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At least 55 records · Page 3Linked to original sources
PubMed1993

Loss of efficacy during long-term cifenline therapy: development of antiarrhythmic resistance?

OBJECTIVE: To describe the possible development of antiarrhythmic resistance to cifenline, an investigational Class I agent. METHODS: Forty patients with chronic ventricular premature depolarizations (VPDs) underwent dose-ranging studies with cifenline, an investigational Class I antiarrhythmic agent. Patients had a minimum of 30 VPDs/h detected by ambulatory electrocardiographic (ECG) monitoring over a 48-hour baseline placebo lead-in period. Twenty-two patients (55 percent) who initially responded received long-term cifenline therapy. Ambulatory ECG monitoring over 24 hours was repeated during active cifenline therapy at three-month intervals and during placebo reintroduction at six-month intervals. RESULTS: After an average follow-up of 28 months, VPD frequency during cifenline therapy was similar to that during initial baseline placebo therapy in 8 of the 22 patients (36 percent) who initially responded. Placebo reintroduction following cifenline failure showed a VPD frequency similar to that with active therapy. All patients had further cifenline dosage increases without success. Plasma cifenline concentrations increased in all patients and were in the high therapeutic range. All 8 patients were switched to other Class I antiarrhythmic agents with successful VPD suppression during treatment with the first alternative drug. CONCLUSIONS: We conclude that antiarrhythmic resistance occurred with cifenline in these patients as (1) initial efficacy was established for a minimum of two years, (2) VPD frequency was similar during cifenline therapy and placebo reintroduction, (3) cifenline therapy failure continued despite further dosage titration, and (4) alternative Class I antiarrhythmic therapy was successful in all patients. Repeat intermittent ambulatory ECG monitoring is necessary not only to assess the continued need for antiarrhythmic drug therapy, but also to establish continued long-term efficacy.

Adult↗
PubMed1995

A new psoralen-containing gel for topical PUVA therapy: development, and treatment results in patients with palmoplantar and plaque-type psoriasis, and hyperkeratotic eczema.

Topical photochemotherapy with psoralen and its derivatives 4,5',8-trimethylpsoralen (TMP) and 8-methoxypsoralen (8-MOP), with UVA irradiation, was evaluated with regard to minimum phototoxic dose, concentration, timing of UVA irradiation and systemic and local side-effects, in healthy volunteers. Psoralen (0.005%) in aqueous gel was found to be superior to TMP and 8-MOP in aqueous gel. No hyperpigmentation was seen after topical PUVA treatment with psoralen in aqueous gel. Patients with plaque-type psoriasis (n = 7), palmoplantar psoriasis (n = 7) and hyperkeratotic eczema (n = 2) were treated. Topical PUVA therapy was effective in most psoriasis patients, without the occurrence of local or systemic side-effects. Moreover, hyperkeratotic eczema patients who did not respond to conventional therapy showed partial remission. These results indicate that topical PUVA therapy with psoralen in aqueous gel is a useful therapeutic modality for treatment of psoriasis patients, and patients with recalcitrant dermatoses such as palmoplantar psoriasis and hyperkeratotic eczema.

Eczema↗
PubMed2002

Developing therapies for advanced bladder cancer.

Chemotherapy is an indispensable measure in the treatment of invasive or metastatic bladder cancer as even if metastases are not clinically apparent, the majority of cases of invasive bladder cancer are accompanied by micrometastases. At present, MVAC (methotrexate, vinblastine, adriamycin, cisplatin) is the gold standard for bladder cancer chemotherapy. There have consequently been many attempts at MVAC dose-intensification as well as many studies of the feasibility of neoadjuvant chemotherapy using MVAC. Unfortunately, the majority of results from these studies have been negative or contradictory. However, a recent large-scale randomised, controlled study yielded more promising results. Evidence has recently emerged which indicates that a useful chemotherapeutic strategy could possibly be devised by adjusting the dose and timing of MVAC. Increasing effort is also being put into the development of new gold standards for bladder cancer chemotherapy based on the use of newly developed antitumour drugs, and a number of candidates have emerged. It is hoped that the future we will see successful establishment of a number of useful regimens as a result of Phase III clinical studies using MVAC as their control regimen. For example, both gemcitabine and the taxanes, in combination with other drugs, are strong candidates for this purpose. The ultimate therapeutic strategy for bladder cancer will be a therapeutic approach which permits conservation of the bladder even when the malignancy is invasive and steady progress is already being made toward this goal, in limited cases, by means of multidisciplinary treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

[Effectiveness of isolation ultracentrifugation in the combined treatment of heart failure refractory to therapy developing in the presence of severe arterial hypertension with stable and malignant courses].

