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PubMed2003

Developing an integrative therapies program in a tertiary care cardiovascular hospital.

This article describes one hospital's approach to developing an inpatient integrative therapies program and the foundation for a broader integrative healthcare vision. Since the program's inception, additional evidence has accumulated in the literature supporting the impact of integrative therapies strategies on patients' quality of life during inpatient stays. These findings and our own evaluation processes have encouraged continued program growth. Several elements were critical to the program's success. Review of the literature and investigation of other programs served as preparation before the actual program started. It was necessary to have administrative, nursing, and physician champions who were able to envision the program and see the value of this approach for patients. We appreciated the need for evidence-based outcomes research and demonstrable patient outcomes. Finally, a program manager was hired who was able to understand the culture of the hospital and the organizational change process. Each of these basic steps, which called for interdisciplinary collaboration, allowed us to accomplish the goal of using integrative therapies as adjuncts to conventional medical care and thereby supported an integrative approach. Consistently linking the integrative vision to patient needs and requirements helped us to identify many new avenues to expand upon this work. The process of program development described may be useful to other inpatient cardiovascular programs inclusive of critical care settings. Adaptations of our experience to other populations in critical care and across other hospital settings may be possible.

Cardiac Care Facilities↗
PubMed1994

Complications of spinal opioid therapy: myoclonus, spastic muscle tone and spinal jerking.

This study was made in order to define risk factors for patients requiring spinal opioid therapy developing painful spastic muscle tone together with myoclonus and spinal jerking (MSJ). The case histories of 75 patients, all receiving morphine spinally, were retrospectively analysed and, of these, 10 suffered from the MSJ syndrome. The following were taken as evaluation criteria: age, sex, performance status, duration and dosage of previous systemic and current spinal morphine therapy, concomitant analgesic and co-analgesic medication, pretreatment of the dorsal column and neurological dysfunction due to damage either of the nerval plexus or of the medulla spinalis. As a result, high spinal morphine doses in conjunction with pathological changes within the spine were shown to be risk factors for this syndrome. Changing from spinal to systemic morphine application or reduction of spinal doses together with the addition of systemic morphine led to complete recovery from MSJ. As underlying mechanism, an imbalance between the activity of spinal and central opioid receptors and/or toxic morphine effects on the medulla spinalis are discussed. In conclusion, great care should be taken when applying morphine to the spine in patients with neurological dysfunction due to an apparent pathology of the medulla spinalis, especially if large amounts of morphine are likely to be required. Some systemic application of morphine might reduce the risk of patients developing MSJ syndrome.

Administration, Oral↗
PubMed2002

Overtreatment in children with epilepsy.

Children with epilepsy are at risk for overtreatment, defined as the use of an excessive number or amount of antiepiletic drugs (AEDs). While the extent of overtreatment of epilepsy in children is not known, there is increasing awareness that overtreatment with AEDs contributes to the morbidity associated with childhood epilepsy. Reasons for overtreatment include using AEDs in a child with seizures who does not require therapy, choosing an inappropriate AED for the seizure type or syndrome; treating non-epileptic behaviors as seizures, use of polytherapy when monotherapy would suffice, and inadequate therapeutic options. Despite the introduction of eight new AEDs in the United States during the last decade, many children continue to be treated with the older generation sedative AEDs. Numerous investigators have now demonstrated that sedative AEDs can be safely removed from the drug regimen of children with epilepsy with resultant improvement in behavior, alertness, and improved seizure control. However, the biggest obstacle to overtreatment is the lack of effective therapies for many of the childhood epileptic syndromes. Until there are more effective therapies developed it is highly likely that children will continue to be over-medicated on ineffective and detrimental AEDs.

Adolescent↗
PubMed2003

[A case of chronic pouchitis resistant to medical treatment].

Pouchitis, a non-specific acute inflammation occurring in the ileal pouch, is one of the most common complications developed after the restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) performed for the treatment for the patients with ulcerative colitis and familial adenomatous polyposis. The prevalence of pouchitis is known to range from 20% to 50%. One to two percent of the cases are chronic and resistant to the drug therapy. The effective treatment for this chronic resistant pouchitis is to remove the ileal pouch and perform the permanent ileostomy. Hereby, we report one case of chronic pouchitis resistant to multiple drug therapy developed after IPAA performed for the treatment of ulcerative colitis in a patient.

Chronic Disease↗
PubMed1990

[The value of radiotherapy in the treatment of tympano-jugulare chemodectoma. Apropos of 18 cases].

