The Therapeutic Relationship and Cognitive Behavioural Therapy: A Case Study of an Adolescent Girl With Depression

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Cheryl Joy Easterbrook

2017-02-01

Full Text Available The therapeutic relationship in Cognitive Behavioural Therapy (CBT has been argued to play an essential role in positive outcomes in therapy. However, it is described as necessary and yet, secondary to technique, often receiving little attention in the training of CBT therapists. This case study explores a trainee psychologist’s experience of finding difficulty in feeling authentic and the application of CBT techniques with her client. This difficulty informed the research question; what is the value of the therapeutic relationship in CBT? A hermeneutic approach with a strong emphasis on phenomenology, is used to explore the therapeutic process and the therapeutic relationship that developed between therapist and client. Qualitative descriptions of 11 sessions are divided into themes, these are discussed in relation to what happened in therapy, and are then discussed further regarding discovery and process into the therapeutic relationship. Conclusions from this case study could possibly reveal the value of the therapeutic relationship when working from a CBT approach, and how it seemed to enable the client to achieve her goal in therapy.

Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications.

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Fasano, Alessio

2012-10-01

One of the most important and overlooked functions of the gastrointestinal tract is to provide a dynamic barrier to tightly controlled antigen trafficking through both the transcellular and paracellular pathways. Intercellular tight junctions (TJ) are the key structures regulating paracellular trafficking of macromolecules. Although steady progress has been made in understanding TJ ultrastructure, relatively little is known about their pathophysiological regulation. Our discovery of zonulin, the only known physiological modulator of intercellular TJ described so far, increased understanding of the intricate mechanisms that regulate gut permeability and led us to appreciate that its up-regulation in genetically susceptible individuals may lead to immune-mediated diseases. This information has translational implications, because the zonulin pathway is currently exploited to develop both diagnostic and therapeutic applications pertinent to a variety of immune-mediated diseases. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Nosocomial septicemia and therapeutic angiography. Report of four cases

International Nuclear Information System (INIS)

Meyer, Ph.; Reizine, D.; Merland, J.J.; Guerin, J.M.

1988-01-01

Therapeutic angiography may be responsible for rare, but serious infectious complications.The authors report 4 cases occurring immediately following angiography. Three modes of contamination are proposed. Contamination by material used during the angiography is due to multiresistant hospital organisms. Penetration of cutaneous organisms into the circulation from the puncture site and bacterial contamination of a focus of tissue necrosis distal to the embolisation explain the other cases. Curative treatment is difficult because of the possibility of contamination of the embolisation material. Prophylactic treatment is essential and consists of respect of the rules of surgical asepsis, bacteriological control of the fluids used and eradication of adjacent septic foci. Routine antibiotic prophylaxis has yet to be evaluated [fr

Is Spinal Muscular Atrophy a disease of the motor neurons only: pathogenesis and therapeutic implications?

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Simone, Chiara; Ramirez, Agnese; Bucchia, Monica; Rinchetti, Paola; Rideout, Hardy; Papadimitriou, Dimitra; Re, Diane B.; Corti, Stefania

2016-01-01

Spinal Muscular Atrophy (SMA) is a genetic neurological disease that causes infant mortality; no effective therapies are currently available. SMA is due to homozygous mutations and/or deletions in the Survival Motor Neuron 1 (SMN1) gene and subsequent reduction of the SMN protein, leading to the death of motor neurons. However, there is increasing evidence that in addition to motor neurons, other cell types are contributing to SMA pathology. In this review, we will discuss the involvement of non-motor neuronal cells, located both inside and outside the central nervous system, in disease onset and progression. These contribution of non-motor neuronal cells to disease pathogenesis has important therapeutic implications: in fact, even if SMN restoration in motor neurons is needed, it has been shown that optimal phenotypic amelioration in animal models of SMA requires a more widespread SMN correction. It will be crucial to take this evidence into account before clinical translation of the novel therapeutic approaches that are currently under development. PMID:26681261

Current and novel insights into the neurophysiology of migraine and its implications for therapeutics.

