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At least 379 records · Page 21Linked to original sources
PubMed2003

Effects of therapeutic doses of 131I in thyroid papillary carcinoma patients with elevated thyroglobulin level and negative 131I whole-body scan: comparative study.

OBJECTIVE: Previous studies have shown a high rate of visualization of uptake and a decrease in serum thyroglobulin (Tg) after therapeutic doses of 131I in well-differentiated thyroid cancer patients with elevated thyroglobulinaemia but negative diagnostic 131I whole-body scan (DxWBS), but its therapeutic effect remains controversial. We evaluate the effect of therapeutic doses of 131I in patients with elevated thyroglobulin level but negative DxWBS. DESIGN: Among papillary thyroid carcinoma patients who underwent total or near-total thyroidectomy and remnant ablation with radioiodine during 1996 to 2000 in our hospital, the patients who showed elevated serum Tg levels and no abnormal uptake in DxWBS were selected. The selection for treatment or no treatment was decided according to the preference of the patients, considering side-effects of therapeutic doses of 131I, and the patients were thereafter studied retrospectively. PATIENTS: Sixty papillary thyroid carcinoma patients with elevated thyroglobulinaemia but negative DxWBS were included. Twenty-eight patients were treated, and 32 were untreated. MEASUREMENTS: We compared serum Tg levels measured at less than 3 months before the administration of therapeutic doses of 131I or DxWBS with the levels at 6-12 months after administration between two groups. Comparable data on changes in serum Tg levels during TSH suppression (Tg-on) and those in hypothyroid phase (Tg-off) were available in 25 and 49 patients, respectively. RESULTS: Percentage decreases in both Tg-on and Tg-off levels of the treated group [41.2 (10.1-94.1)% and 37.0 (-176.6-88.4)%, respectively] were significantly higher than those of the untreated group [-43.6 (-180.1-7.3)% and -66.6 (-10644.2-39.1)%, respectively] (P < 0.001). The treated patients were followed-up for 23.8 +/- 19.6 months after the administration of therapeutic doses of 131I. In four cases, serum Tg levels converted to negative (< 1.0 ng/ml) both on and off T4 15-22 months after the administration of therapeutic doses of 131I, and negative serum Tg levels persisted for 24-70 months. However, negative conversion of elevated serum Tg levels was not observed in any of the untreated group. Post-treatment WBS revealed pathologic uptake in 12 of 28 cases (42.9%). CONCLUSIONS: This study revealed that the administration of therapeutic doses of 131I has a therapeutic effect, at least for palliation in short-term observation, considering the serum Tg level as an index of tumour burden, and that it can disclose previously undiagnosed lesion in some patients with differentiated thyroid cancer who show elevated thyroglobulin level but negative diagnostic 131I whole-body scan.

Adolescent↗
PubMed2004

Insulin inhalation--Pfizer/Nektar Therapeutics: HMR 4006, inhaled PEG-insulin--Nektar, PEGylated insulin--Nektar.