Surgery is the standard treatment of tympano-jugular chemodectomas. Radiation therapy is used only for inoperable forms. Since the tumor most often does not regress completely after irradiation, radiation therapy is generally considered as palliative. From 1979 to 1988, 18 patients with this rare tumor were referred to the Necker Hospital Tumor Center for radiation therapy. These patients have now been followed for 2 to 11 years. Tumors were extensive (Fish Stage C and D) in 75% of the patients and half of these patients showed cranial nerve involvement in addition to the usual otovestibular anomalies. Three patients were referred for recurrent tumors and 7 patients had undergone surgery just prior to radiation therapy. Among the 11 patients treated with the tumor in place, 7 had more or less complete regression of symptoms and radiologic signs, 3 had no further progression of symptoms and radiologic signs and 1 had tumor progression and expired as the result of the disease. No patient receiving post-operative radiation therapy developed clinical or radiological evidence of recurrent tumor. Among the 18 patients treated, 2 died of intercurrent disease. Our experience shows that a dose of 45 Gy is suffisant, leaves no trace, and does not prevent subsequent surgery. In an extensive review of the literature, tumor growth stopped or regressed after radiation therapy in 90% of the patients reported. Therefore, if incomplete surgery or neurological operative sequelae seem unavoidable, we prefer radiation therapy to surgical management of this tumor.

Adult↗
PubMed1995

Our bodies, our selves: treating the somatic expressions of trauma with ego-state therapy.

Trauma activates primitive defenses which often involve somatic processes. In this paper, the author explores the use of somatic approaches to ego-state therapy, developed by John and Helen Watkins (1979), which has been shown in the literature to be an effective method of treating the internal fragmentation and dissociated response patterns related to early childhood trauma. Through the use of hypnotic techniques such as the somatic bridge, ideosensory signalling, and sensory awareness training, ego-state therapy can be directed to those parts of the self which are more connected to somatic expressions of traumatic experiences. Several clinical case examples are presented to illustrate the potential of this approach in the treatment of trauma. Specific benefits for patients who complain of psychosomatic symptoms are discussed, as well as for those with compromised body image and perception, and its usefulness as a hypnoanalytic tool for uncovering memories that may be more somatically based.

Adult↗
PubMed1980

Multi-level couple therapy: applying a metacommunicational framework of couple interactions.

Excerpts from a couple therapy case are cited to illustrate the practical significance of a multi-level framework in understanding couple interactions. The clinical implications of the metacommunicational framework, as a metaphor for examining and understanding relational processes, are discussed. Also, the pragmatics of following "process" at a variety of levels when working with punctuational differences, developing therapy strategies and goals, and measuring the progress of couple therapy are discussed.

Accidents↗
PubMed2005

Coincidence planar imaging for dynamic [18F]FDG uptake in nude mice with tumors and inflammation: correlated with histopathology and micro-autoradiography.

The Institute of Nuclear Energy Research of Taiwan has developed a dynamic coincidence detection device for positron emitted radiotracer pharmacodynamic study in small mice models. In this study, we set up an experimental paradigm by determining [fluorine-18]-2-deoxy-2-fluoro-D-glucose ([18F]FDG) dynamic uptake in tumors and inflammations in nude mice as the foundation for future applications in therapy development. Histopathology and micro-autoradiography of these tumors and inflammations were obtained for confirmation. Dynamic coincidence planar images of six tumors and two inflammations in nude mice were acquired over 4 hours immediately after injection of 25.9 MBq of [18F]FDG into the right thigh of each animal. After image reconstruction, the lesion-to-background ratios were calculated in regions of interest over the lesion and contralateral thigh to determine the equilibrium status of the radiotracer. All mice were sacrificed for histopathologic examination and six of the mice were examined with micro-autoradiography. [18F]FDG uptake in tumors and inflammations both reached equilibrium about 3 hours after injection. At equilibrium, [18F]FDG uptake into tumors was two to four times higher than the background. Uptake into the 4-day and 8-day inflammations was 2.3 and 5.5 times higher than the background, respectively. Histopathology showed macrophage and neutrophil infiltration around the tumors and in the inflammations. Micro-autoradiography showed dense silver grains in the granulation tissue surrounding the tumors and inflammations. The preliminary results suggested that dynamic [18F]FDG coincidence planar imaging can help in determining the suitable time for static [18F]FDG imaging in nude mice models. The optimal time for static [18F]FDG positron emission tomography imaging was around 3 hours after injection. The paradigm for determining a dynamic [18F]FDG uptake pattern was demonstrated for future new therapeutic drug experimental use.

