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At least 73 records · Page 4Linked to original sources
PubMed2005

Individualised cancer therapeutics: dream or reality? Therapeutics construction.

The analysis of DNA microarray and proteomic data, and the subsequent integration into functional expression sets, provides a circuit map of the hierarchical cellular networks responsible for sustaining the viability and environmental competitiveness of cancer cells, that is, their robust systematics. These technologies can be used to 'snapshot' the unique patterns of molecular derangements and modified interactions in cancer, and allow for strategic selection of therapeutics that best match the individual profile of the tumour. This review highlights technology that can be used to selectively disrupt critical molecular targets and describes possible vehicles to deliver the synthesised molecular therapeutics to the relevant cellular compartments of the malignant cells. RNA interference (RNAi) involves a group of evolutionarily conserved gene silencing mechanisms in which small sequences of double-stranded RNA or intrinsic antisense RNA trigger mRNA cleavage or translational repression, respectively. Although RNAi molecules can be synthesised to 'silence' virtually any gene, even if upregulated, a mechanism for selective delivery of RNAi effectors to sites of malignant disease remains challenging. The authors will discuss gene-modified conditionally replicating viruses as candidate vehicles for the delivery of RNAi.

Animals↗
PubMed1994

Trazodone. A review of its pharmacology, therapeutic use in depression and therapeutic potential in other disorders.

Trazodone is a triazolopyridine derivative, chemically and pharmacologically unrelated to other currently available antidepressants. It possesses antidepressant, and also some anxiolytic and hypnotic activity. Results from a small number of short term (4 to 6 weeks) comparative studies in a total of 320 evaluable elderly patients with major depression, suggest that trazodone at therapeutic doses is superior to placebo and as effective as amitriptyline, imipramine, fluoxetine and mianserin in relieving depressive symptoms. Trazodone has also been successfully used in a small number of patients with depression and pre-existing cardiovascular disease. More recently, trazodone has been used as a hypnotic for psychotropic-induced or other insomnias with some success. However, further clinical experience is needed to confirm these preliminary results. In the elderly, maximum tolerated doses of trazodone are 300 to 400 mg/day, although higher doses of up to 600 mg/day are tolerated by younger patients. Drowsiness is commonly reported, but the incidences of both anticholinergic and cardiovascular effects were notably lower in elderly patients treated with trazodone compared with older tricyclic antidepressants. However, undesirable effects such as orthostatic hypotension, arrhythmias and priapism need to be closely monitored. In comparison with other currently available agents, particularly the tricyclic antidepressants, trazodone is relatively safe in overdose. In terms of therapeutic efficacy, trazodone appears to confer little advantage over other available antidepressants. While limited data suggest that trazodone may be better tolerated than older tricyclic antidepressants, especially in the elderly, there is a paucity of data at present comparing trazodone with the secondary amine tricyclic agents, serotonin reuptake inhibitors or moclobemide. Bearing this in mind, trazodone may be of use in elderly patients in whom anxiety and insomnia are problematic, and in those patients who are unresponsive to or cannot tolerate therapy with other agents. Studies are also required to define the place of trazodone in long term prophylactic therapy for recurrent depression. Future trials comparing both its efficacy and tolerability with those of newer agents will ascertain whether trazodone becomes a first line agent within these subsets of elderly patients.

Aged↗
PubMed2004

G protein-coupled receptors and their signaling pathways: classical therapeutical targets susceptible to novel therapeutic concepts.

In recent years, new strategies in cancer therapy have been developed targeting key signaling molecules in the receptor tyrosine kinase signal transduction pathway. In contrast, most therapeutical concepts to manipulate G protein-coupled receptors (GPCR)-mediated disorders are still limited to the use of receptor-specific agonists or antagonists. Visible progress in the understanding of GPCR signaling complexity, especially the detection of several families of highly target- and cell-specific regulator proteins of GPCRs, G proteins, and effector components may open new horizons to develop novel therapeutical concepts targeting GPCR signaling elements. Thus, this review will focus on different molecular levels that may be of particular interest in terms of new drug development such as: (i) GPCR subtypes, allosteric binding sites, dimerization and constitutive activity, the use of RAMPs (receptor-activity-modifying proteins) and RASSLs (receptor activated solely by synthetic ligands); (ii) AGS (activators of G protein signaling) and RGS (regulators of G protein signaling) proteins which modify G protein activity; (iii) the high diversity of isozymes involved in the generation, signal transmission, and degradation of second messenger molecules.

Animals↗
PubMed1999

Therapeutic substitution and therapeutic conservatism as cost-containment strategies in primary care: a study of fundholders and non-fundholders.

