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PubMed2003

The evolution in therapeutic contact lenses.

Therapeutic soft contact lenses were first approved in the 1970s, but the variety of available materials and parameters continues to evolve. Currently, the armamentarium of therapeutic contact lenses allows the clinician to select lenses that not only protect the corneal surface but also assist in modulation of the healing process. This article summarizes the available contact lenses, the conditions most amenable to treatment, and the decision-making process that allows optimal selection of a therapeutic contact lens for a specific patient. Many of the hydrophilic soft contact lenses used for cosmetic correction are not approved for therapeutic use but have been used in an off-label manner as therapeutic lenses. Communicating with the patient is important when recommending the use of a therapeutic contact lens, explaining the goals of therapy, warning about the risks contingent upon contact lens use, and determining whether the lens is being used in an off-label fashion. The advances in contact lens technology have opened new options for use of therapeutic contact lenses. With a new generation of high-Dk lenses whose makers promise fewer limiting problems of vascularization and infection, the utility of the older, traditional therapeutic lenses can be enhanced and the more selective application of individual lenses can be permitted. By considering the healing objectives of the particular treatment plan for a specific patient, greater control of the endpoint and timeframe of therapy is now possible.

Contact Lenses, Hydrophilic↗
PubMed2003

Therapeutic contact lenses: the role of high-Dk lenses.

Currently, the armamentarium of contact lenses that can be used for therapeutic effect provides a wider selection of lenses than ever before. If the therapeutic goal is protection and healing of the corneal epithelium, epithelial or stromal edema is best avoided, and the selection of a high-Dk silicone hydrogel (balafilcon A, lotrafilcon A) lens or a very thin membrane-type lens (crofilcon) is the best choice. If the goal is surface protection as well as stimulation of stromal wound vascularization, selection of a low-water content, thick, hydrophilic lens is the better option. If the patient is prone to lens loss or requires frequent replacement of the therapeutic lens, a prudent economic decision is to select a daily disposable moderate-water content lens. Specific circumstances may mandate the selection of a specific therapeutic lens. Patients with a prior history of active giant papillary conjunctivitis may be better served by the use of a crofilcon glyceryl methacrylate lens, which has a lower incidence of this complication. Patients who have dry eye may benefit from a higher-water content lens if adequate unpreserved tear supplementation is provided with or without punctal occlusion. The options when selecting a therapeutic contact lens are wider than ever before. Although the new generation of high-Dk lenses promises fewer limiting problems of vascularization and infection, one can use the older traditional therapeutic lenses when induced vascularization of the cornea is needed or when an economic necessity exists. Not all of the available lenses are FDA approved for therapeutic use, and such wear is an off-label use. The patient should be informed of the goal of therapy as well as the benefits and risks of therapeutic contact lenses.

Contact Lenses↗
PubMed2004

Nurses and the 'therapeutic relationship': Caring for adolescents with anorexia nervosa.

BACKGROUND: Research studies suggest that hospital programmes for young people diagnosed with anorexia nervosa have high readmission rates and limited effectiveness. Nurses caring for these adolescents face a particular set of problems in seeking to establish therapeutic relationships. AIM: This paper reports a study with the original aim of providing rich data on the development of therapeutic relationships between adolescents diagnosed with anorexia and paediatric nurses. However, it was discovered that paediatric nurses were struggling to develop therapeutic alliances with these adolescents. The study was then modified to explore the difficulties and obstacles hindering the formation of therapeutic relationships in this context. METHOD: The study used naturalistic inquiry. The 10 participants were Registered Nurses from the acute wards of an Australian children's hospital with at least 2 years' experience of caring for adolescents with anorexia nervosa. The data were collected using semi-structured interviews that were recorded on audiotape and then thematically analysed both manually and with the aid of the NUD*IST computer package. FINDINGS: Participants described how they struggled to develop therapeutic relationships in this clinical environment. Three themes emerged: (1) 'Struggling for understanding' explores the difficulties nurses experienced in coming to terms with the complexities of a diagnosis of anorexia nervosa and its recovery processes. (2) 'Struggling for control' examines the power struggle between nurses and patients and the mutual distrust that often developed between them as a consequence of this struggle. (3) 'Struggling to develop therapeutic relationships' describes the difficulties some nurses had in establishing therapeutic alliances with these adolescents. CONCLUSION: Recommendations are made for improving the nursing component of hospital treatment programmes for adolescents with anorexia nervosa in the direction of more genuinely therapeutic relationships.