Animals↗
PubMed2026

Acbd7 is essential for preserving hair cell-mediated auditory and vestibular function.

Understanding the molecular basis of hair cell function is essential for elucidating inner ear physiology and developing therapies for auditory-vestibular disorders. Here, we identify acyl-CoA binding domain-containing 7 (Acbd7) as a hair cell-specific gene critical for sensory maintenance. Single-cell transcriptomics of mouse cochlear organoids revealed Acbd7 as a top hair cell-enriched transcript, with its spatiotemporal expression confirmed from embryonic development through adulthood in both auditory and vestibular hair cells. Acbd7‑deficient mice exhibited pronounced hair cell degeneration, characterized by synaptic defects and diminished calcium currents in inner hair cells and loss of outer hair cells. Transcriptomic and proteomic analyses linked Acbd7 to the regulation of Ca2+ signaling and fatty acid metabolism pathways. Our findings establish Acbd7 as a critical regulator of Ca2+ homeostasis and functional integrity in hair cells, thereby elucidating a key mechanism by which a fatty acid metabolism factor sustains hair cell function and providing potential therapeutic targets for inner ear disorders.

Animals↗
PubMedDate not supplied

Innovative immune-based therapeutic approaches for the treatment of type 1 diabetes mellitus.

Type 1 diabetes mellitus is an autoimmune disease caused by a culmination of noxious processes of autoimmunity composed of various components of the innate and adaptive immune systems. Current treatment of type 1 diabetes focuses on restraining the endocrine disease without affecting the autoimmune process that underlies it. Prevention of this disease requires immune modulation and early intervention. New therapeutic approaches can be classified on the basis of the immunological arm targeted, that is, T-cell immune modulation (using cytokines, anti-CD3 monoclonal antibodies, and peptide MHC class II dimers), innate immune system modulation (using alpha-galactosylceramide or peptide 277), or specific antigen vaccination (glutamic acid decarboxylase and insulin). Here we review the most promising therapies developed based on these targets and emphasize those that have reached human phase clinical investigation.

Animals↗
PubMedDate not supplied

Infliximab for the treatment of posterior uveitis with retinal neovascularization in Behçet disease.

PURPOSE: To report a case of posterior uveitis with retinal neovascularization in a patient with Behçet disease treated with infliximab. METHODS: A 50-year-old man with a history of recurrent relapses of ocular inflammation despite immunosuppressive therapy developed retinal neovascularization near the optic disk. The patient was treated with infliximab and followed up for 12 months. RESULTS: Retinal neovascularization regressed 8 months after the first anti-tumor necrosis factor (TNF) treatment and with six infusions of infliximab. The ocular inflammation resolved almost completely. CONCLUSIONS: The result suggests that anti-TNF therapy may be effective in the treatment of retinal neovascularization caused by panuveitis in Behçet disease.

Adult↗
PubMed1986

Long-term efficacy and safety of auranofin: a review of clinical experience.

Auranofin (AF) is the first oral gold therapy developed for the treatment of rheumatoid arthritis (RA). Since the drug was introduced in 1982, more than 100,000 patients have been treated with AF. Controlled clinical trials prior to introduction included more than 5,000 patients, some of whom received AF for more than 7 years. At the recommended dose of 6 mg/day, AF therapy results in a lower total body burden of gold than does injectable gold (IG). However, comparative studies indicate that the clinical effect of AF is comparable to that of IG. Adverse events that occur during AF therapy tend to be mild and of short duration, often resolving with continued therapy or temporarily reduced dosage. Most adverse events occur during the first few months of therapy, and the incidence diminishes over time. Data on 134 patients who received AF for more than 5 years demonstrate a sustained therapeutic effect and no cumulative toxicity from long-term therapy. In 18 comparative trials, 1,053 patients with RA received either AF (527 patients) or IG (526 patients) for up to 36 months. At 1 year, similar proportions of patients in the AF and IG groups had 50% or greater improvement in various parameters of disease activity. Safety analysis showed that AF was significantly better tolerated than IG. The rate of withdrawal because of adverse events was about twice as great in the IG group as in the AF group, both at one year (14% vs. 31%, p less than 0.05) and for the duration of the trials (18% vs. 34%, p less than 0.05). This suggests that the benefit-to-risk ratio is more favorable with AF.

Administration, Oral↗
PubMed1996

Effects of diuretic therapy on the development of tolerance to nitroglycerin and exercise capacity in patients with chronic stable angina.