BACKGROUND: General practice (GP) fundholders contained prescribing costs by restricting the rise in volume of prescribing and by increasing generic prescribing. It is uncertain whether they used more sophisticated approaches to medicine choice in attempts to contain costs. AIM: To examine whether fundholding practices have adopted medicine-specific strategies to contain prescribing costs--i.e. switching to less expensive but equally effective medicines or resisting the uptake of newer more expensive medicines--by examination of the prescribing of ulcer-healing and antidepressant medicines in the period before and after practices became fundholders. METHOD: Comparison of prescribing data of 52 fundholding practices before fundholding and after fundholding with that of matched non-fundholding practices. Measures examined were prescribing costs (net ingredient cost in each therapeutic area per ASTRO-pu); prescribing volume (defined daily doses per ASTRO-pu); the proportion of all ulcer-healing medicines prescribed as cimetidine, ranitidine, nizatidine, and as proton pump inhibitors; and the proportion of all antidepressant medicines prescribed as selective serotonin re-uptake inhibitors. RESULTS: In comparison with non-fundholding practices, fundholders increasingly prescribed less expensive medicines (cimetidine and nizatidine) within the class of histamine2 receptor antagonists. However, fundholders adopted proton pump inhibitors or selective serotonin re-uptake inhibitors at the same rate as non-fundholders. CONCLUSION: Fundholders have used therapeutic substitution with medicines of equal effectiveness to contain prescribing costs. There is no evidence that fundholders have been slower than non-fundholders to use newer, more expensive medicines.

Aged↗
PubMed2003

Observance in diabetes: from therapeutic education to therapeutic alliance.

The aim of this paper is to understand why non-observance is so frequent in diabetic patients, to delineate some of its mechanisms, which should make it possible to propose approaches to prevent non-observance. This will lead us to clarify the relationship between therapeutic education and observance, and to justify on a theoretical basis the concept of therapeutic alliance.

Diabetes Mellitus↗
PubMedDate not supplied

[The current physiopathological, diagnostic, clinical and therapeutic considerations of peptic ulcer. A comparison between traditional and modern therapeutic methods].

The authors, keeping in mind their clinical, diagnostic and therapeutic experience on ulcerous gastric and duodenal pathology, underline the effectiveness of the traditional antacids as well as that of the modern up-to-date antisecretory and cytoprotective agents. After having put into evidence the causes that can provoke peptic ulcer not excluding that of iatrogenic and their probable aetiopathogenetic mechanism and having hinted at another pathology that uses the same therapeutic remedies, the gastro-oesophagus reflux, they discuss in detail the active principles used in the gastric or duodenal pathology, the possible side and/or secondary effects that in the long run are determined when using only the modern therapy with the usual antacids. Therefore, they hope that these therapies are used after carefully considering the general clinical and anatomicopathologic situation of the lesion that must be created.

Antacids↗
PubMed1988

[Lung diseases during therapeutic aplasia: diagnostic and therapeutic strategy].

Lung diseases that occur in patients with drug-induced bone marrow aplasia are part of a wider group of lung diseases in immunocompromised patients. Their most common causes are infections due to Gram-negative bacilli, staphylococci or Aspergillus spp. and intra-alveolar haemorrhages. Their diagnostic approach is often limited by disorders of coagulation, risks of infection by bronchial or pulmonary seeding during endoscopy and the lethal risk of mechanical ventilation after bronchoalveolar lavage in patients with respiratory failure. The therapeutic approach is frequently empirical due to the fact that antibiotic therapy cannot be delayed, even for a few hours, and to the aforementioned diagnostic problems. In practice, the diagnostic and therapeutic approaches usually result from a rational compromise depending on whether the lung disease has occurred at the onset or at the end of an episode of bone marrow aplasia.

Humans↗
PubMed1995

International study of expert judgment on therapeutic use of benzodiazepines and other psychotherapeutic medications: III. Clinical features affecting experts' therapeutic recommendations in anxiety disorders.

Our objective was to assemble expert clinical experience and judgment in the treatment of anxiety and related disorders in a systematic, quantitative manner. This article reports on some clinical features apart from diagnosis that may affect choice of strategy in the pharmacotherapy of anxiety disorders. A panel of internationally recognized experts in treating anxiety and depression was constituted by multistage peer nomination. Ninety percent (66 of 73) completed an extensive questionnaire. This report focuses on the expert panel's responses to questions on therapeutic options, based on multi-part case vignettes of several anxiety disorders presenting clinical variations within the same diagnosis. In the presence of higher levels of functional impairment, the experts more often recommended formal psychosocial procedures for adjustment disorder; medication for agoraphobia, social phobia, obsessive-compulsive disorder, and adjustment disorder; and polypharmacy for agoraphobia. Their therapeutic recommendations were not materially affected by chronicity in the case of panic disorder. Under the condition of heavy use of alcohol in the case of generalized anxiety disorder, the experts avoided benzodiazepines in favor of various other medications. In the presence of a serious cardiac conduction defect in the case of obsessive-compulsive disorder, they less often recommended medication. Those who did recommend medication changed their preference from tricyclic antidepressants (clomipramine) to selective serotonin reuptake inhibitors. Under the condition of a more severe precipitating event in the case of adjustment disorder, the experts were more likely to recommend both formal psychosocial intervention and medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

The therapeutic efficacy of murine anti-tumor T cells: freshly isolated T cells are more therapeutic than T cells expanded in vitro.