Adolescent↗
PubMed2001

The therapeutic relationship: historical development and contemporary significance.

The therapeutic relationship is a concept held by many to be fundamental to the identity of mental health nurses. While the therapeutic relationship was given formal expression in nursing theory in the middle of the last century, its origins can be traced to attendants' interpersonal practices in the asylum era. The dominance of medical understandings of mental distress, and the working-class status of asylum attendants, prevented the development of an account of mental health nursing based on attendants' relationships with asylum inmates. It was left to Peplau and other nursing theorists to describe mental health nursing as a therapeutic relationship in the 1940s and later. Some distinctive features of colonial life in New Zealand suggest that the ideal of the attendant as the embodiment of bourgeoisie values seems particularly unlikely to have been realized in the New Zealand context. However, New Zealand literature from the 20th century shows that the therapeutic relationship, as part of a general development of a therapeutic discourse, came to assume a central place in conceptualizations of mental health nursing. While the therapeutic relationship is not by itself a sufficient basis for professional continuity, it continues to play a fundamental role in mental health nurses' professional identity. The way in which the therapeutic relationship is articulated in the future will determine the meaning of the therapeutic relationship for future generations of mental health nurses.

History, 19th Century↗
PubMed2005

Do dysphagic patients with an absent pharyngeal swallow have a shorter survival than dysphagic patients with pharyngeal swallow? Prognostic importance of a therapeutic videoradiographic swallowing study (TVSS).

PURPOSE: To study survival in two groups of dysphagic patients--one group unable to elicit the pharyngeal stage of swallow (APS) and another group with pharyngeal swallow (WPS)--and to compare recommendations regarding nutrition and therapeutic strategies based on the therapeutic swallowing study. MATERIAL AND METHODS: In this retrospective study, the records of dysphagic patients who have undergone a therapeutic videoradiographic swallowing study (TVSS) were reviewed. Forty patients without pharyngeal swallow were matched for age and gender with 40 patients with pharyngeal swallow; altogether 80 patients were included in the study. Survival was registered at 3, 12, and 72 months after the TVSS. RESULTS: In this study, the APS group had a significantly shorter survival time (P=0.0030) compared to the WPS group when followed-up at 12 months. In the APS group, most patients (37.5% (15/40)) died within the 3 months after TVSS. At 72 months, 62.5% (25/ 40) of the patients in the APS group had died. In the WPS group, 5% (2/40) had died within 3 months and 47.4% (19/40) after 12 months. At 72 months, 52.5% (21/40) of the patients in the WPS group had died. Regarding nutritional and therapeutic recommendations based on TVSS, 34/40 in the APS group were recommended no oral intake. Eighteen naso-gastric tubes were placed directly after TVSS. The therapeutic strategies recommended were head-positioning, thermal tactile stimulation, and tongue exercises (in 8 patients). In the WPS group, all patients were recommended oral intake. Diet modification was recommended in 29 patients. The therapeutic strategies recommended were head-positioning, thermal tactile stimulation, tongue exercises, supraglottic swallow, and effortful swallow (in 24 patients). CONCLUSION: Patients unable to elicit the pharyngeal stage of swallow had a shorter survival time than patients with pharyngeal swallow, probably due to a more severe underlying disease. Tube feeding was more frequent in the APS group. Fewer therapeutic strategies were recommended compared to the WPS group. In the WPS group, diet modification was frequent. Several patients had different therapeutic strategies. At the end of the study, 8/40 patients (20%) in the APS group had recovered and regained the ability to elicit the pharyngeal stage of swallow. All eight had achieved active swallowing rehabilitation.

Adult↗
PubMed2006

Pediatric critical care community survey of knowledge and attitudes toward therapeutic hypothermia in comatose children after cardiac arrest.

