implantation into mice. It has been shown that encapsulated myoblasts can deliver therapeutic levels of Factor IX (FIX) in mice. The delivery of human Factor VIII (hFVIII) in mice using microcapsules was evaluated in this study. METHODS: Mouse C2C12 myoblasts and canine MDCK epithelial kidney cells were transduced with MFG-FVIII (B-domain deleted) vector. Selected recombinant clones were enclosed in alginate microcapsules. Encapsulated recombinant clones were subsequently implanted intraperitoneally into C57BL/6 and immunodeficient SCID mice. RESULTS: Plasma of mice receiving C2C12 and encapsulated MDCK cells had transient therapeutic levels of FVIII in immunocompetent C57BL/6 mice (up to 20% and 7% of physiological levels, respectively). In addition, FVIII delivery in SCID mice was also transient, suggesting that a non-immune mechanism must have contributed to the decline of hFVIII in plasma. Quantitative RT-PCR analysis confirmed directly that the decline of hFVIII is due to a reduction in steady-state hFVIII mRNA, consistent with transcriptional repression. Furthermore, encapsulated cells retrieved from implanted mice were viable, but secreted FVIII ex vivo at three-fold lower levels than the pre-implantation levels. In addition, antibodies to hFVIII were detected in immunocompetent C57BL/6 mice. CONCLUSIONS: Implantable microcapsules can deliver therapeutic levels of FVIII in mice, suggesting the potential of this gene therapy approach for haemophilia A. The findings suggest vector down-regulation in vivo.

Animals↗
PubMed2006

Magnetic resonance angiography reveals therapeutic enlargement of collateral vessels induced by VEGF in a murine model of peripheral arterial disease.

PURPOSE: To quantify spontaneous and therapeutic arteriogenesis in vivo in a murine model of peripheral arterial disease using magnetic resonance angiography. MATERIALS AND METHODS: Male, 8-12-week-old, C57/BL6 mice underwent femoral artery ligation; 21 days later, 2 mg/kg recombinant murine VEGF165, formulated for slow release, was injected into the ipsilateral gastrocnemius. The spontaneous (following ligation) and therapeutic (following vascular endothelial growth factor (VEGF)) formation of collateral vessels was quantified using 3D magnetic resonance angiography on a small-bore 4.7T system. Therapeutically induced angiogenesis and blood flow were quantified using an in situ anti-platelet endothelial cell adhesion molecule (PECAM) 1 radioimmunoassay and radiolabeled microsphere deposition, respectively. RESULTS: Spontaneous arteriogenesis was visible in all animals five days after ligation. VEGF treatment doubled the arteriogenic response five days after treatment compared to vehicle (cross-sectional area of vessels: 0.96 vs. 0.46 mm2, P<0.01). VEGF also induced angiogenesis (PECAM1 levels 191% of vehicle, P<0.05) and increased blood flow specific to the injection site (57 vs. 7 mL/minute/100 g, P<0.05). CONCLUSION: The presented methodology allowed in vivo quantification of spontaneous arteriogenesis in a murine model of peripheral arterial disease and demonstrated that therapeutic enlargement of collateral vessels is possible with VEGF.

Animals↗
PubMed2002

Therapeutic strategies used by occupational therapists in self-care training: a qualitative study.

Self-care training is one of the most frequently used interventions in rehabilitation. However, there is a need for clear descriptions of what occupational therapists do during self-care training with clients. The aim of this qualitative study was to describe what characterizes the therapeutic strategies used by occupational therapists during self-care training. Twelve occupational therapists working with clients who had had a stroke (n = 6) or spinal cord injury (n = 6) were interviewed and asked to tell a therapeutic story focusing on the self-care training process of one client. Data were transcribed and analysed using the Empirical, Phenomenological, Psychological (EPP) method, a qualitative method that aims to describe the essence, structure and character of the studied phenomenon (that is, therapeutic strategies). The characteristics of eight intervention strategies, used by all participants during self-care training, were identified. Findings showed that the occupational therapists' strategies focused primarily on how to create a relationship built on trust with their clients, how to find the right way to motivate clients, how to support the setting of goals, and how to provide enabling occupational experience and adjust training to the needs of the client, rather than focusing on teaching clients how to use technical and compensatory strategies. The general aim for using the strategies was to support the clients in taking control of their lives again. One conclusion from this study is that occupational therapists could, through understanding the individual's unique situation, vary their strategies and adapt themselves, like a chameleon, to meeting clients' experiences and needs during self-care training. However, the therapeutic outcome of using these strategies needs to be verified in future studies focusing on clients' experiences from self-care training.