Nektar Therapeutics (formerly Inhale Therapeutic Systems) has developed a pulmonary drug delivery system for insulin [HMR 4006, Exubera]. The rationale behind developing a pulmonary drug delivery system is to ensure that insulin powder is delivered deep into the lungs, where it is easily absorbed into the bloodstream, in a hand-held inhalation device. The device converts the insulin powder particles into an aerosol cloud for the patient to inhale. No propellants are used. The inhaler requires no power source and the clear chamber ensures that the patient knows immediately when all the insulin has been inhaled. Nektar Therapeutics, developers of the inhalation device and formulation process, has licensed the system to Pfizer. Under the terms of the agreement, Pfizer will lead the clinical development of inhaled insulin, while working with Nektar Therapeutics to develop the technology required for packaging the product. Pfizer has an agreement with Hoechst Marion Roussel (now Aventis Pharma) for developing, manufacturing and promoting inhaled insulin. Under the terms of the collaboration, Aventis Pharma will supply recombinant insulin to Nektar Therapeutics to process it into dry powder for incorporation into the inhaler device. Nektar Therapeutics will receive royalties on sales of inhaled insulin marketed by Pfizer and Aventis Pharma, and milestone payments and research support from Pfizer. Aventis Pharma's codename for the product is HMR 4006.Profil, a CRO in Germany, is cooperating with Pfizer/Aventis Pharma in the development of inhaled insulin. In March 2004, Pfizer and Aventis announced that the European Medicines Evaluation Agency (EMEA) accepted the filing of the MAA for inhaled insulin (Exubera) for the treatment of type 1 and type 2 diabetes mellitus. The two companies are working with the US FDA to determine the timing for the submission of the NDA in the US. Pfizer completed five pivotal phase III clinical trials with inhaled insulin in patients with type 1 and type 2 diabetes mellitus in 120 centres worldwide, and will use a fourth prototype inhaler device that is half the size of the first prototype, and has reduced manufacturing costs. Pfizer and its partner, Aventis Pharma, are conducting additional long-term pulmonary safety data studies in patients with type 1 and type 2 diabetes. Pfizer is also conducting phase III clinical trials with inhaled insulin in paediatric patients aged 6-17 years. Nektar Therapeutics is using its Advanced PEGylation technology to develop a dry powder-inhaled polyethylene glycol (PEG) formulation for delivering peptides efficiently across the lungs and to promote prolonged serum concentration of the peptide. PEG is a neutral, water-soluble, nontoxic polymer comprising any number of repeating units of ethylene oxide. PEGylation is designed to increase the size of the active molecule and ultimately improve drug performance by optimising pharmacokinetics, increasing bioavailability, and decreasing immunogenicity and dosing frequency. The investigation has begun with inhaled, long-acting (PEGylated) insulin [inhaled PEG-insulin, PEGylated insulin--Nektar], and is funded by Pfizer. Preclinical results of a dry powder formulation of inhaled PEG-insulin presented at the 63rd Scientific Sessions of the American Diabetes Association (ADA-2003) [June 2003, New Orleans, LA, USA] demonstrated prolonged systemic activity of insulin in dogs. Nektar Therapeutics was granted US patent 5,997,848 on a method for delivering inhalable insulin. The patent covers a method for delivering of 0.5-15 mg of aerosol dry powder insulin per dosing session in 1-4 individual dosages into the deep lung for systemic absorption. The patent does not specify the formulation of insulin or aerosol delivery device. Nektar Therapeutics estimated in June 2002 that Exubera could earn the company potential revenues of >200 million US dollars.

Administration, Inhalation↗
PubMed2000

Linking evidence-based medicine therapeutic summary measures to clinical decision analysis.

OBJECTIVE: Evidence-based medicine (EBM) seeks to improve clinical practice by evaluating the quality of clinical evidence and ensuring that only the "best" evidence from clinical research is used in the management of individual patients. EBM has contributed to our understanding of the meaning of the benefit and harm of treatment as reported in the literature, and it is often promoted as an aid to clinical decision making. However, EBM therapeutic summary measures reflect only a single dimension of clinical decision making. The purpose of this work is to show how EBM therapeutic summary measures can be effectively incorporated into medical decision making. DESIGN: The effective application of the therapeutic summary measures advocated by EBM requires their integration into the framework of clinical decision analysis. Clinical decision analysis involves not only the identification and specification of the probabilities of clinical events but also the assessment of their relative values or utilities. We present here several analytic models for the integration of EBM therapeutic summary measures within the framework of clinical decision analysis. MAIN RESULTS: As expected, our analysis demonstrated that treatment should never be administered if its harm is greater than its efficacy, which is generally expressed as relative risk reduction. Likewise, a diagnostic test should never be ordered if the therapeutic harm is greater than the therapeutic efficacy. Intervention is always favored if the number needed to treat to avoid one adverse outcome (NNT) is smaller than the number needed to treat to harm one individual (NNH). When faced with a choice between two therapeutic options, the action threshold above which an intervention is favored can be expressed in terms of the harm inflicted (H) as H x NNT or NNT/NNH. If a patient's preferences are taken into account as relative value judgments (RV) of adverse events relative to that of therapeutic events, the action threshold is defined as NNT x (RV/NNH). CONCLUSIONS: In the setting of clinical decision making, EBM summary measures derived from population studies can be effectively used to define diagnostic and therapeutic action thresholds that may help in the management of individual patients.