Adoptive immunotherapy (AIT) involving transfer of tumor-sensitized T lymphocytes in combination with cyclophosphamide (CY)-injection results in the eradication of the C57BL/6J (B6) rhabdomyosarcoma, 76-9 and is associated with the accumulation of a large number of tumor-infiltrating lymphocytes (TIL). Using immune spleen cells (ISC) from B6 and congenic B6. PL. Thy-1a mice, it was shown that most (> or = 97%) of the TIL were donor-derived. This in situ increase in donor-derived T cells was confirmed by using positively-selected Thy- 1.1+ and Thy- 1.2+ TIL for AIT after isolating them from regressing tumors and expanding them in rIL-2. The extent of CD8+ TIL expansion in vivo correlated with the numbers of TIL adoptively transferred and this in turn determined the degree of anti-tumor effects. It was evident, however, that these in vitro-expanded TIL expressing mRNA for TNF alpha and IFN gamma were qualitatively different and therapeutically less efficacious than the T cells associated with ISC or with freshly-isolated TIL. Unlike freshly isolated TIL that expressed specific cytotoxicity towards the 76-9 targets in vitro, IL-2 expanded TIL killed 76-9 cells and unrelated tumor targets to the same extent. A cytotoxic CD8+ T cell line derived from ISC and selected for activity against the 76-9 tumor cells showed no therapeutic efficacy. The data suggest that, in this tumor model, expansion of CD8+ T cells in vitro selects against anti-tumor efficacy.

Animals↗
PubMed1983

Anti-therapeutic dimensions of a community meeting in a therapeutic milieu.

A central feature of many inpatient settings, especially those that attempt to be "therapeutic communities," is the community meeting. Such meetings are often quite large and difficult to manage, and therefore susceptible to confusion and chaos. The present article documents the difficulties associated with a community meeting in a particular hospital setting, which is often psychonoxious for patients and debilitating of staff morale. The need to define achievable tasks that are commonly understood and agreed upon is addressed. The confusion and paralysis that results when roles are not clearly delineated is described, as is the destructive potential of not carefully managing the various boundaries that define the relationship between the community meeting and the context in which it is conducted. Finally, the danger of insufficient structure in a community meeting is illustrated. Suggestions for conducting successful meetings are offered.

Group Processes↗
PubMed2000

Measuring client clinical progress in therapeutic community treatment. The therapeutic community Client Assessment Inventory, Client Assessment Summary, and Staff Assessment Summary.

The therapeutic community (TC) Client Assessment Inventory (CAI), Client Assessment Summary (CAS), and Staff Assessment Summary (SAS) are instruments developed from a comprehensive theory of TC treatment and recovery. They measure client self-report and staff evaluation of client progress along 14 domains of behavior, attitude, and cognitive change. The present article reports on the development of the instruments and findings from an analysis of data on 346 clients in TC treatment; including scale properties and cross-sectional client differences by treatment tenure. The instruments were administered over a 1-year period at two residential TC facilities. Findings indicate that both client and staff instruments reliably differentiate client clinical changes during treatment and client self-ratings are initially consistently higher than staff ratings. Clarifying and measuring changes in the individual during treatment is the first step in the effort to understand the change process and what steps can be taken to improve treatment effectiveness.

Adult↗
PubMed2006

Are therapeutic communities therapeutic for women?

This paper addresses the growing phenomena of therapeutic community (TC) treatment approaches for women in correctional settings. Although rapidly increasing in number across the country, there is very little empirical research to support the effectiveness of TC treatment for women. Therefore, the literature on the efficacy and effectiveness of TC treatment for women is reviewed in relation to the literature on women's treatment issues. The literature review highlights the gaps where TC treatment ignores or exacerbates issues that are common to addicted women, or uses methods that may be contradictory to women's recovery.

Domestic Violence↗
PubMed1985

[Monitoring of therapeutic neuroradiologic examination and therapeutic procedures using evoked potentials].

