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PubMedDate not supplied

Determination of therapeutic doses of bisquaternary oximes in large animals.

This report presents a non-lethal method for estimating a range of therapeutic doses of bisquaternary oximes that serve as antidotes against organophosphorus poisoning. We have estimated therapeutic oxime doses that are equivalent in their relative toxicity rather than selecting arbitrary fractions of their LD(50). Thus, toxic signs of the oximes HI-6, HLö-7, Toxogonin, AB-8 and AB-13 were monitored quantitatively in baboon monkeys and beagle dogs. Using Toxogonin as a reference oxime, a calculated unit of equivalent dose (CED) was defined as the oxime dose equal to the ratio between its minimal toxic dose (MTD) and the therapeutic ratio (TR) of Toxogonin i.e. CED = MTD/TR. Assuming that the tails of dose-response curves of toxicity for bisquaternary oximes are shallow and similar to one another, one could substitute the ED(10) for the MTD. The ED(10) values for bisquaternary oximes were estimated using the log-log model following experimental observations and quantitative scoring of toxic signs in dogs and monkeys. The MTD values then were calculated using the ED(10) values and the experimental therapeutic dose of the reference oxime Toxogonin. The following CED values were obtained for AB-8, AB-13, Toxogonin, HI-6 and HLö-7 in dogs (d) and monkeys (m): 98.7, 74.2, 30.0, 14.5 and 12.1 (d) and 281.9, 232.1, 41.7, 192.9 and 92.9 (m) micromol kg(-1), respectively. The antidotal efficacy of these oximes against poisoning by the nerve agent tabun was determined in dogs and monkeys. These dose-dependent efficacy data were obtained at 0.3 x CED, 1 x CED and 3 x CED of oximes in combination with atropine. These data provide comparative therapeutic values using oxime doses based on their relative toxicity. The highest antidotal efficacy against tabun in dogs was obtained for toxogonin, whereas HLö-7 and AB-13 were most efficacious in monkeys.

Animals↗
PubMed2025

Microbiome therapeutic PMC101 inhibits the translocation of carbapenem-resistant Klebsiella while enhancing eubiosis in antibiotic-induced dysbiosis mice.

Carbapenem-resistant Enterobacteriaceae (CRE), known for their extensive antibiotic resistance, pose a severe global medical threat. Therefore, developing novel therapeutics beyond conventional antibiotics is urgently needed, and the importance of microbiome therapeutics is increasingly being recognized. This study explores the expanded systemic efficacy of PMC101, a microbiome therapeutic, beyond intestinal CRE infections and investigates its mechanism of action from a microbiome perspective. First, the genetic characteristics of the novel strain were identified through whole-genome analysis, and a scalable cultivation process was established as part of the overall development of this microbiome therapeutic. PMC101 increased the survival rate to 100%, significantly reduced disease severity scores, and prevented weight loss in CRE-infected mice treated with antibiotics. These effects are attributed to the inhibition of CRE growth in stool and the reduced detection of CRE in the lungs and kidneys, indicating suppression of systemic translocation. Metagenomic analysis revealed that PMC101 prevented the reduction in microbial population caused by antibiotics and CRE infection, restored species diversity indices, and mitigated dysbiosis while promoting eubiosis. This CRE translocation suppression was closely associated with increased CRE translocation-microbiome index, defined as the ratio of Bacteroidetes to Proteobacteria. This relationship was further confirmed through simulations using a human intestinal microbial ecosystem model. Additionally, increases in short-chain fatty acids, reductions in excessive inflammatory responses, and decreases in tissue damage were observed, all of which contribute to preventing CRE translocation. Finally, pathogen inhibition effects and safety tests were conducted, confirming the prophylactic potential of PMC101 as a microbiome therapeutic. These findings strongly support PMC101 as a promising candidate for future microbiome-based therapies against CRE infections.

Animals↗
PubMed2007

Multislice CT-angiography in percutaneous postinterventional hematuria and kidney bleeding: Influence of diagnostic outcome on therapeutic patient management. Preliminary results.