OBJECTIVE: Therapeutic hypothermia improves neurologic outcome and survival after adult out-of-hospital cardiac arrest. To help us design a prospective hypothermia trial in children, we developed a survey to assess current knowledge and attitude of pediatric critical care providers regarding therapeutic hypothermia and potential impediments to implementing a prospective study. DESIGN: Anonymous survey. SETTING: Internet-based survey of pediatric critical care community. INTERVENTIONS: None. RESULTS: A total of 159 responders completed the survey. Most respondents (92%) were fellowship-trained in pediatric critical care, with 9.9 +/- 6.5 yrs of experience. Many (85%) worked in the United States; 89% were in large tertiary care centers with residency or fellowship training programs. Most (65%) were aware of the adult randomized trials of therapeutic hypothermia, but only 9% (always) or 38% (sometimes) utilize this therapy. The most common reason to use hypothermia was likelihood of patient recovery, absence of life-limiting disease, and presence of coma for >/=1 hr after resuscitation. The majority of responders using therapeutic hypothermia cool their patients to 33-35 degrees C for a duration ranging from as short as 12 hrs to as long as 96 hrs; 91% do not actively rewarm the patient. A majority (81%) agree that a randomized, controlled trial of therapeutic hypothermia in children is ethical, and 95% would be willing to randomize their patients. Finally, 81% thought that therapeutic hypothermia should be studied in other ischemic insults and not just cardiac arrest. CONCLUSIONS: Despite widespread awareness of therapeutic hypothermia's beneficial effects after arrest, it is not widely used by pediatric critical care clinicians sampled in our survey. Among those using hypothermia, there is wide variation in methodology and end points of therapy. This seems to result from a lack of evidence, difficulty with the technique, and unavailability of explicit protocols. Pediatric studies are needed to assess the safety, feasibility, and effectiveness of therapeutic hypothermia after cardiac arrest and other causes of brain injury.

Attitude of Health Personnel↗
PubMed2006

Psychiatric nurses' perceptions of the constituents of the therapeutic relationship: a grounded theory study.

Psychiatric nursing is invariably linked with a therapeutic role; however, the question remains unanswered in relation to the extent psychiatric nurses perceive the importance of the constituents of the therapeutic relationship. The aim of this research is to ascertain the nature and comprehension psychiatric nurses assign the development of this therapeutic relationship. Grounded theory methodology was utilized to develop these conceptualizations to elicit a theory relating to what comprises the therapeutic relationship. Semi-structured depth interviews were conducted with 6 registered psychiatric nurses who have 2-10 years of experience. The main findings of the research related to how psychiatric nurses learn to form these relationships and what skills are utilized within the relationship. The research discovered that the therapeutic relationship is therapeutic, but the degree of positive change is difficult to measure. The results of the study indicate that the process of developing therapeutic relationships is a combination of a learned experience through the acquiring of interpersonal skills; however, these skills are redundant if the individual has not acquired sufficient life experience to intuitively appreciate the therapeutic aspect of the relationship.

Attitude of Health Personnel↗
PubMedDate not supplied

Optometric therapeutic competency standards 2000.

BACKGROUND: Competency standards for entry-level to the profession of optometry in Australia were first developed in 1993 and then revised in 1997. The competencies require that optometrists entering the profession have the skills to use ocular diagnostic drugs but did not consider the prescription of topical therapeutic ocular drugs by optometrists. Following the introduction of legislation in the Australian state of Victoria that permitted optometrists to be licensed by the relevant state registration board to prescribe topical therapeutic ocular medication, Optometrists Association Australia (OAA) was asked to develop therapeutic competency standards that could be used in the assessment of the suitability of optometrists for such licensing. METHODS: Expert members of the profession and representatives from optometry schools, registration boards in Australia and New Zealand, state divisions of OAA and the New Zealand Association of Optometrists (NZAO) were consulted in the process of developing these standards. RESULTS: Nine new performance criteria with associated indicators, within Units 3 and 5 of the revised entry-level standards, were developed. Additions were made to the indicators for 25 of the previously developed performance criteria (within all six original units of competency). The modified therapeutic competency standards were adopted on behalf of the profession by the National Council of OAA in March 2000. DISCUSSION: These therapeutic competency standards may be used as a basis for licensing authorities to develop an assessment process to determine suitability of optometrists for licensing to prescribe topical therapeutic ocular medications. At this stage, the therapeutic competencies cannot be regarded as entry-level competencies in Australia but as second-tier competencies. However, it is anticipated that the therapeutic competencies will come to be regarded as entry-level over the coming years.

Journal Article↗
PubMed2005

Low CD8 T-cell proliferative potential and high viral load limit the effectiveness of therapeutic vaccination.