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Akerman, Simon; Romero-Reyes, Marcela; Holland, Philip R

2017-04-01

Migraine headache and its associated symptoms have plagued humans for two millennia. It is manifest throughout the world, and affects more than 1/6 of the global population. It is the most common brain disorder, and is characterized by moderate to severe unilateral headache that is accompanied by vomiting, nausea, photophobia, phonophobia, and other hypersensitive symptoms of the senses. While there is still a clear lack of understanding of its neurophysiology, it is beginning to be understood, and it seems to suggest migraine is a disorder of brain sensory processing, characterized by a generalized neuronal hyperexcitability. The complex symptomatology of migraine indicates that multiple neuronal systems are involved, including brainstem and diencephalic systems, which function abnormally, resulting in premonitory symptoms, ultimately evolving to affect the dural trigeminovascular system, and the pain phase of migraine. The migraineur also seems to be particularly sensitive to fluctuations in homeostasis, such as sleep, feeding and stress, reflecting the abnormality of functioning in these brainstem and diencephalic systems. Implications for therapeutic development have grown out of our understanding of migraine neurophysiology, leading to major drug classes, such as triptans, calcitonin gene-related peptide receptor antagonists, and 5-HT 1F receptor agonists, as well as neuromodulatory approaches, with the promise of more to come. The present review will discuss the current understanding of the neurophysiology of migraine, particularly migraine headache, and novel insights into the complex neural networks responsible for associated neurological symptoms, and how interaction of these networks with migraine pain pathways has implications for the development of novel therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

Genital piercings: diagnostic and therapeutic implications for urologists.

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Nelius, Thomas; Armstrong, Myrna L; Rinard, Katherine; Young, Cathy; Hogan, LaMicha; Angel, Elayne

2011-11-01

To provide quantitative and qualitative data that will assist evidence-based decision making for men and women with genital piercings (GP) when they present to urologists in ambulatory clinics or office settings. Currently many persons with GP seek nonmedical advice. A comprehensive 35-year (1975-2010) longitudinal electronic literature search (MEDLINE, EMBASE, CINAHL, OVID) was conducted for all relevant articles discussing GP. Authors of general body art literature tended to project many GP complications with potential statements of concern, drawing in overall piercings problems; then the information was further replicated. Few studies regarding GP clinical implications were located and more GP assumptions were noted. Only 17 cases, over 17 years, describe specific complications in the peer-reviewed literature, mainly from international sources (75%), and mostly with "Prince Albert" piercings (65%). Three cross-sectional studies provided further self-reported data. Persons with GP still remain a hidden variable so no baseline figures assess the overall GP picture, but this review did gather more evidence about GP wearers and should stimulate further research, rather than collectively projecting general body piercing information onto those with GP. With an increase in GP, urologists need to know the specific differences, medical implications, significant short- and long-term health risks, and patients concerns to treat and counsel patients in a culturally sensitive manner. Targeted educational strategies should be developed. Considering the amount of body modification, including GP, better legislation for public safety is overdue. Copyright © 2011 Elsevier Inc. All rights reserved.

Case formulation and the therapeutic relationship: the role of therapist self-reflection and self-revelation.

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Tufekcioglu, Sumru; Muran, J Christopher

2015-05-01

This article examines the role of the therapist's self-reflection and self-revelation in case formulation. We believe that a collaboratively constructed case formulation must always be considered in the context of an evolving therapeutic relationship. Further, self-reflection and self-revelation on the part of the therapist are critical for a more elaborate and nuanced case formulation and for understanding the patient. This highlights the importance of attunement to the here and now and the evolving therapeutic relationship. From this attunement, the therapist's self-reflection and self-revelation can emerge further, which can lead to the patient's personal growth and increased self-other awareness. To illustrate our point, we present an integrative, relational model in the case of a patient who has been in treatment. © 2015 Wiley Periodicals, Inc.

Coronary microvasculopathy in heart transplantation: Consequences and therapeutic implications.