Aged↗
PubMed2003

[Importance of the Therapeutic Products Act for the ENT practitioner].

The Therapeutic Products Act controls therapeutic products and their fields of application, and classifies them legally. The present regulations on therapeutic products are based on a fundamental concept comprising basic demands, harmonized standards, agreement of the product attributes with the basic demands, and assessment of conformity. Therapeutic products (among which in vitro diagnostics are counted) must comply with definite regulations and are separated from medicines by their mode of action. In addition, therapeutic products must be subject to critical testing. The establishment, management, and use of therapeutic products are, with few exceptions, governed by the Regulations for the Use of Therapeutic Products. To avoid possible risks involved in the application of therapeutic products, a well-functioning system of registration is required, controlled by the Regulations on Therapeutic Products Safety.

Device Approval↗
PubMed2002

Nonthermal effects of therapeutic ultrasound: the frequency resonance hypothesis.

OBJECTIVE: To present the frequency resonance hypothesis, a possible mechanical mechanism by which treatment with non-thermal levels of ultrasound stimulates therapeutic effects. The review encompasses a 4-decade history but focuses on recent reports describing the effects of nonthermal therapeutic levels of ultrasound at the cellular and molecular levels. DATA SOURCES: A search of MEDLINE from 1965 through 2000 using the terms ultrasound and therapeutic ultrasound. DATA SYNTHESIS: The literature provides a number of examples in which exposure of cells to therapeutic ultrasound under nonthermal conditions modified cellular functions. Nonthermal levels of ultrasound are reported to modulate membrane properties, alter cellular proliferation, and produce increases in proteins associated with inflammation and injury repair. Combined, these data suggest that nonthermal effects of therapeutic ultrasound can modify the inflammatory response. CONCLUSIONS: The concept of the absorption of ultrasonic energy by enzymatic proteins leading to changes in the enzymes activity is not novel. However, recent reports demonstrating that ultrasound affects enzyme activity and possibly gene regulation provide sufficient data to present a probable molecular mechanism of ultrasound's nonthermal therapeutic action. The frequency resonance hypothesis describes 2 possible biological mechanisms that may alter protein function as a result of the absorption of ultrasonic energy. First, absorption of mechanical energy by a protein may produce a transient conformational shift (modifying the 3-dimensional structure) and alter the protein's functional activity. Second, the resonance or shearing properties of the wave (or both) may dissociate a multimolecular complex, thereby disrupting the complex's function. This review focuses on recent studies that have reported cellular and molecular effects of therapeutic ultrasound and presents a mechanical mechanism that may lead to a better understanding of how the nonthermal effects of ultrasound may be therapeutic. Moreover, a better understanding of ultrasound's mechanical mechanism could lead to a better understanding of how and when ultrasound should be employed as a therapeutic modality.

Journal Article↗
PubMed1998

Population effects of preventive and therapeutic HIV vaccines in early- and late-stage epidemics.