BACKGROUND: The aims of this study were to assess the value of multislice CT-angiography (MS-CT-A) in percutaneous postinterventional kidney bleeding and to determine the influence of diagnostic outcome on therapeutic patient management. A recommendation for the interdisciplinary patient work-up for the emergency room was offered. METHODS: Between April 2003 and January 2006, 12 patients with hematuria and clinically suspected renal bleeding underwent MS-CT-A for emergency diagnostic assessment. The spectrum of kidney injuries on CT was analyzed according to an organ-scaling scheme. The efficacy of MS-CT-A with regard to confirmation of active arterial bleeding was evaluated as well as the therapeutic consequences for patient management. RESULTS: In seven patients (59%) staged grade V renal injury, active renal arterial bleeding was detected on CT-A. Patients immediately underwent therapeutic angiography with confirmation of arterial bleeding and successful embolization. Four patients (33%) were staged grade I renal injury with subcapsular kidney hematoma but no active hemorrhage. Therefore, these patients were not exposed to further therapeutic intervention. One patient (8%) was diagnosed grade II renal injury with superficial cortical renal parenchyma tear and no active bleeding on CT-A. CONCLUSIONS: MS-CT-A is a valuable, fast and objective emergency tool for assessment of postinterventional renal hemorrhage. Detection of contrast material extravasation to affirm ongoing arterial bleeding and to localize bleeding site at the level of segmental or interlobar renal artery is a predictor for the need for further treatment and justifies therapeutic radiological or surgical management.

Adult↗
PubMed1999

A multiple-dose safety and bioequivalence study of a narrow therapeutic index drug: a case for carbamazepine.

BACKGROUND AND OBJECTIVES: Carbamazepine is among those drugs that have been considered to have a narrow therapeutic plasma concentration range, that is, a narrow therapeutic index. Although the US Food and Drug Administration has approved new generic products based on standard single-dose bioequivalence studies, several state formularies, including the New Jersey Drug Utilization Review Council, have recently established additional criteria for acceptance of bioequivalence of narrow therapeutic index drugs, limiting the use of some approved generic drugs in specific states. To further validate the adequacy of single-dose studies for the determination of bioequivalence of narrow therapeutic index drugs, a multiple-dose study was conducted that more closely reflected therapeutic use. METHODS: A single-center, multiple-dose, randomized, open-label, 2-way crossover bioequivalence study was conducted in 32 fasting volunteers at steady state. Subjects received the test and reference products as a 200 mg carbamazepine tablet 3 times a day in a crossover fashion. Concentrations of carbamazepine and carbamazepine-10,11-epoxide in plasma were measured by a validated specific HPLC method. RESULTS: A total of 28 subjects completed the study. Pharmacokinetic parameters and measures of fluctuation for both products at steady state were similar, with 90% and 95% confidence intervals falling within 90% and 110%. CONCLUSION: The multiple-dose study provided reliable safety and bioequivalence data under rigorous statistical conditions and confirmed bioequivalence of test and reference products determined by a single-dose study.

Adult↗
PubMed2000

[Program for the substitution of therapeutic equivalents in the hospital setting].

BACKGROUND: A Program of Therapeutic Equivalents (TEP) is here reported which was elaborated and is currently in force at a third level university teaching hospital. MATERIALS AND METHODS: Therapeutic equivalents were selected within the same pharmacologic group on the basis of approved indications and both efficiency and safety data. RESULTS: TEP considers: a) the substitution of drugs which are considered therapeutic equivalents; b) withdrawal of drugs which have not proved efficiency or are of no interest for inpatients; c) continuation of therapies when changes are not advisable, and d) indistinct use of homologous drugs. From August 1998 up to April 1999, TEP was applied in 505 occasions; it was accepted in 499 (99%) and rejected in 6 (1%). DISCUSSIONS: The substitution of therapeutic equivalents should be viewed in the context of selecting the most appropriate drugs to be used in the hospital setting. TEP should be a consensus document and supervised by the Pharmacy and Therapeutics Commission.

Hospitals, University↗
PubMed2002

Should therapeutic abortion be legal in Nicaragua: the response of Nicaraguan obstetrician-gynaecologists.

Abortion is legal in Nicaragua only to save the life of the woman. In 2002, amendments to the Penal Code to change the penalties for obtaining and providing illegal abortions and regulations on the authorization of legal abortions are due to be debated in the legislature. In a context of extensive media coverage and debate between women's health and rights groups and a powerful movement to make all abortions illegal, medical professionals have also been effective in influencing law and policy. In May 2001, the Nicaraguan Society of Obstetrics and Gynecology presented the results of a study of the views of 198 obstetrician-gynaecologists on pending legislation regulating therapeutic abortion and the medical and ethical implications of providing therapeutic abortion services. All but nine of the 198 participants in the study, who comprised 76% of all registered obstetrician-gynaecologists in Nicaragua, believed that therapeutic abortion should not be criminalized and over 90% believed that there were cases in which therapeutic abortion was necessary to save women's lives. Some also supported legislative reform to allow abortion in cases of rape and fetal malformation. These results countered claims by the Nicaraguan Medical Association (AMN), taken up by the Church and anti-abortion legislators and groups, that therapeutic abortion was no longer necessary due to modern medicine. The election of anti-abortion politicians to powerful positions in early 2002 has created a formidable challenge when the proposed revisions to the Penal Code are debated.