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Vecchiati, Alessandra; Tellatin, Sara; Angelini, Annalisa; Iliceto, Sabino; Tona, Francesco

2014-06-24

Despite the progress made in the prevention and treatment of rejection of the transplanted heart, cardiac allograft vasculopathy (CAV) remains the main cause of death in late survival transplanted patients. CAV consists of a progressive diffuse intimal hyperplasia and the proliferation of vascular smooth muscle cells, ending in wall thickening of epicardial vessels, intramyocardial arteries (50-20 μm), arterioles (20-10 μm), and capillaries (system. The non-immunological factors are older donor age, ischemia-reperfusion time, hyperlipidemia and CMV infections. Diagnostic techniques that are able to assess microvascular function are lacking. Intravascular ultrasound and fractional flow reserve, when performed during coronary angiography, are able to detect epicardial coronary artery disease but are not sensitive enough to assess microvascular changes. Some authors have proposed an index of microcirculatory resistance during maximal hyperemia, which is calculated by dividing pressure by flow (distal pressure multiplied by the hyperemic mean transit time). Non-invasive methods to assess coronary physiology are stress echocardiography, coronary flow reserve by transthoracic Doppler echocardiography, single photon emission computed tomography, and perfusion cardiac magnetic resonance. In this review, we intend to analyze the mechanisms, consequences and therapeutic implications of microvascular dysfunction, including an extended citation of relevant literature data.

Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications

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HuaLin Cai

2018-03-01

Full Text Available Neurosteroids are a group of important endogenous molecules affecting many neural functions in the brain. Increasing evidence suggests a possible role of these neurosteroids in the pathology and symptomatology of schizophrenia (SZ and other mental disorders. The aim of this review is to summarize the current knowledge about the neural functions of neurosteroids in the brain, and to evaluate the role of the key neurosteroids as candidate modulators in the etiology and therapeutics of SZ. The present paper provides a brief introduction of neurosteroid metabolism and distribution, followed by a discussion of the mechanisms underlying neurosteroid actions in the brain. The content regarding the modulation of the GABAA receptor is elaborated, given the considerable knowledge of its interactions with other neurotransmitter and neuroprotective systems, as well as its ameliorating effects on stress that may play a role in the SZ pathophysiology. In addition, several preclinical and clinical studies suggested a therapeutic benefit of neurosteroids in SZ patients, even though the presence of altered neurosteroid pathways in the circulating blood and/or brain remains debatable. Following treatment of antipsychotic drugs in SZ, therapeutic benefits have also been linked to the regulation of neurosteroid signaling. Specifically, the neurosteroids such as pregnenolone and dehydroepiandrosterone affect a broad spectrum of behavioral functions through their unique molecular characteristics and may represent innovative therapeutic targets for SZ. Future investigations in larger cohorts with long-term follow-ups will be required to ascertain the neuropsychopharmacological role of this yet unexploited class of neurosteroid agents.

Mechanisms and consequences of oxidative stress in lung disease: therapeutic implications for an aging populace.

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Hecker, Louise

2018-04-01

The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility. Here, we focus on three lung diseases for which aging is a significant risk factor: acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Preclinical and clinical development for redox- and senescence-altering therapeutic strategies are discussed, as well as scientific advancements that may direct current and future therapeutic development. A deeper understanding of how aging impacts normal lung function, redox balance, and injury-repair processes will inspire the development of new therapies to prevent and/or reverse age-associated pulmonary diseases, and ultimately increase health span and longevity. This review is intended to encourage basic, clinical, and translational research that will bridge knowledge gaps at the intersection of aging, oxidative stress, and lung disease to fuel the development of more effective therapeutic strategies for lung diseases that disproportionately afflict the elderly.