OBJECTIVE: To evaluate the population effects of potential preventive and therapeutic vaccines in early- and late-stage epidemics in a population of homosexual men. METHODS: An epidemic model was used that simulated the course of the epidemic for a population of homosexual men in San Francisco, California. Vaccine programs were evaluated by the number of cases of HIV averted, the effect on the prevalence of HIV, and by the gain in quality-adjusted life years (QALY) for the total population. RESULTS: In the model, a preventive vaccine prevented 3877 cases of HIV infection during a 20-year period, reduced the projected prevalence of HIV infection from 12 to 7% in a late-stage epidemic, and gained 15,908 QALY. A therapeutic vaccine that did not affect the infectivity of vaccine recipients increased the number of cases of HIV infection by 210, resulted in a slight increase in the prevalence of HIV infection from 12 to 15% in a late-stage epidemic, and gained 8854 QALY. If therapeutic vaccines reduced infectivity, their use could produce net gains of QALY in the population that were similar to gains from the use of preventive vaccines. In an early-stage epidemic, the advantage of a preventive vaccine program relative to a therapeutic vaccine program was markedly enhanced. CONCLUSIONS: Both preventive and therapeutic vaccine programs provided substantial benefit, but their relative merit depended on which outcome measures were assessed. Evaluation of HIV vaccine programs based solely on cases averted or on prevalence of HIV in the population underestimates the benefit associated with therapeutic vaccine programs. The effect of a therapeutic HIV vaccine on the epidemic outcomes depended markedly on whether the therapeutic vaccine reduced the infectivity of the vaccine recipient. The relative merits of preventive and therapeutic vaccines depend on the stage of the epidemic. Field vaccine trials should evaluate correlates of infectivity, such as HIV viral load. HIV vaccine implementation strategies should be tailored to the dynamics of the epidemic in specific populations.

AIDS Vaccines↗
PubMed2005

Therapeutic optimism in the consent forms of phase 1 gene transfer trials: an empirical analysis.

BACKGROUND: "Therapeutic misconception" arises when human subjects interpret a clinical trial as aimed primarily at therapy rather than producing knowledge. Therapeutic misconceptions may be more prevalent in trials enrolling gravely ill subjects or involving novel and well publicized investigational agents. OBJECTIVE: To examine the extent to which investigators express therapeutic optimism in phase 1 human gene transfer consent documents, whether highly active gene transfer researchers are more prone to expressing therapeutic optimism, and whether consent forms have grown more optimistic in their descriptions of personal benefit over the last decade. DESIGN: Content analysis was performed on 277 consent documents to measure the number of sentences describing possibility of benefit, terminology used for experimental agents, the proportion of statements describing personal versus societal benefits, and whether investigators attempted to thwart therapeutic misconceptions. RESULTS: Consent forms generally used therapeutic terminology to describe study agents, devoted more sentences to describing possible personal benefits than to describing benefits to society, and infrequently explained that a particular benefit was unlikely. Consent documents used by highly active gene transfer researchers tended to portray significantly greater optimism about personal benefit than less active investigators, though they were also significantly more cautious with agent terminology. Finally, therapeutic optimism expressed in consent forms has declined over the past decade. CONCLUSIONS: Consent documents used in phase 1 gene transfer trials, although increasingly attentive to possible therapeutic misconceptions, are inappropriately optimistic about direct benefits of trial participation. Such optimism is expressed more emphatically in trials involving highly active gene transfer researchers as principal investigators.

Clinical Trials, Phase I as Topic↗
PubMed1990

Therapeutic inequivalence.

Therapeutic inequivalence may be defined as the absence of therapeutic equivalence when equivalence is expected. Generic drugs are regulated in the USA as follows: drugs which are copies of pre-1938 innovator drugs have no requirement for approval before marketing, whereas a major requirement for regulatory approval with generics of post-1938 innovator drugs is that their bioequivalence with the innovator drug must be demonstrated. Specifically, the generic drug is considered bioequivalent if its rate and extent of absorption are not significantly different (+/- 20%) from those of the innovator drug when administered under similar experimental conditions. In terms of risk-benefit assessment, the generic should be therapeutically equivalent to the innovator but less expensive. Therefore, the aim of generic drug regulation should be to minimise therapeutic inequivalence at a cost that does not obviate the economic benefits of generics. Regardless of the safety considerations with the innovator drug, there is always a small but finite additional risk of therapeutic inequivalence when switching from innovator to generic, or from one generic to another. To date, there is no evidence of therapeutic inequivalence in a properly manufactured generic drug which has been approved as bioequivalent by the FDA. Therapeutic inequivalence is more easily detectable in institutions than by individual physicians who may ascribe the symptoms of therapeutic failure to a worsening of the underlying disease of the patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Legislation, Drug↗
PubMed1997

Swimming against the tide? A review of the therapeutic community.