Therapeutic vaccination has the potential to boost immune responses and enhance viral control during chronic infections. However, many therapeutic vaccination approaches have fallen short of expectations, and effective boosting of antiviral T-cell responses is not always observed. To examine these issues, we studied the impact of therapeutic vaccination, using a murine model of chronic infection with lymphocytic choriomeningitis virus (LCMV). Our results demonstrate that therapeutic vaccination using a recombinant vaccinia virus expressing the LCMV GP33 CD8 T-cell epitope can be effective at accelerating viral control. However, mice with lower viral loads at the time of vaccination responded better to therapeutic vaccination than did those with high viral loads. Also, the proliferative potential of GP33-specific CD8 T cells from chronically infected mice was substantially lower than that of GP33-specific memory CD8 T cells from mice with immunity to LCMV, suggesting that poor T-cell expansion may be an important reason for suboptimal responses to therapeutic vaccination. Thus, our results highlight the potential positive effects of therapeutic vaccination on viral control during chronic infection but also provide evidence that a high viral load at the time of vaccination and the low proliferative potential of responding T cells are likely to limit the effectiveness of therapeutic vaccination.

Animals↗
PubMed2026

Unlocking the potential of bacteriophage-based therapeutic gene delivery in hepatocellular carcinoma.

Liver cancer, mainly hepatocellular carcinoma (HCC), remains a global health burden marked by poor prognosis with limited therapeutic efficacy, and high recurrence rates. HCC remains one of the most lethal malignancies worldwide, with limited therapeutic options and high resistance to conventional treatments. Despite low therapeutic efficacy, molecular heterogeneity, treatment resistance and high recurrence rate, hepatocellular carcinoma (HCC) is still a significant health problem worldwide. These restrictions have stimulated the research of focused methods for delivering therapeutic genetic payload into cancer cells. Bacteriophages have been gaining growing attention as an emerging delivery platform due to their genetic versatility, ease of engineering, ability to be surface modified and payload targeted. In this narrative review, the therapeutic potential of engineered bacteriophages in the context of HCC therapy is critically analyzed focusing on phage display-mediated tumor targeting, phage-mediated intracellular gene delivery, TRAIL gene delivery, and CRISPR/Cas-based therapeutic strategies. It has been previously noted in the literature that phage display can be used to attach tumor-targeting ligands to the surface of a phage, which may aid in the recognition of receptors at the tumor site and promote targeted delivery to the receptor. Therapeutic application is stunted by inefficient trafficking to the cytosol, endosomal degradation, immune recognition and clearance, vector stability, manufacturing scalability and regulatory issues. In conclusion, engineered bacteriophages are a promising and versatile tool for targeted gene delivery in HCC but more mechanistic, preclinical and translational research is needed to prove their therapeutic effectiveness and clinical usefulness for this purpose.

Humans↗
PubMed2004

Strategies for targeting protein therapeutics to selected tissues and cells.

The advent of recombinant biotechnology and the recent sequencing of the human genome now allow for identification of scores of potential protein therapeutics along with the capacity to produce them in quantities and purities required for clinical application. Thus, clinical development of potential protein therapeutics has become as commonplace as development efforts of classical small molecule therapeutics. Whereas small molecule therapeutic lead candidates are identified through screens of large sets of possibilities, therapeutic protein candidates are defined by genetic information as a single composition (or a limited set of isoforms). Small molecule leads are identified through the combined assessment of desired selectivity, biodistribution and pharmacokinetic properties. In essence, these selection parameters emulate the actions of protein therapeutics that function as systemic hormones through their ability to target selective cells and tissues of the body via selective receptor interaction with minimal actions elsewhere. However, many, if not most, potential protein therapeutics do not normally circulate through the body to reach their target cell or tissue; rather, they are frequently synthesised at local sites, act at that site and are degraded without reaching appreciable systemic levels. Dose-limiting adverse events are associated with systemic administration of many of these proteins, restricting their clinical potential. This review examines current strategies to reduce these dose-limiting events by possibly focusing the delivery of potential protein therapeutics to discrete tissues and cells.

Animals↗
PubMed1998

The relationship between serum concentration and therapeutic effect of haloperidol in patients with acute schizophrenia.