Activities of Daily Living↗
PubMed2004

Biodistribution of post-therapeutic versus diagnostic (131)I-MIBG scans in children with neuroblastoma.

BACKGROUND: To evaluate the biodistribution of therapeutic (131)I-metaiodobenzylguanidine (MIBG) and assess the sensitivity of diagnostic versus therapeutic (131)I-MIBG scans to detect metastatic disease. PROCEDURE: This retrospective study included 44 diagnostic and post-therapy scans (PTS) in 18 children with neuroblastoma treated with (131)I-MIBG (2.0-33.1 GBq). The findings of diagnostic scans (DS) (2.6-44.4 MBq) were compared to those of corresponding PTS. RESULTS: In terms of biodistribution, the PTS identified (131)I-MIBG activity in one or more patients in the following regions not detected on the DS: nasal mucosa, cerebellum, central brain, adrenals, spleen, kidneys, thyroid, salivary glands, lower halves of the lungs, bladder, bowel, and an incisional scar. Conversely, the DS identified activity in the thorax, heart, kidneys, and bladder each in one patient without being visualized on the PTS. In terms of sensitivity to detect metastatic disease, 210 lesions were seen on the PTS compared to 151 on the DS. The PTS demonstrated sites of disease not evident in the DS in 16 cases. CONCLUSIONS: The biodistribution of (131)I-MIBG is different using therapeutic doses as compared to pre-therapy doses. (131)I-MIBG imaging following high therapeutic doses often reveals sites of occult metastatic disease that may be clinically relevant.

3-Iodobenzylguanidine↗
PubMed2005

Current strategies for the development of peptide-based anti-cancer therapeutics.

The completion of the human genome sequence and the development of new techniques, which allow the visualisation of comprehensive gene expression patterns, has led to the identification of a large number of gene products differentially expressed in tumours and corresponding normal tissues. The task at hand is the sorting of these genes into correlative and causative ones. Correlative genes are merely changed as a consequence of transformation and have no decisive effects upon transformation. In contrast, causative genes play a direct role in the process of cellular transformation and the maintenance of the transformed state, which can be exploited for therapeutic purposes. Oncogenes and tumour suppressor genes are prime targets for the development of new inhibitors and gene therapeutic strategies. However, many target oncogene products do not exhibit enzymatic activity that can be inhibited by conventional small molecular weight compounds. They exert their functions through regulated protein-protein or protein-DNA interactions and might require other compounds for efficient interference with such functions. Peptides are emerging as a novel class of drugs for cancer therapy, which could fulfil these tasks. Peptide therapy aims at the specific inhibition of inappropriately activated oncogenes. This review will focus on the selection procedures, which can be employed to identify useful peptides for the treatment of cancer. Before peptide-based therapeutics can become useful, it will be necessary to increase their stability by modifications or the use of scaffolds. Additionally, various delivery methods including liposomes and particularly the use of protein transduction domains (PTDs) have to be explored. These strategies will yield highly specific and more effective peptides and improve the potential of peptide-based anti-cancer therapeutics.

Antineoplastic Agents↗
PubMedDate not supplied

Estimating the minimum therapeutically effective dose of a compound via regression modelling and percentile estimation.

Estimation of the minimum effective dose (MED) of a compound from a typical placebo-controlled dose-response study can be carried out in several ways. Current approaches compare treatment doses against a placebo dose via selected contrasts to determine the lowest dose level at which the contrast is statistically significant. Ruberg shows how this approach works for various choices of contrasts. Instead, the MTED (minimum therapeutically effective dose) might be defined as the lowest dose level that yields a therapeutic benefit to patients, on average, or to a given percentage of patients. One could use a lower confidence limit for the mean approach to determine the dose yielding (on average) a therapeutic benefit via regression modelling of the continuous treatment dose response. More importantly, a patient relevant approach would be to actually estimate regression percentiles or construct regression tolerance intervals. Such an approach addresses the question 'What percentage of patients are receiving therapeutic (yet safe) doses', instead of just knowing that a dose is effective 'on average', and thus would help to understand the distribution of patient responses at a given treatment dose. This further enables one to better evaluate the efficacy versus safety trade-off as dose increases and provides better guidelines for prescribed dose levels.