OBJECTIVE: The therapeutic community is an established psychiatric treatment method which may be in decline. This paper reviews the nature of inpatient therapeutic community treatment, and re-evaluates its role. METHOD: The principles and practice of such treatment are summarised, with a focus on the functions of staff. RESULTS: The inpatient therapeutic community is conceptualised as combining sociotherapeutic treatment, psychotherapeutic treatment, and the advantages of the inpatient setting. This unique treatment environment allows for therapeutic regression while mitigating against anti-therapeutic behavioural regression. Research evidence supports the efficacy of therapeutic community treatment for patients with borderline personality disorder. CONCLUSION: Further research is needed to assess its efficacy for other diagnostic groups. This intensive treatment approach may be most appropriate for patients who have proved treatment resistant by other means. Possible reasons for the marginalization of therapeutic community treatment are considered. Access to quality inpatient therapeutic community treatment is essential in the provision of a comprehensive psychiatric service.

Borderline Personality Disorder↗
PubMed1999

An integrative review and meta-analysis of therapeutic touch research.

OBJECTIVE: To perform an integrative research review and meta-analysis of therapeutic touch research. DATA SOURCES: Bibliography maintained by the Nurse Healers-Professional Associates International; MEDLINE, CINAHL, and Psylit databases; dissertations and master's theses. STUDY SELECTION: Thirty-eight research articles were included in the analysis. All dissertations and research articles were analyzed. DATA EXTRACTION: Data on 32 substantive characteristics of the sample, the therapeutic touch procedure, and the article/dissertation were extracted following Moody's method for an integrative research review. The meta-analysis used studies that reported means and standard deviations of the treatment and control groups. DATA SYNTHESIS: The research questions were as follows: (1) What are the substantive characteristics of the sample, the therapeutic touch practice, and the article/dissertation in research studies from 1975 to 1997? (2) What does the research demonstrate regarding the efficacy of therapeutic touch as an intervention? (3) Based on the results of the review and meta-analysis, what are the gaps, trends, and outcomes of the therapeutic touch research studies? CONCLUSIONS: The review demonstrated that there are many approaches to therapeutic touch research, samples are described incompletely, and the therapeutic touch practices vary in the studies. Most of the studies supported hypotheses regarding the efficacy of therapeutic touch, though a number had mixed or negative results. A meta-analysis was performed on 13 studies. The average effect size in these studies was .39, which is described as moderate. Gaps, trends, and outcomes were identified and discussed.

Adult↗
PubMed2000

Massage therapy and therapeutic touch in children: state of the science.

OBJECTIVE: To review and critique the research on the effect of massage therapy and therapeutic touch in children, and to describe clinical implications and make suggestions for future study. DATA SOURCES: Studies were obtained through online computer searches of CINAHL, MEDLINE, PsychInfo, and SocioFile. Key words used were tactile, kinesthetic, massage therapy, touch, therapeutic touch, infants, and children. STUDY SELECTION, DATA EXTRACTION, AND SYNTHESIS: Fourteen massage therapy studies were selected because they met the following 3 criteria: investigated massage therapy in children; were published in refereed nursing, allied health, or infant and child development journals between 1969 and 1999; and were quantitative in nature. Studies were divided according to developmental age for analysis: neonates, preschool, and older children. Five therapeutic touch studies, 3 quantitative and 2 qualitative, were selected because they were the only empirical reports about the effect of therapeutic touch in children to date. In addition to critiques, the therapeutic touch studies were examined for the following 10 characteristics: study purpose/hypotheses, background/literature review, sample selection method, study design/random assignment, independent variable/length of treatment/control and confounders, dependent variables/measurements, outcomes, study limitations, and implications for future research. CONCLUSIONS: More research exists to support the use of massage therapy than therapeutic touch in children. A set of common findings across 2 decades of study suggests that massage therapy may be useful in the care of infants and children. Because massage therapy and therapeutic touch seem to elicit similar parasympathetic effects, therapeutic touch may be useful. There is insufficient evidence, however, to recommend its use in children without qualifications.