Haloperidol is the most commonly used antipsychotic drug in the therapy of acute schizophrenia. Clinicians have been using therapeutic drug monitoring in an attempt to improve clinical application of this drug. The scale of interest in this area is emphasised by the large number of studies (about 50) concerning the serum concentration-therapeutic effect relationship (SCTER) of haloperidol, including 35 studies on patients with acute schizophrenia. However, conflicting results concerning the existence and position of a therapeutic window have emerged. This article aims to provide a comprehensive review of the study design of studies in patients with acute schizophrenia before the study data are used for decision-making. For this purpose, a reproducible system for the evaluation of studies in this special area, a so-called total study score (TSS), was developed on an empirical basis. Thus, insufficient study design was found to be a reason for negative results. On the other hand, in spite of a great variability, the majority of studies with good design provided evidence for a significant SCTER: a bisigmoidal dependence of clinical effect on haloperidol serum concentration. The therapeutic effects of haloperidol increase at low concentrations, and the concentration has a maximum effect at about 10 micrograms/L and again decreasing at higher concentrations. The data of 552 patients also fit to this model in a single scatter plot (pseudo-r2 = 0.076, p < 0.001). The position of the therapeutic window was determined at about 5.6 to 16.9 micrograms/L. Patients treated with serum concentrations within this optimal range had a significantly better response compared with outside this range (p < 0.001, Student t-test). Therefore, a quantitative synthesis of all available data by means of effect-size analysis provides a mean effect-size (g) = 0.499 +/- 0.182 (standard deviation) for the comparison of haloperidol-treatment with serum concentrations within versus outside the therapeutic window. Thus, because of this moderate positive effect, serum concentration assay of haloperidol is recommended for patients with acute schizophrenia in a therapeutic drug monitoring programme. The modalities of haloperidol therapeutic drug monitoring in clinical practice are discussed, e.g. patient selection, method and time for serum concentration measurement, influence of premedication and comedication, interpretation of results and dose adjustment. Clinical investigations into this subject should focus on covariates which are responsible for the variability of the SCTER. Serum concentration assay is advised for investigations of nonresponse to exclude patients with pseudo-drug resistance.

Acute Disease↗
PubMed2002

Comprehensive survey of the relationship between serum concentration and therapeutic effect of amitriptyline in depression.

The relationship between serum concentration (C(s)) of amitriptyline and its therapeutic effect in depression has been investigated frequently over the last 3 decades; however, the results were controversial and no consensus was reached. Therefore, we have performed a comprehensive survey and meta-analysis of the subject. All relevant literature was included, and the design of studies on the serum concentration-therapeutic effect relationship (SCTER) of amitriptyline was evaluated. Pooled original data from SCTER studies with adequate design were analysed by various statistical methods: regression analysis of therapeutic effect and C(s); comparison of the mean therapeutic effect in various ranges of C(s); dichotomisation of outcome and analysis according to sensitivity of receiver operation curves; frequency of responders and nonresponders in ranges determined by points of sensitivity; analysis of the distribution of C(s) in responders and nonresponders; logistic regression of responders and nonresponders with C(s) and other independent variables; calculation of effect size (g) and mean effect size (g(m)). Forty-five SCTER studies of amitriptyline were identified, and 27 studies met the minimum criteria of adequate study design. Inadequate study design predicted the finding of no SCTER. Analysis of the pooled data from studies with adequate design confirmed a therapeutic window of the sum of C(s) of amitriptyline and its active metabolite nortriptyline of about 80 to 200 microg/L. A moderate and significant positive g(m) (0.538, 95% confidence interval 0.167 to 0.909) was calculated for treatment with C(s) within the therapeutic window in comparison with treatment with C(s) outside the therapeutic window (19 studies with adequate design and original data available, n = 583). In conclusion, the evidence for a biphasic SCTER of amitriptyline in depression is considerably improved, and the results may help to find a consensus in the future. However, the clinical benefit of therapeutic drug monitoring of amitriptyline can only be demonstrated in a controlled and randomised study. Furthermore, the results provide further evidence that antidepressants at optimum C(s) are superior to placebo in the treatment of depression.

Amitriptyline↗
PubMed2005

Pharmacokinetic and pharmacodynamic considerations in the development of therapeutic proteins.