Tyrosine Kinase Receptor Landscape in Lung Cancer: Therapeutical Implications

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A. Quintanal-Villalonga

2016-01-01

Full Text Available Lung cancer is a heterogeneous disease responsible for the most cases of cancer-related deaths. The majority of patients are clinically diagnosed at advanced stages, with a poor survival rate. For this reason, the identification of oncodrivers and novel biomarkers is decisive for the future clinical management of this pathology. The rise of high throughput technologies popularly referred to as “omics” has accelerated the discovery of new biomarkers and drivers for this pathology. Within them, tyrosine kinase receptors (TKRs have proven to be of importance as diagnostic, prognostic, and predictive tools and, due to their molecular nature, as therapeutic targets. Along this review, the role of TKRs in the different lung cancer histologies, research on improvement of anti-TKR therapy, and the current approaches to manage anti-TKR resistance will be discussed.

Calcium Regulation of Hemorrhagic Fever Virus Budding: Mechanistic Implications for Host-Oriented Therapeutic Intervention.

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Ziying Han

2015-10-01

Full Text Available Hemorrhagic fever viruses, including the filoviruses (Ebola and Marburg and arenaviruses (Lassa and Junín viruses, are serious human pathogens for which there are currently no FDA approved therapeutics or vaccines. Importantly, transmission of these viruses, and specifically late steps of budding, critically depend upon host cell machinery. Consequently, strategies which target these mechanisms represent potential targets for broad spectrum host oriented therapeutics. An important cellular signal implicated previously in EBOV budding is calcium. Indeed, host cell calcium signals are increasingly being recognized to play a role in steps of entry, replication, and transmission for a range of viruses, but if and how filoviruses and arenaviruses mobilize calcium and the precise stage of virus transmission regulated by calcium have not been defined. Here we demonstrate that expression of matrix proteins from both filoviruses and arenaviruses triggers an increase in host cytoplasmic Ca2+ concentration by a mechanism that requires host Orai1 channels. Furthermore, we demonstrate that Orai1 regulates both VLP and infectious filovirus and arenavirus production and spread. Notably, suppression of the protein that triggers Orai activation (Stromal Interaction Molecule 1, STIM1 and genetic inactivation or pharmacological blockade of Orai1 channels inhibits VLP and infectious virus egress. These findings are highly significant as they expand our understanding of host mechanisms that may broadly control enveloped RNA virus budding, and they establish Orai and STIM1 as novel targets for broad-spectrum host-oriented therapeutics to combat these emerging BSL-4 pathogens and potentially other enveloped RNA viruses that bud via similar mechanisms.

Identifying Inconsistencies and Reporting Deficits in Therapeutic Massage and Bodywork (TMB) Case Reports Authored by TMB Practitioners: a TMB-Adapted CAse REport (CARE) Guidelines Audit Through 2014.

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Munk, Niki; Shue, Sarah; Freeland, Emilee; Ralston, Rick; Boulanger, Karen T

2016-09-01

Case reports are a fundamental tool through which therapeutic massage and bodywork (TMB) practitioners can inform research and impact their field by detailing the presentation, treatment, and follow-up of a single individual encountered in practice. Inconsistencies in case reporting limit their impact as fundamental sources of clinical evidence. Using the TMB-adapted CAse REport (CARE) guidelines, the current study sought to provide a rich description regarding the reporting quality of TMB practitioner authored TMB case reports in the literature. 1) Systematic identification of published, peer-reviewed TMB case reports authored by TMB practitioners following PRISMA recommendations; 2) audit development based on TMB-adapted CARE guidelines; 3) audit implementation; and 4) descriptive analysis of audit scores. Our search identified 977 articles and 35 met study inclusion criteria. On average, TMB case reports included approximately 58% of the total items identified as necessary by the TMB-adapted CARE guidelines. Introduction sections of case reports had the best item reporting (80% on average), while Case Presentation (54%) and Results (52%) sections scored moderately overall, with only 20% of necessary Practitioner Description items included on average. Audit scores revealed inconsistent abstract reporting and few audited case reports including client race (20%), perspective (26%), and occupation/activities (40%); practitioner practice setting (12%), training (12%), scope-of-practice (29%), and credentialing (20%); adverse events or lack thereof (17%); and some aspect of informed consent (34%). Treatment descriptor item reporting varied from high to low. Various implications of concern are discussed. The current audit and descriptive analysis highlight several reporting inconsistencies in TMB case reports prior to 2015. Reporting guidelines for case reports are important if standards for, and impact of, TMB case reports are desired. Adherence to reporting