The feasibility and practicability of isolated ultrafiltration, or extracorporeal evacuation of excessive body fluid, was assessed in patients with severe stable and malignant arterial hypertension, complicated by refractory heart failure. This procedure, added to combined treatment, is a means to overcome resistance to medication, achieve a stable compensation of circulatory insufficiency symptoms, bring down arterial blood pressure and use smaller doses of hypotensive and diuretic drugs. Isolated ultrafiltration proves less effective in patients with cachectic circulatory insufficiency.

Acute Disease↗
PubMed1989

Observing client-therapist interaction in behaviour therapy: development and first application of an observational system.

A category system for coding the interaction in psychotherapy (CIP) is presented. Six therapists carried out 64 standardized intake sessions with clients presenting with chronic insomnia. The sessions were fully coded by three raters using the CIP. The 19 client categories as well as the 18 therapist categories showed sufficient reliability with kappa coefficients of 0.80 and 0.79 respectively. The frequencies of the client and the therapist categories of the first versus the second half of the interview were compared. Shifts in the behavioural patterns of therapists and clients during the course of the interviews are in accordance with the given rationale of the session. Correlations between the observational data and subjective ratings of the participants are further evidence for the utility of the CIP.

Adult↗
PubMed2025

Screening rare genetic diagnoses for amenability to bespoke antisense oligonucleotide therapy development: A retrospective cohort study.

PURPOSE: To estimate the proportion of molecular genetic diagnoses in a real-world, phenotypically heterogeneous patient cohort that are amenable to antisense oligonucleotide (ASO) treatment. METHODS: We retrospectively applied the N=1 Collaborative's Variant Assessments toward Eligibility for Antisense Oligonucleotide Treatment guidelines to all diagnostic variants found by clinical genome-wide sequencing at a single pediatric hospital in 532 patients over a 6-year period. Variants were classified as either "eligible," "likely eligible," "unlikely eligible," or "not eligible" in relation to the different ASO approaches, or "unable to assess." RESULTS: In total, 25 unique variants across 26 patients (4.9% of 532 patients) were eligible or likely eligible for ASO treatment at a molecular genetic level, via canonical exon skipping (4), splice correction (3), or messenger RNA knockdown (19). Only 8 of these molecular genetic diagnoses were made within a year of symptom onset. After considering disease and delivery related factors, 11 diagnoses were still considered candidates for bespoke ASO development. CONCLUSION: A meaningful proportion of genetic diagnoses identified by genome-wide sequencing may be amenable to ASO treatment. These results underscore the importance of timely diagnosis, and the proactive identification and accelerated functional testing of genetic variants amenable to ASO treatments.

Humans↗
PubMed2005

Changing educational paradigms in transfusion medicine and cellular therapies: development of a profession.

The transfusion medicine profession can be easily compared and contrasted with an early 1900 ironclad ship operating in the rough seas of the 21st century. Without modifying the old ship to today's standards, even the captain and crew will begin to expect the ship to meet its demise. The unfortunate passengers, on the other hand, do not expect that they are on an old obsolete ship and, instead, are innocent victims stuck on a doomed course. The old ironclad ship must change into a sleek cruiser and utilize the latest available technology so that its well-educated and competent captain and crew can safely navigate even the most challenging waters. The transfusion medicine profession must transform itself into a state-of-the-art ship so that it, like the refurbished ironclad ship, can be set on cruise control through the open seas. The question facing our industry is do we have the courage to utilize modern technology and to commit the funds necessary to develop, implement, and maintain our existence? It is difficult to plot a steady course into the future because of existing challenges that stand ready to sink our profession, including economic wrangling over regulation, technologic changes, generation conflict, and political differences that threaten our excellence. The primary purpose of this article is to focus on the educational needs that affect all personnel involved in transfusion medicine. In addition, this article will address potential adverse outcomes and investigate possible resolutions to avoid the "sinking ship." Within the next 5 to 7 years, without a corrective course of action, our profession will be at the bottom of the clinical ladder, remembered more for its demise and tragic ending than for its accomplishments. It is hoped, successful implementation of changes in educational paradigms in transfusion medicine may lead to a renaissance within our workforce-generations working together, each sharing and learning from one another.

Accreditation↗
PubMed1999

Willingness to pay for periodontal therapy: development and testing of an instrument.