Abortion, Therapeutic↗
PubMed1997

Reducing anxiety: the employment of Therapeutic Touch as a nursing intervention.

Patient anxiety is frequently associated with admission and treatment in Critical Care Units. In Critical Care, one aim is the promotion of comfort so that anxiety experienced by patients can be reduced. In this article, a quasi-experimental design which attempted to determine the effectiveness of Therapeutic Touch as a nursing intervention is described. It was hypothesized that Therapeutic Touch would promote comfort and reduce anxiety. Before implementation of the project, a semi-structured interview was conducted amongst nurses (n = 18) from an Intensive Care Unit in a District General Hospital in East London. Interviews were conducted in order to determine the nurses' perceptions of the effectiveness of Therapeutic Touch as a complementary therapy. Initial findings of nurse interviews, a nurse's personal experiences of administering Therapeutic Touch and a case study indicate there may be a place for Therapeutic Touch as an intervention for promoting comfort and reducing anxiety in Critical Care.

Adult↗
PubMed1998

Reflection of a therapeutic touch experience: case study 2.

The purpose of this case study was to explore the experience of both giving and receiving Therapeutic Touch. A subjective account of the Therapeutic Touch experience is given in an attempt to throw light on its unique creative and therapeutic qualities. In most instances it was shown that the experience of both giving and receiving Therapeutic Touch was a parallel experience. This case study explores the effects of Therapeutic Touch on a client experiencing pain and associated anxiety. Whilst a response to treatment was observed, the need for further case studies and research studies in this area was identified.

Adult↗
PubMed1998

Developing a non-aversive intervention strategy in the management of aggression and violence for people with learning disabilities using natural therapeutic holding.

This paper builds upon a previous piece of research regarding the development of 'natural therapeutic holding' as a non-aversive alternative to control and restraint (C and R) in managing aggression and violence in people with learning disabilities. This paper represents aspects of an ongoing programme of research and explains the aims and values which underpin natural therapeutic holding by describing the theory, aims, values and practical application. The concepts of individual risk management and pro-active intervention strategies are discussed with illustrations of practical application given by means of a case study. The case study shows that over a relatively short period of time, an individual with severe learning disabilities who is aggressive and violent, learns alternative coping strategies to aggression and violence through the application of natural therapeutic holding. The article concludes that natural therapeutic holding is a very effective intervention strategy in the management of violence in people with learning disabilities from two perspectives: (a) it provides staff with safe, professional and ethical skills with which they can manage aggressive and violent clients and (b) as a therapy, natural therapeutic holding gives clients the opportunity to learn coping strategies which are more effective than violence.

Adaptation, Psychological↗
PubMed1998

The use of leisure activities in a therapeutic community.

This paper is concerned with the use of social and leisure activities as part of nursing work in a therapeutic community. It describes this element in the therapeutic programme of the Cassel Hospital. There is a brief introduction to the general principles of the therapeutic community and then to the nurses' role at the Cassel Hospital. The work in the sphere of social and leisure activities is seen as consistent with these principles. The structures enabling social and leisure activities to be integrated into the work of the hospital are described. Therapeutic opportunities are outlined, which arise when nurses work alongside patients in the course of such activities. This also serves to illustrate therapeutic community practice. There follows a discussion of the clinical significance of the voluntary element in this area of practice and of the related problems. Jacques' conceptualization of work and resistance to work are used at a number of points to link issues raised in the paper to existing psychodynamic theory.

Hospitals, Psychiatric↗
PubMed2004

TRMP: a database of therapeutically relevant multiple pathways.

UNLABELLED: Disease processes often involve crosstalks between proteins in different pathways. Different proteins have been used as separate therapeutic targets for the same disease. Synergetic targeting of multiple targets has been explored in combination therapy of a number of diseases. Potential harmful interactions of multiple targeting have also been closely studied. To facilitate mechanistic study of drug actions and a more comprehensive understanding the relationship between different targets of the same disease, it is useful to develop a database of known therapeutically relevant multiple pathways (TRMPs). Information about non-target proteins and natural small molecules involved in these pathways also provides useful hint for searching new therapeutic targets and facilitate the understanding of how therapeutic targets interact with other molecules in performing specific tasks. The TRMPs database is designed to provide information about such multiple pathways along with related therapeutic targets, corresponding drugs/ligands, targeted disease conditions, constituent individual pathways, structural and functional information about each protein in the pathways. Cross links to other databases are also introduced to facilitate the access of information about individual pathways and proteins. AVAILABILITY: This database can be accessed at http://bidd.nus.edu.sg/group/trmp/trmp.asp and it currently contains 11 entries of multiple pathways, 97 entries of individual pathways, 120 targets covering 72 disease conditions together with 120 sets of drugs directed at each of these targets. Each entry can be retrieved through multiple methods including multiple pathway name, individual pathway name and disease name. SUPPLEMENTARY INFORMATION: http://bidd.nus.edu.sg/group/trmp/sm.pdf