Controlled Clinical Trials as Topic↗
PubMed2005

Management of twin-twin transfusion syndrome in pregnancies with iatrogenic detachment of membranes following therapeutic amniocentesis and the role of interim amniopatch.

OBJECTIVE: Detachment of membranes may occur after therapeutic amniocentesis for twin-twin transfusion syndrome (TTTS). Subsequent amniocenteses or endoscopic fetal therapy may be hindered or made altogether impossible by this complication. The purpose of this study was to describe our experience in the assessment and management of TTTS patients with iatrogenic detached membranes (IDM). METHODS: Patients with IDM referred for fetal surgery for TTTS were considered ineligible for standard surgery and were offered different alternatives, including expectant management, serial amniocentesis, or an attempt at surgery with or without prior amniopatch. Pregnancy outcomes were compared between surgical and non-surgical patients. RESULTS: Nine hundred and forty-four patients with a diagnosis of TTTS were referred between July 1997 and December 2004, of whom 322 (34.1%) had a prior therapeutic amniocentesis. Twenty-six of the 322 patients (8%) had IDM. Ten patients opted to be managed with subsequent amniocenteses, two of which had an amniopatch. One patient had voluntary interruption of pregnancy. Fifteen patients underwent surgery, 10 of whom underwent an amniopatch. Overall, resealing of membranes occurred in 8/12 (66%) patients treated with an amniopatch. Survival of at least one fetus was greater in patients treated surgically with or without an amniopatch (12/15, 80% vs. 4/11, 36%, P = 0.04). CONCLUSION: Membrane detachment is an important complication of therapeutic amniocentesis in the treatment of TTTS. Although successful treatment of IDM can be achieved with an interim amniopatch, this alternative is not without risks. Therapeutic amniocenteses should be discouraged in patients considering endoscopic fetal surgery for TTTS.

Amniocentesis↗
PubMed1998

Therapeutic periocular vaccination with a subunit vaccine induces higher levels of herpes simplex virus-specific tear secretory immunoglobulin A than systemic vaccination and provides protection against recurrent spontaneous ocular shedding of virus in latently infected rabbits.

Rabbits latently infected with herpes simplex virus type 1 (HSV-1) were vaccinated either periocularly or systemically with a subunit vaccine (gB2 + gD2) plus adjuvant or adjuvant alone. Tear films were collected daily to measure recurrent infectious HSV-1 shedding. After systemic vaccination, the latently infected rabbits were not protected against recurrent ocular viral shedding (HSV-1-positive tear film cultures/total cultures) compared with either the systemic or periocular adjuvant controls (systemic vaccination = 49 of 972, 5.0%; systemic control = 46 of 972, 4.7%; periocular control = 43 of 930, 4.6%; P > 0.8). In contrast, latently infected rabbits vaccinated periocularly with the same vaccine had significantly reduced recurrent shedding (20 of 1026, 2.0%) compared with controls (P < 0.001) or systemic vaccination (P = 0.0002). Thus, recurrent HSV-1 shedding was significantly reduced by therapeutic local periocular subunit vaccination but not by therapeutic systemic subunit vaccination. Neutralizing antibody titers in the serum of systemically and ocularly vaccinated rabbits was similar. In contrast, HSV-specific tear secretory immunoglobulin A was significantly higher in the ocularly vaccinated group (P < 0.01). These results strongly suggest that in the rabbit, and presumably in humans, the local ocular (mucosal) immune response is much more important than the systemic immune response for therapeutic protection against recurrent ocular HSV-1. Thus development of a therapeutic vaccine against recurrent ocular HSV-1 should be directed at enhancing the local ocular (mucosal) immune response.

Animals↗
PubMed2006

Gene-expressed RNA as a therapeutic: issues to consider, using ribozymes and small hairpin RNA as specific examples.

In recent years there has been a greater appreciation of both the role of RNA in intracellular gene regulation and the potential to use RNA in therapeutic modalities. In the latter case, RNA can be used as a therapeutic target or a drug. The chapters in this volume cover the varied and potent actions of RNA as antisense, ribozymes, aptamers, microRNA and small hairpin RNA in gene regulation, as well as their use as potential therapeutics for metabolic and infectious diseases. Our group has been involved in the development of anti-HIV gene expression constructs to treat HIV. In this chapter, we address the relevant scientific and some of the commercial issues in the use of RNA as a therapeutic. Specifically, the chapter discusses delivery, expression, potency, toxicity and commercial development using, as examples, hammerhead ribozymes and small hairpin RNA.

Animals↗