With an increasing number of therapeutic proteins moving into preclinical and clinical development, pharmacokinetic factors play an important role in the development of these macromolecules. It is also important that the pharmacokinetic evaluation of these compounds be done as accurately as possible. For macromolecules, evaluation of pharmacokinetic parameters is often complicated by a number of factors. Bioanalytical methods are essential for any pharmacokinetic study, but for many therapeutic proteins the immunoassay and bioassay methodologies are often nonspecific and sometimes the estimation of pharmacokinetic parameters becomes assay dependent. In vivo binding proteins, metabolites and antibody formation may also interfere with bioanalytical methodologies and thus may have significant impact on the pharmacokinetics of therapeutic proteins. There are also difficulties in identifying and quantifying metabolites as well as the binding of therapeutic proteins to endogenous proteins. Some macromolecules exhibit species specificity that complicates the preclinical pharmacological and toxicological evaluation of these compounds. Antibody formation is a particular problem in the preclinical evaluation of therapeutic proteins. Changes in structure or sequence of protein molecules (glycosylation or pegylation) may cause changes in the pharmacokinetics of these compounds. The size of therapeutic proteins may become a hindrance for absorption. Low absorption of intact molecules across biological membranes frequently occurs. Other factors that may affect the pharmacokinetics of a therapeutic protein are immunogenicity, presence of endogenous protein, time of drug administration, and rate and site of drug delivery. The relationship between pharmacokinetics and pharmacodynamics of therapeutic proteins is complex and in most cases is unclear. In many cases the mechanism and site of action are unknown for these compounds.

Absorption↗
PubMed2002

Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma.

OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm. Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size. CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.

Adenoma↗
PubMed1999

Effect of docetaxel on the therapeutic ratio of fractionated radiotherapy in vivo.

The aim of this investigation was to determine whether docetaxel increases the therapeutic ratio of fractionated radiotherapy in vivo. Two tumor types were chosen based on their sensitivity to docetaxel as a single agent: (a) docetaxel-sensitive MCa-4 mammary adenocarcinoma, which responds to docetaxel by G2-M-phase cell cycle arrest, apoptosis, and subsequent reoxygenation of surviving tumor cells; and (b) docetaxel-resistant SCC-VII squamous cell carcinoma, which responds to docetaxel treatment only by G2-M-phase arrest. Response of the normal jejunal mucosa in mice was compared to the response of both tumor types to confirm therapeutic gain. We conducted micromorphometric analysis of tumor cell mitosis, assayed apoptosis by its histological appearance in tissue sections, and determined tumor response by tumor growth delay. Normal tissue response of the jejunum was assayed by micromorphometric analysis of mitotic and apoptotic indices, and clonal crypt stem cell survival was measured using the microcolony assay. Two clinically relevant treatment schedules were tested for both antitumor efficacy and normal tissue toxicity: (a) a single bolus of docetaxel (33 mg/kg i.v.) 24 h before five daily fractions of radiation; and (b) daily administration of docetaxel (8 mg/kg i.v.) with radiation delivered at the peak of mitotic arrest (9 h for MCa-4 and 6 h for SCC-VII tumors). The best therapeutic gain for docetaxel-sensitive MCa-4 was achieved with a single bolus of drug 24 h before the start of fractionated radiotherapy (therapeutic gain = 2.04). This schedule takes advantage of reoxygenation of hypoxic tumor cells during the interval between drug treatment and radiation delivery. The best therapeutic gain for docetaxel-resistant SCC-VII was achieved with intermittent multiple doses of docetaxel given during the course of fractionated radiotherapy. This schedule maximized the exposure of cells to radiation while they were arrested by docetaxel in the radiosensitive G2-M phases of the cell cycle (enhancement factor = 2.0). Final therapeutic gain was reduced to 1.59 because of increased normal tissue toxicity in mice treated with multiple intermittent doses of docetaxel in combination with fractionated radiotherapy. Thus, docetaxel greatly enhanced tumor response to fractionated radiotherapy, but the magnitude of therapeutic efficacy depended on drug-radiation scheduling. The greatest therapeutic gain in the treatment of docetaxel-sensitive tumors was achieved by a single large dose of docetaxel administered 1 day before the initiation of fractionated radiotherapy and in the treatment of docetaxel-resistant tumors by daily concomitant docetaxel-radiation treatments.

Adenocarcinoma↗
PubMed2003

Patients' ranking of therapeutic factors in group analysis.

The aim of this research is to assess which therapeutic factors are of greatest importance to patients in group analytic psychotherapy, and whether the patients' characteristics and the phase of the group process influenced their evaluation of therapeutic factors. The Yalom's group therapeutic factors questionnaire was filled out by 66 patients, members of small groups conducted according to group analytic principles. The average scores for each therapeutic factor were subsequently ranked by importance to the patients and related to their age, sex, education, previous psychotherapeutic experience and phase of group process. Self-understanding was the highest-ranking therapeutic factor for the patients (average score 21.32 +/- 0.04 out of 25 maximum), whereas identification was the lowest ranking factor (15.88 +/- 0.06 in average). Group therapeutic factors were scored higher by women, patients up to 30 years of age, high-school graduates, and those with previous psychotherapeutic experience. Self-understanding seems to be the most important therapeutic factor in group analysis, emphasizing the importance of appropriate selection of patients for group analysis in order to utilize therapeutic factors the best.