Interventional neuroradiology makes use of different diagnostic and therapeutic catheterization techniques. Treatments performed are local intraarterial thrombolytic therapy, embolization and occlusion of brain supplying arteries, percutaneous transluminal angioplasty and intraarterial application of drugs. These treatments make it most important to check the patients neurological state during the procedure. Intraoperative monitoring of evoked potentials offers the opportunity to get objective information about changes in certain central nervous system functions even in anaesthesized patients. Usually intraoperative monitoring is performed to obtain information whether the function of structures at risk remains stable or is altered by the operation. This represents a more passive, observing way of monitoring. During interventional neuroradiology one is enabled to take additionally a more active and experimental way of monitoring by using the advantages of special catheter techniques like series of reversible balloon occlusion or intraarterial drug application. This leads to a dialogue between the radiologist and the neurophysiologist about the safety or the risk of the next step during a procedure. There are mainly two types of new information that can be achieved by active monitoring: the identification of functional territories of single or multiple feeding vessels and new insights into hemodynamics and the establishing of new sufficient collaterals. We have used intraoperative neuromonitoring in 35 patients during interventional neuroradiology. Our findings will be summarized and the usefulness of the different monitoring methods will be discussed.

Amobarbital↗
PubMed1976

Therapeutic trial of aniline mustard in patients with advanced cancer. Comparison of therapeutic response with cytochemical assessment of tumor cell beta-glucuronidase activity.

Seventy-eight patients with advanced cancer received an adequate therapeutic trial with aniline mustard (NSC 18429). Significant anticancer activity with clinical benefit was demonstrated in five patients with cancer of the prostate and one patient with renal cancer. beta-glucuronidase levels in aspirate and imprint preparations of tumor cells were assessed by a timed cytochemical technique. A partial correlation appeared to exist between very intense glucuronidase staining and tumor regression in prostate and kidney lesions; however, these high levels were observed only rarely. Sequential observations in two patients demonstrated loss of enzymatic activity concomitant with development of clinical relapse.

Aniline Mustard↗
PubMed2001

[Therapeutic effectiveness. Effects, effectiveness and value of therapeutic interventions].

Terms such as efficacy and efficiency of treatment are presently taking on growing importance for medical practice. Two examples are the increasing limitation of cost reimbursement to evidence-based, scientifically proven therapeutic measures and assessment of efficiency in terms of budgeting. We briefly discuss the definition and application of important terms and concepts in this context and ethical and methodological problems involved.

Clinical Trials as Topic↗
PubMed1991

Therapeutic monitoring for cyclosporine: difficulties in establishing a therapeutic window.

Despite the fact that cyclosporine (CsA) has been used clinically for a number of years, there is still uncertainty about the efficacy of monitoring its blood levels. Few if any studies have documented clear differentiation of rejection, immunosuppression, and toxicity on the basis of CsA concentrations alone. The issues in CsA monitoring include selection of sample matrix, analytical method, dosing interval and the timing of trough measurements, the temporal relationship between measurements and physiological events such as toxicity, the concurrent presence of multiple other immunosuppressive agents, and the lack of "gold standards" for determining rejection, adequate immunosuppression, and toxicity. In contrast to using CsA levels for the differential diagnosis of rejection and toxicity, there is evidence that maintenance of CsA concentrations within a therapeutic window results in a lower prevalence of toxicity and rejection.

Cyclosporins↗
PubMed1993

Clinical, historic, and therapeutic features of cicatricial pemphigoid. A literature review and open therapeutic trial with corticosteroids.

Cicatricial pemphigoid is at present an incurable, autoimmune disease that involves mucosa and skin. We have documented the clinical, microscopic, and therapeutic features of 23 patients with cicatricial pemphigoid and added these to reports of past literature. The mean age at the time of diagnosis was 63 years, and women were involved twice as often as men. Eighty-three percent of patients had oral mucosal involvement, 70% had conjunctival involvement, and 22% had skin involved. Direct immunologic evaluation revealed IgG at the basement membrane in 57% of cases and C3 in 66%. We have been able to manage the disease adequately in most patients with topical or systemic corticosteroids. The most commonly encountered side effect was oral candidiasis.

Aged↗
PubMed1981

Preliminary studies on the validity of in vitro measurement of drug toxicity using HeLa cells. IV. Therapeutic effects and side effects of 50 drugs related to the HeLa toxicity of the therapeutic concentrations.

As a measure of the relevance to human drug effects of drug cytotoxicity in vitro, calculated and actual therapeutic blood concentrations of 50 drugs were divided by their 50% inhibitory concentrations for HeLa cells in vitro to make up three types of cytotoxic quotients (CQTv, CQTd, and CQTr). When the various quotients were compared with known cytotoxic effects of the drugs the parameters correlated well. While most drugs at single dosage reached concentrations with low quotients (CQTv and CQTd) corresponding to few reported cytotoxic effects and side effects, a substantial number of drugs at repeated dosage reached concentrations with high quotients (CQTr) corresponding to known or suspected cytotoxic action in man.

Cell Survival↗