Biomarkers↗
PubMed1999

Evolving experience with direct puncture therapeutic embolization for adjunctive and palliative management of head and neck hypervascular neoplasms.

OBJECTIVES: The use of percutaneous, direct puncture therapeutic embolization (DPTE) of hypervascular head and neck neoplasms is a relatively new modality that may be used to supplement or supplant conventional endovascular transarterial embolization. Although the preliminary clinical experience reported by a single group has been favorable, extensive case series experience is lacking. This prompted us to review our recent clinical experience with these techniques to determine safety, efficacy, and emerging role in the overall neurointerventional therapeutic armamentarium. STUDY DESIGN: A retrospective analysis of the previous 34 consecutive cases of hypervascular tumors undergoing DPTE referred to our service for therapeutic devascularization was performed. METHODS: Complete case record review was undertaken. Twenty-six of 34 cases involved DPTE of head and neck neoplasms. Conventional diagnostic angiography was performed for therapeutic planning and to assist in precise localization. When performed, standard microcatheter transarterial embolization techniques were used either before or after attempted DPTE. Cyanoacrylate embolic mixtures (n-butyl cyanoacrylate [NBCA], lipiodol, powdered tungsten) were used in 21 of 24 cases, and absolute ethanol in 3 of 24. Direct puncture angiography of the targeted tumor neovasculature was always performed before DPTE. RESULTS: Twenty-four of 26 cases had technically successful DPTE. Combined transarterial embolization with DPTE was used in 16 of 24 cases, although for the last 12 cases, 9 were treated predominantly or exclusively by DPTE. There were no major or minor clinical complications, and there was one asymptomatic technical complication. Total or near-total devascularization was achieved in all cases. All preoperative cases had excellent hemostasis within the resected tumor bed. CONCLUSIONS: Our results lend further support to the safety and efficacy of DPTE in the management of hypervascular neoplasms of the head and neck. With our increasing experience, this technique is evolving into a primary therapeutic modality for optimal tumor devascularization.

Adult↗
PubMed1988

What are the prerequisites and indications of the therapeutic community proper? A comparative study.

Is the therapeutic community model appropriate for short term psychiatric wards with catchment area responsibility and emergency obligations? A comparative study of group dynamics, measured by Group Emotionality Rating System and Group Focal Conflict Analysis within three different therapeutic community wards, revealed that the short term ward contained extreme fight/flight groups and pseudo-groups unable to deal with the delegated responsibility presupposed by the therapeutic community model. The intermediate ward functioned fairly well, while the long term ward for psychotherapy of schizophrenia and personality disorders also functioned badly from a therapeutic community proper point of view. The author discusses these findings in light of previous literature and concludes that the therapeutic community proper is predominantly a treatment model relevant for personality disorders and severe neuroses, and not adequate for the multiplicity of emergency tasks facing a short term psychiatric ward.

Group Processes↗
PubMed1994

Percutaneous transcatheter retrieval of misplaced therapeutic embolisation devices.

OBJECTIVE: To assess the incidence and subsequent management of misplaced devices as a complication of therapeutic embolisation procedures. DESIGN: Retrospective review of case notes, cardiac catheterisation reports, and angiograms. SETTING: Tertiary referral centre for congenital heart disease. PATIENTS: 205 consecutive children and adults undergoing therapeutic embolisation for congenital heart disease in the 10 years up to 1 April 1993. This group had 231 therapeutic embolisation procedures at 241 sites using coils, umbrella devices, or detachable balloons. MAIN OUTCOME MEASURES: Incidences of misplacement and retrieval of the device; morbidity and mortality. RESULTS: The incidence of misplacement was 3% (10/332) of devices deployed and 4.3% (10/231) of procedures performed. Retrieval from distal pulmonary arteries was not attempted in two patients, but transcatheter retrieval of coils and umbrellas from systemic and pulmonary vessels, using snares or retrieval baskets, was successful in the remaining eight. There were no deaths or serious sequelae related to the procedure, but one patient required femoral arteriotomy for removal of an umbrella device retrieved only as far as the groin. In four of the five most recent cases, the misplaced device was retrieved and the therapeutic embolisation was completed at the same procedure. CONCLUSIONS: Misplacement of a device during therapeutic embolisation is a recognised complication that can be satisfactorily dealt with by transcatheter retrieval without recourse to surgery. For retrieval to be successful it is important to have a wide selection of retrieval equipment available and to be conversant with its use.