Adolescent↗
PubMed2005

Patterns of therapeutic prescription medication category use among community-dwelling homebound older adults.

PURPOSE: The measurement of prescription medication use is usually through a simple count of medications, which tends to ignore therapeutic categories. This research investigated prescription medication use among homebound older adults, by documenting the therapeutic prescription medication categories used by these individuals and identifying the factors associated with use of multiple therapeutic categories. METHODS: Baseline Nutrition and Function Study (2000-2001) data from 326 homebound older persons who completed the medication review component (visual inspection of medications) of the baseline in-home interview and used > or =1 prescribed medication were included in this analysis. RESULTS: More than 40% (n = 133) regularly took medications from three to four different therapeutic categories and 31.6% (n = 103) used > or =5 different therapeutic categories. The use of respiratory medications declined with increasing age, and more women than men used diuretic and thyroid replacement medications. Independent of other factors, increased use of multiple therapeutic categories was associated with sociodemographic characteristics (gender, age, living arrangement, marital status and medication coverage), medical conditions (diabetes, heart problems and lung disease) and inability to self-manage medications. CONCLUSIONS: Our findings suggest that individual characteristics and medical conditions may help identify homebound elders at high risk for using prescription medications from an increased number of different therapeutic categories. This observation may help clinicians and community-based providers of services to older persons to be aware of differences in therapeutic medication use within an older population, and how patterns of use may alter service needs.

Age Factors↗
PubMed1995

Immunological detection of Clostridium botulinum toxin type A in therapeutic preparations.

The potent neurotoxins produced by strains of Clostridium botulinum act by blocking the release of acetylcholine from peripheral nerve junctions. This specific action of the botulinum neurotoxins is now being exploited therapeutically to treat a variety of conditions involving involuntary muscle spasms. We aimed to develop a sensitive and specific enzyme-linked immunosorbent assay (ELISA) which may be used in parallel with the currently accepted mouse bioassay test for the determination of botulinum neurotoxin type A in therapeutic preparations. High titre polyclonal antitoxins and their biotin derivatives, highly labelled horseradish peroxidase (HRP)-antibody conjugates, and streptavidin-biotin-HRP complexes were prepared and used in a sandwich ELISA for the detection of pure neurotoxin and neurotoxin in therapeutic material. The ELISA utilized either a monoclonal or polyclonal antibody as capture agent and HRP-labelled IgG or F(ab')2 fragment as second antibody. The limit of detection was 4-8 pg of purified toxin/ml (gcv < 13%), equivalent to 1-2 mouse bioassay units/ml. The assay was used to evaluate therapeutic preparations and the results compared with the mouse bioassay. The lower limit of detection for a therapeutic preparation of BoTxA was 2-5 mouse bioassay units/ml. Although across different manufacturers and bulk products there was no correlation between immunologically detected neurotoxin and its biological activity in different therapeutic preparations (r = -0.44, p = 0.34, n = 8), the assay could be used to quantify neurotoxin in therapeutic preparations derived from the same bulk concentrate and manufacturer. The assay is relatively simple, and may be readily adapted to routine monitoring of BoTxA content in therapeutic preparations.

Antibodies↗
PubMed2004

A prospective trial that demonstrates that dalteparin requirements increase in pregnancy to maintain therapeutic levels of anticoagulation.