BACKGROUND: Therapy with diuretics has been reported to prevent the development of nitrate tolerance. Importantly, diuretics may have independent antianginal effects through their effects on intravascular volume. The present investigation was designed to determine whether diuretic therapy could prevent the development of tolerance to continuous transdermal nitroglycerin. The study was also designed to examine whether diuretic therapy has an independent antianginal effect. METHODS AND RESULTS: Twelve patients with chronic stable angina were studied in a randomized, double-blind, crossover trial. Patients received diuretic (hydrochlorothiazide plus amiloride) or placebo for 14 to 20 days. During each double-blind treatment period, patients underwent treadmill exercise testing on three separate occasions. The first exercise testing was performed after 7 to 10 days of single-blind, placebo transdermal nitroglycerin therapy. Subsequently, exercise testing was repeated on the first day of active transdermal nitroglycerin therapy and following 7 to 10 days of continuous transdermal nitroglycerin application. Therapy with a diuretic was associated with an increase in exercise capacity but had no effect on nitroglycerin tolerance. During therapy with placebo transdermal nitroglycerin, diuretic therapy caused an increase in treadmill walking time to the development of moderate angina compared with placebo (371 +/- 26 versus 288 +/- 16 seconds, diuretic versus placebo, P < .01). Similar results were obtained during both acute and sustained nitroglycerin therapy. CONCLUSIONS: The results of this study demonstrate that therapy with a diuretic has no effect on the development of tolerance to continuous transdermal nitroglycerin. Interestingly, diuretic therapy itself has important antianginal effects and improves exercise capacity in patients with stable angina.

Administration, Cutaneous↗
PubMed1995

Gene therapy in heart disease.

As the technology for gene therapy develops in vitro and in vivo in animal models, it is becoming clear that the three principal approaches--recombinant retroviruses, recombinant adenovirus, and direct DNA delivery--will ultimately have applications in specific therapeutic situations that take full advantage of the unique features of the specific delivery system: low level persistent expression after ex vivo recombinant retroviral therapy, high level transient expression after in vivo recombinant adenoviral therapy, or moderate level transient expression after in vivo administration of a synthetic DNA complex, which in principle could be repeated as desired.

Animals↗
PubMed1995

The effect of intensive diabetes therapy on the development and progression of neuropathy. The Diabetes Control and Complications Trial Research Group.

OBJECTIVE: To examine whether intensive therapy designed to achieve glycemic levels as close to normal as possible prevents or slows the progression of neuropathy when compared with conventional therapy in patients with insulin-dependent diabetes mellitus in the Diabetes Control and Complications Trial. DESIGN: Multicenter, randomized, controlled clinical trial. SETTING: 29 U.S. and Canadian clinical centers. PARTICIPANTS: 1441 patients aged 13 to 39 years, of whom 726 had had insulin-dependent diabetes mellitus for 1 to 5 years and had no retinopathy at baseline (primary prevention cohort); 715 had had diabetes for 1 to 15 years and had minimal to moderate nonproliferative retinopathy at baseline (secondary intervention cohort). INTERVENTION: Intensive therapy with three or more daily insulin injections or continuous subcutaneous insulin infusion guided by four or more glucose tests per day compared with conventional therapy with one or two daily insulin injections. RESULTS: Intensive therapy reduced the development of confirmed clinical neuropathy (defined as a history or physical examination consistent with clinical neuropathy confirmed by either abnormal nerve conduction or autonomic nervous system testing) by 64% (95% CI, 45% to 76%) in the combined cohorts after 5 years of follow-up (5% of the intensive therapy group compared with 13% of the conventional therapy group). The prevalence of abnormal nerve conduction and abnormal autonomic nervous system function were reduced by 44% (CI, 34% to 53%) and 53% (CI, 24% to 70%), respectively (26% of the intensive treatment group developed abnormal nerve conduction compared with 46% of the conventional treatment group; 4% of the intensive treatment group had abnormal autonomic nervous system function compared with 9% of the conventional treatment group). Finally, nerve conduction velocities generally remained stable with intensive therapy but decreased significantly with conventional therapy. CONCLUSION: Intensive diabetes therapy markedly delays or prevents the development of clinically manifest diabetic polyneuropathy as confirmed by objective nerve function testing in patients with insulin-dependent diabetes mellitus.

Adolescent↗
PubMed1999

A mutant streptokinase lacking the C-terminal 42 amino acids is less reactive with preexisting antibodies in patient sera.