Adolescent↗
PubMed2004

The development of the therapeutic community in correctional establishments: a comparative retrospective account of the 'democratic' Maxwell Jones TC and the hierarchical concept-based TC in prison.

BACKGROUND: The correction-based therapeutic community (TC) is one of the most described treatment modalities for (substance abusing) incarcerated offenders. The origins and development of the therapeutic community have been traced back to two independent traditions: the American hierarchical concept-based TC and the British democratic Maxwell Jones-type TC. Both branches have developed independently, targeting different people and tackling diverse problems. AIMS: To demonstrate that there are clear and undeniable similarities between the 'two' prison-based therapeutic communities. METHOD: A comparative historical review of the literature and a critical discussion and comparison. RESULTS: The links between the democratic and hierarchical therapeutic communities are summarised under five headings: social learning and behavioural modification; permissiveness and modelling; democracy and hierarchy; communalism and community as method; reality testing and 'acting as if'. CONCLUSIONS: The 'two' correction-based therapeutic communities are on converging pathways. Far from being oppositional models, they can be regarded as being complementary.

Behavior Therapy↗
PubMed1998

The efficacy of therapeutic touch for improving functional ability in elders with degenerative arthritis.

The purpose of this Rogerian study was to determine whether therapeutic touch improved functional ability in elders with arthritis as compared to routine treatment and progressive muscle relaxation. Eighty-two non-institutionalized elders were randomly assigned to therapeutic touch or progressive muscle relaxation treatments. Subjects served as their own control for 4 weeks, then received six treatments at 1-week intervals. Pain, tension, mood, and satisfaction improved after therapeutic touch and progressive muscle relaxation. Hand function improved after therapeutic touch; walking and bending improved after progressive muscle relaxation. Functional ability was significantly different between the two groups for mobility and hand function. Lower scores (indicating better function) were attained by the therapeutic touch group.

Activities of Daily Living↗
PubMed1992

Clinical aspects of therapeutic substitution.

A variety of problems are associated with the operation, quality, costs, and benefits of therapeutic substitution programmes. Adequate communication of procedures, events, and failures are essential features of a safe therapeutic substitution policy. However, case reports of suboptimal therapy and differences in pharmacological profiles of related agents indicate the potential for clinical nonequivalence even between similar drugs of a class. Suboptimal or failed therapy associated with such nonequivalence may offset savings in drug costs resulting from therapeutic substitution. Thus, consultation on behalf of each patient is necessary for optimal therapy and maximum cost savings. Currently, there are no data on the interchangeability of specific agents of a class and the effects of therapeutic substitution on overall treatment costs. Thus, the health and economic outcomes of therapeutic substitution policies are unknown.

Clinical Protocols↗
PubMed1996

Liposome longevity and stability in circulation: effects on the in vivo delivery to tumors and therapeutic efficacy of encapsulated anthracyclines.

The effect of liposome composition on drug delivery to tumors and therapeutic efficacy of liposome-encapsulated anthracyclines was investigated in two murine tumor models: an ascitic tumor (J6456 lymphoma) and a solid carcinoma (M-109). Longevity in circulation correlated positively with high drug levels in the extracellular (ascitic) tumor fluid and with delayed peak tumor levels. Using polyethylene-glycol(PEG)-coated liposomes, liposome stability (drug retention) was found to be an important determinant of therapeutic efficacy, as indicated by the superior survival conferred by high Tm phosphatidylcholines (hydrogenated, dipalmitoyl) over low Tm (egg phosphatidyl-choline). Replacing PEG with another negatively-charged surface headgroup (phosphatidyl-glycerol, phosphatidyl-inositol) resulted in relatively shorter longevity in circulation of the liposome-associated drug, but no detectable differences in anti-tumor efficacy. When neither the surface charged headgroup nor the PEG coating are present, the resulting drug formulation was significantly less effective than PEG and phosphatidylinositol-based formulations in both tumor models. In conclusion, longevity in circulation, as obtained with PEG coating, tends to improve the therapeutic efficacy of liposome-encapsulated anthracyclines. The current therapeutic models were however unable to detect differences between the therapeutic activity of PEG and other liposome formulations with relatively small differences in circulation longevity.

Animals↗