OBJECTIVE: The purpose of this study was to determine whether standard therapeutic doses of dalteparin maintain peak therapeutic levels of anticoagulation during pregnancy. STUDY DESIGN: This was a prospective trial in which 13 pregnancies that required therapeutic anticoagulation were treated with dalteparin 100 U/kg every 12 hours; peak and trough (predose) low molecular weight heparin (anti-Xa activity) levels were monitored every 2 weeks. Dosage adjustments were made to maintain peak anti-Xa activity between 0.5 and 1.0 IU/ml. Bone density and bone turnover markers were measured. RESULTS: A total of 250 peak and trough low-molecular-weight heparin (LMWH) levels were obtained. Eighty-five percent of pregnancies (11/13) required an upward dosage adjustment. Trough levels were in the therapeutic range only 9% of the time, despite the maintenance of therapeutic peak levels. Bone resorption markers and density were unchanged in singleton pregnancies. CONCLUSION: Dalteparin dosing, based on weight alone, every 12 hours is inadequate to maintain most pregnant women in the therapeutic range throughout pregnancy as measured by anti-Xa activity. Trough levels are rarely in the therapeutic range, despite maintenance of therapeutic peak levels. These notable changes in low molecular weight heparin peak may explain reported failures in pregnancy.

Abortion, Spontaneous↗
PubMed2005

The fast is positive, now what? Derivation of a clinical decision rule to determine the need for therapeutic laparotomy in adults with blunt torso trauma and a positive trauma ultrasound.

INTRODUCTION: The object of this study was to derive a clinical decision rule for therapeutic laparotomy among adult blunt trauma patients with a positive abdominal ultrasound for trauma (FAST) examination. METHODS: We retrospectively reviewed the trauma registry and medical records of all critical trauma patients who underwent a FAST examination in the emergency department (ED) in a university Level I trauma center over a 3-year period. Blunt trauma patients aged >16 years who had a positive FAST examination (defined as the presence of intraperitoneal fluid) were eligible. We selected seven clinical and ultrasound variables available during ED resuscitation for analysis: age, presence of an episode of hypotension (systolic blood pressure <90 torr in the ED), presence of abdominal tenderness, chest injury, pelvic fracture, femur fracture, and FAST fluid location (right upper quadrant [RUQ] only; RUQ plus other location; other location only). The primary outcome variable was whether a laparotomy was performed and whether this laparotomy was needed to provide the definitive surgical intervention ("therapeutic laparotomy"). We analyzed the variables using binary recursive partitioning analysis to create a decision rule. RESULTS: There were 2336 FAST examinations performed during the study period, resulting in 230 (9.8%) positive examinations in patients meeting inclusion criteria. There were 135 patients who had therapeutic laparotomies and 95 who did not need laparotomy. The groups were similar in baseline characteristics. In the recursive partitioning analysis, the first node in the decision tree was the presence of fluid in the RUQ. Of the 144 patients with RUQ fluid, 105 (73%, 95% confidence interval [CI] 64%-80%) required therapeutic laparotomy. Of the 86 patients without RUQ fluid, 30 (35%, 95% CI 25%-46%) nevertheless required therapeutic laparotomies, and the variables blood pressure, femur fracture, abdominal tenderness, and age further divided these patient into high- and low-risk groups. Of the 12 patients without RUQ fluid who had normal blood pressures, no femur fractures, no abdominal tenderness, and were aged 60 years and younger, none (95% CI 0%-22%) required therapeutic laparotomy. In conclusion, given a positive FAST examination, the presence of fluid in the RUQ is an important predictor of the need for therapeutic laparotomy. CONCLUSION: In the absence of fluid in the RUQ, there are other clinical variables that may allow for the development of a clinical decision rule regarding the need for therapeutic laparotomy.

Abdominal Injuries↗
PubMed2004

Therapeutic HER2/Neu DNA vaccine inhibits mouse tumor naturally overexpressing endogenous neu.