OBJECTIVES: The objective of this study was to develop and test the feasibility and validity of a willingness to pay (WTP) tool in a dental setting. METHODS: A questionnaire measured individuals' preferences among alternative treatments for periodontal disease and the maximum they would be willing to pay for their treatment of choice in terms of dental insurance premiums. The questionnaire provides detailed information, in probabilistic terms, of the risks and benefits of treatment choices for moderate to advanced adult periodontitis. It was pilot tested on 23 periodontal patients and 18 dental school faculty and staff. RESULTS: The majority (92.6%) felt the questionnaire was an accurate representation of treatments and outcomes, establishing face and content validity. In terms of construct validity, four hypotheses were tested: (1) manipulation of the outcomes of the preferred treatment led to a predictable shift in preferences for 38 subjects (92.7%); (2) although periodontal patients were not more likely to choose periodontal surgery than nonpatients (P = .14), those with a history of surgery were more likely to choose surgery again (P = .06); (3) WTP was positively related to income level (P = .05); and (4) subjects were willing to pay more for coverage for themselves than for others. Periodontal surgery was the preferred treatment for moderate to advanced periodontal disease, and was more strongly preferred than other choices (i.e., a higher WTP) for all income groups. The intraclass correlation coefficient for treatment preferences was 0.95 (P < .001) and the kappa for WTP was 0.78 (P < .001). CONCLUSION: This pilot study supports some of the criteria concerning validity of the WTP questionnaire to measure preferences for alternative periodontal therapies. Further testing on larger samples is required to confirm these results.

Adult↗
PubMed2001

[New therapy developments in rheumatoid arthritis].

Despite the anti-TNF alpha based progress in the treatment of RA, it is necessary to further optimize study designs and reports (Etanercept/MTX combination with results of radiological progression; publication of D2E7 trials; combination of D2E7 with MTX). Moreover, innovative immunobiologicals (PEG-TNFRI, PEG-TNF alpha antibody fragments, soluble TNFRI, CTLA4-Ig, CD40 ligand antibody, antibodies against IFN-gamma, IL-6, IL-12, IL-15, IL-18, complements), inhibitors of TNF alpha translation (peptides, anti-sense constructs) or TNF alpha synthesis (targeting NF kappa B, p38 MAP-kinase, phosphodiesterase IV, TNF alpha converting enzyme) are forthcoming. Principally different are inhibitors of complement convertases or collagenase as well as vaccination studies or trials trying to induce T cell anergy. Furthermore, for patients with MTX side effects, alternative DMARDs need to be tested along with TNF alpha blockers. Combination studies of TNF alpha constructs with other immunobiologicals (anti-CD4, IL-4, IL-10, IL-1RA) should be evaluated. To date, TNF alpha blockers have been evaluated in very early RA. Finally, a step-down trial will test whether--after induction of remission with a TNF alpha blocker plus MTX--replacement of the TNF alpha blocker with MTX alone or in combination with leflunomide will be able to keep disease activity suppressed for a longer duration.

Antirheumatic Agents↗
PubMed2002

Mitochondrial damage in patients with long-term corticosteroid therapy: development of oculoskeletal symptoms similar to mitochondrial disease.

Two patients with long-term corticosteroid administration sporadically developed limb muscle wasting followed by ophthalmoplegia, and the skeletal muscle pathology revealed ragged-red fibers (RRFs) with abnormal mitochondria, in addition to the findings of corticosteroid myopathy. The oculoskeletal symptoms of the present cases resemble those of chronic progressive external ophthalmoplegia, a type of mitochondrial disease. The ocular muscles have more RRFs than limb muscles, and large multiple deletions of mitochondrial DNA was detected in ocular and limb muscles of the two patients by PCR but not by Southern blotting. Immunohistochemistry demonstrated that 8-hydroxy-deoxyguanosine (8-OH-dG) and 4-hydroxy-2-nonenal were intensely stained in skeletal muscles of these patients particularly in RRFs. High-performance liquid chromatography with electrochemical detection analysis revealed an increase in 8-OH-dG from mitochondrial DNA. These findings may suggest that long-term corticosteroid administration potentially induces oxidative stress-mediated mitochondrial damage, resulting in the development of the oculoskeletal symptoms in some patients.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

[Therapeutic concepts and therapy development in the framework of longterm treatment of victims of sexual and domestic violence].

Domestic violence differs from the nonrecurring trauma e.g. in the context of rape by a stranger in different aspects, emphasising the complexity of the victim's reaction and the enmeshment of the perpetrator The violence takes place in an established system of an intimate relationship which the woman was contracting voluntarily. Violence happens repeatedly and often several individuals (partner, children are directly and indirectly involved, which abide a relationship with the perpetrator Therefore the treatment of the posttraumatic stress disorder outstands in several aspects. The victims initially shows difficulties in talking about the experienced violence and are afraid to become unloyal; a therapeutic approach is often possible only after a fairly long time. Most authors agree that trauma therap the three phases (1 security and protection, psychoeducation and stabilisation, (2 trauma confrontation and (3 reintegration. Establishing a secure environment and intrapsychic stabilisation are a requirement for the therapeutic confrontation with the traumata in order to avoid re-traumatisation. Working with domestic violence victims is complex and demanding, experience in the work with trauma victims and regular supervision are fundamental.

Adolescent↗