Adult↗
PubMed2004

[Treatment of hepatocellular carcinoma with a novel gene-viral therapeutic system CNHK300-murine endostatin].

OBJECTIVE: To investigate the anti-tumor effects of a novel gene-viral therapeutic system CNHK300-murine endostatin (CNHK300-mE) in hepatocellular carcinoma (HCC). METHODS: A novel gene-viral therapeutic system named CNHK300-mE was constructed by employing the human telomerase reverse transcriptase (hTERT) promoter to drive the expression of adenovirus E1A gene and cloning the therapeutic gene murine endostatin (mE) into the adenovirus genome. Hepatocellular cells of the HepGII and Hep3B lines and normal fibroblasts of the MRC-5 line were cultured and infected with the viruses CNHK300-mE, ONYX-015, replicative adenovirus without therapeutic gene, and Ad-mE, non-replicative adenovirus with the same therapeutic gene. Ninety-six hours after the infection, tissue culture infectious dose 50 method was used to detect the titer of virus in the supernatants. MTT method was used to examine the cytolytic capability. The expression of E1A and mE were examined by Western blotting. ELISA assay was used to detect the transgene expression of mouse endostatin. Healthy nude Balb/c mice were injected with hepatic cancer cells of the SMMC 7221 line. Forty mice with tumors 5 approximately 8 mm in diameter were randomly divided into 4 groups of 20 mice: CNHK300-mE group (CNHK300-mE was injected into the tumor once every other day for 5 times), Ad-mE group (Ad-mE was injected), ONYX-015group (ONYX-015 was injected), and control group (diluent of virus was injected). 3, 7, 14, 21, and 28 days after the initial injection the size of tumor was examined. 48 hours after the finish of the whole course of treatment, the mice were killed. ELISA was used to detect the expression of mE in blood. The growth of tumor was examined by HE staining, The angiogenesis in the tumor was observed by immunohistochemistry with von Willebrand factor and The proliferation of transplanted tumor was observed by immunohistochemistry with adenovirus envelop protein hexon. RESULTS: Ninety-six hours after the infection of the cells by CNHK300-mE virus was replicated by 6329 +/- 1830 and 25 136 +/- 6890 times in the HepGII and Hep3B cells respectively, 3296 and 12 824 times higher than in the MRC-5 cells respectively. The replication multiples of ONYX-015 virus in the HepGII and Hep3B cells were 2040 +/- 450 and 3980 +/- 740 times respectively, both significantly lower than those of CNHK300-mE virus (both P < 0.05). However, no remarkable replication of Ad-mE virus was seen in the Western blotting showed the expression of therapeutic gene mE in HepGII and Hep3B cells infected with CNHK300-mE on Ad-mE. Hep3B cells, the band of CNHK300-mE being thicker than that of Ad-mE and the band of Ad-mE being similar to that of CNHK300-mE in the MRC-5 cells. ELISA showed that the expression of mE protein in the HepGII cells infected by CNHK300-mE virus increased time-dependently during the period of 7 days after virus infection, significantly higher than the expression in the HepGII cells infected by Ad-mE virus (P < 0.05). The tumors of the CNHK300-mE virus-infected mice were significantly smaller than those of the Ad-mE and ONYX-015-infected mice (both P < 0.01). ELISA showed that the mE protein content in the blood of the CNHK300mE-infected mice was significantly higher than that of the Ad-mE group (P < 0.05). Hexon immunohistochemistry showed patchy and diffuse positive staining related to apoptosis and necrosis of tumor cells in the transplanted tumors of the CNHK300-mE virus-infected mice, however, only sporadic positive staining was seen in the Ad-mE virus-infected mice. CONCLUSION: Being capable of specifically replicating in the telomerase-positive HCC cells and mediating effective expression of therapeutic gene in vitro and in vivo, the novel gene-viral therapeutic system CNHK300-mE holds potential for treatment of HCC.

Adenoviridae↗