The therapeutic efficacy of HER2/c-erbB-2/neu DNA immunization on mouse tumor cells expressing exogenous human or rat p185neu but not on mouse tumor cells naturally expressing mouse p185neu has been demonstrated. We investigated the feasibility of using N-terminal rat neu DNA immunization on mouse tumor overexpressing endogenous p185neu and enhancing the therapeutic efficacy of this vaccine by fusion to various cytokine genes, including interleukin-2 (IL-2), interleukin-4 (IL-4), or granulocyte-macrophage colony-stimulating factor. In a therapeutic model, N'-neu-IL-2 DNA vaccine was significantly better than N'-neu DNA vaccine, and N'-neu DNA vaccine was significantly better than control DNA or N'-neu-IL-4 DNA vaccine. The therapeutic efficacy of DNA vaccines was correlated with tumor infiltration of CD8+ T cells. Depletion of CD8+ T cells completely abolished the therapeutic effects of N'-neu-IL-2 DNA vaccine and N'-neu DNA vaccine. Depletion of CD4+ T cells after tumor implantation had no influence on N'-neu-IL-2 DNA vaccine, but enhanced the therapeutic efficacy of N'-neu DNA vaccine. Our results demonstrate that rat N'-neu DNA vaccine has a therapeutic effect on established tumor through the CD8+ T-cell-dependent pathway. Depletion of CD4+ T cells or fusion to the IL-2 gene can thus further enhance the therapeutic effects of N'-neu DNA immunization on mouse tumor expressing endogenous p185neu.

Animals↗
PubMed2005

Noninvasive imaging of ex vivo intracoronarily delivered nonviral therapeutic transgene expression in heart.

We developed a clinically applicable approach for noninvasive monitoring of reporter-therapeutic linked gene expression in the whole heart of large animals using PET imaging and further validated the efficacy and cardiac adverse effects of reporter-therapeutic linked gene transfer in a rabbit cervical heterotopic functional heart transplant model. Cationic liposome complexed with a vector containing a herpes simplex virus type 1 mutant thymidine kinase (HSV1-sr39tk) as the reporter gene and a recombinant human immunosuppressive cytokine, interleukin-10 (hIL-10), as the therapeutic gene was ex vivo intracoronarily delivered into cardiac allografts before implantation. Long-term HSV1-sr39tk and hIL-10 transgene and protein overexpression associated with myocardial PET reporter probe 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) accumulation was observed in the allografts. The expression of the HSV1-sr39tk gene was significantly correlated with the hIL-10 gene expression and the total myocardial [18F]FHBG accumulation quantified as a percentage of intravenously injected [18F]FHBG dose. A homogeneous distribution of [18F]FHBG accumulation was seen in the whole heart similar to the distribution of [18F]fluorodeoxyglucose, a PET glucose metabolism probe. The immunosuppressive therapeutic efficacy remained the same in allografts treated with reporter-therapeutic linked gene and therapeutic gene only. No cardiac adverse effect was found. Our results demonstrate for the first time that PET reporter-therapeutic linked gene imaging is applicable for noninvasively monitoring ex vivo intracoronarily delivered therapeutic transgene expression in the whole heart.

Animals↗
PubMed1997

Wire-directed localization biopsy of the breast: an audit of results and analysis of factors influencing therapeutic value in the treatment of breast cancer.

Fine-wire localization biopsy is an accurate technique for diagnosis of mammographically-detected breast abnormalities, and may also be therapeutic in the management of impalpable malignant lesions. A number of factors were therefore examined regarding their influence upon therapeutic success in a consecutive series of 129 localization biopsies. Factors included type of radiological abnormality, method and accuracy of wire localization and pre-operative cytology. Primary malignancy was detected at initial localization in 64 cases (malignant:benign ratio, 1.11:1); 26 (41%) achieving adequate local tumour excision margins without further surgery, and 38 undergoing further surgery to clear margins (mastectomy in 23, further wide excision in 15). Therapeutic success was related to the accuracy of pre-operative needle localization (needle hook within 1 cm of target lesion in 26/26 (100%) therapeutic biopsies, compared to 29/38 (76%) non-therapeutic biopsies (P<0.01, Fisher's exact test)); and to pre-operative cytology (suspicious/malignant cytology in 15/24 therapeutic, compared with only 9/29 non-therapeutic biopsies (P=0.013, chi-squared)). Localization biopsy has a high diagnostic success rate and a therapeutic value dependent upon accurate pre-operative cytological diagnosis, supplemented by precise needle localization of the target lesion.

Adenocarcinoma↗