Streptokinase (SK) is an efficacious thrombolytic drug for the treatment of myocardial infarction. Because of its immunogenicity, patients receiving SK therapy develop high anti-SK antibody (Ab) titers, which might provoke severe allergic reactions and neutralize SK activity. In this report we studied the reactivity of a synthetic 42-residue peptide resembling SKC-2 C-terminus with patient sera. SKC-2(373-414) peptide was recognized by 39 and 64% of patients, before and after SKC-2 therapy, respectively. An SKC-2 deletion mutant (mut-C42), lacking the same 42 C-terminal residues, was constructed and expressed in Escherichia coli. Recognition of mut-C42 by preexisting Abs from patient sera was 51 and 68% of reactivity to SKC-2, as assessed by direct binding and competition assays, respectively. For most of the patients, mut-C42-neutralizing activity titer (NAT) significantly decreased with respect to SKC-2-NAT. This study opens the possibility of producing a less immunogenic variant of SK, which could constitute a preferred alternative for thrombolytic therapy.

Allergens↗
PubMed2006

Cytokine polymorphisms influence treatment outcomes in SLE patients treated with antimalarial drugs.

Antimalarial agents have been widely used as disease-modifying antirheumatic drugs in the treatment of systemic lupus erythematosus (SLE) and other rheumatological diseases, although their mechanism of action has not yet been fully defined. It is known, however, that effective response to treatment is variable among patients. Thus, the identification of genetic predictors of treatment response would provide valuable information for therapeutic intervention. The aim of the present study was to analyze the effect of antimalarial treatment on tumor necrosis factor (TNF)alpha serum levels and evaluate the possible influence of TNFalpha and IL-10 functional genetic polymorphisms on the response to antimalarial drugs. To this end, TNFalpha serum levels were quantified in 171 SLE patients and 215 healthy controls by ELISA techniques and polymorphisms at positions -1,082 and -308 of the IL-10 and TNFalpha gene promoters were determined by PCR amplification followed by hybridization with fluorescent-labeled allele-specific probes in 192 SLE patients and 343 matched controls. Data were related to clinical features and treatment at the time of sampling and during the course of the disease. Results showed a significantly higher amount of serum TNFalpha in the entire SLE population compared with controls. However, TNFalpha serum levels correlated negatively with the use of antimalarial treatment during at least three months before sampling. Patients under single or combined treatment with these drugs had TNFalpha serum levels similar to healthy controls, whereas untreated patients and those under corticosteroid or immunosuppressive therapies had increased amounts of this cytokine. This suggests, however, that antimalarial-mediated inhibition of TNFalpha was only significant in patients who were genetically high TNFalpha or low IL-10 producers. In addition, evaluation of SLE patients administered antimalarial drugs for three or more years who did not require any other specific SLE treatment indicates that patients with the combined genotype low IL-10/high TNFalpha are the best responders to antimalarial therapy, developing mild disease with a good course under this treatment. In conclusion, we proposed that an antimalarial-mediated downregulation of TNFalpha levels in SLE patients is influenced by polymorphisms at IL-10 and TNFalpha promoters. Our results may thus find important clinical application through the identification of patients who are the most likely to benefit from antimalarial therapy.

Adult↗
PubMed1998

[Antitumor effect of combined therapy with adenovirus-mediated CD suicide gene and interleukin 2 gene transfer and its immunological mechanism].

OBJECTIVE: Adenovirus harboring E. coli cytosine deaminase gene(AdCD) and adenovirus harboring interleukin 2 gene (AdIL-2) were used for the combined treatment of established tumors in vivo. METHODS: C57BL/6 mice were inoculated with B16F10 melanoma cells and 3 days later received at the tumor site injections of AdCD and/or AdIL-2 followed by i.p. injection of 5-fluorocytosine (5-Fc) 300 mg/kg per day for 10 days. RESULTS: Mice received combined therapy developed tumors more slowly and survived much longer when compared with mice treated with AdCD/5-Fc, AdIL-2, control adenovirus AdlacZ/5-FC, or PBS. To investigate the immunological mechanism of the antitumor effects of the combined treatment it was found to induce enhanced natural killer cell activity and specific cytotoxic T cell activity. FACS analysis demonstrated that AdIL-2/AdCD/5-Fc therapy increased the expression of H-2Kb and B7-1 on freshly isolated tumor cells. The CD4+ and CD8+ T cell infiltration in the tumor increased significantly. CONCLUSION: Transfer of CD suicide gene plus 5-Fc combined with transfer of IL-2 gene synergistically inhibits the growth of melanoma in mice. Besides the cytotoxic effect of 5-Fc, specific and non-specific antitumor immunity might be responsible for the therapeutic effect. The combined therapy might have therapeutic potentials for human cancer.

Adenoviridae↗