Therapeutic High-Density Barium Enema in a Case of Presumed Diverticular Hemorrhage

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Nonthalee Pausawasdi

2011-02-01

Full Text Available Many patients with lower gastrointestinal bleeding do not have an identifiable source of bleeding at colonoscopy. A significant percentage of these patients will have recurrent bleeding. In many patients, the presence of multiple diverticula leads to a diagnosis of presumed diverticular bleeding. Current treatment options include therapeutic endoscopy, angiography, or surgical resection, all of which depend on the identification of the diverticular source of bleeding. This report describes a case of recurrent bleeding in an elderly patient with diverticula but no identifiable source treated successfully with barium impaction therapy. This therapeutic modality does not depend on the identification of the bleeding diverticular lesion and was well tolerated by our 86-year-old patient.

Pathogenesis of Graves' disease and therapeutic implications

International Nuclear Information System (INIS)

Seif, F.J.

1997-01-01

Graves' disease presents itself clinically mainly as hyperthyroidism and infiltrative ophthalmopathy and to a minimal extent also as dermopathy and acropachy. Autoimmune processes are the basic pathogenesis. Stimulating antibodies against the TSH receptor cause hyperthyroidism. Autoantibodies and autoreactive T lymphocytes against primarily thyroidal antigens cross-react with similar antigens of the eye muscles and orbital connective tissue, thus spreading the disease from the thyroid to the eyes. The therapeutic goal comprises not only the treatment of hyperthyroidism, but also the induction of a steady immuntolerance in order to minimize the irreversible damage to the eye. The therapeutic armamentarium is formed by antithyroid drugs, glucocorticoids, retrobulbar radition and thyroid ablation, either by nearly total thyroidectomy or by radioiodine. The different indications for both ablative procedures are discussed. (orig.) [de

[Post-therapeutic evolution and prognostic factors of intestinal lymphomas, Retrospective analysis of 42 cases].

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Sánchez-Fayos, M P; Hernández Guío, C; Rivas, M C; Outeiriño, J; González-Campos, C; Lobo, F

1993-12-01

To evaluate in retrospect the response to therapy and long-term evolution of a series of primitive intestinal lymphomas. The series was comprised of 42 patients diagnosed in our hospital during 1960-1962. The mean age was 34.5 years (range, 3-73), the M/F ratio was 21/21, and the histopathology distributes as follows: high grade (HG), 24 cases, low grade (LG), 12 cases, and mixed (LG/HG), 6 cases. B/T immunophenotype: 40/2. Staging: IE1,29 cases, IIE2-IV, 11 cases. The treatment applied in the series was classified in various types: ample surgical resection (aSR), 21 cases; partial surgical resection (pSR), 9 cases; abdominal radiation therapy (RT), 7 cases; monochemotherapy (MCT), 7 cases, and polychemotherapy (PCT), 28 cases. The correlation of clinicobiological variables with immediate response to treatment was evaluated by means of the chi square test, and the acturial post-therapeutic survival curves in accordance to the life tables, differences being calculated by the log rank test. Small intestine was the commonest site of involvement, 31 cases; ileocecal region, 7 cases; colon, 2 cases, and colon plus small intestine, 2 cases. Regardless of therapy type, complete remission (CR) was attained in 20 patients (47.5%), partial remission in 5; 11 cases were unresponsive (26.5%) and early death occurred in 6 instances (14.2%). The acturial post-therapeutic survival offered an 8-year expectancy of 47%. The correlation between immediate complete response and 16 clinico-biologic variables showed favourable significance for tumoral proliferation index (i.e., Pc10-positive cells studies. 2) Female sex, type of therapy, multifocal involvement, the need of emergency surgery and high LDH levels have significant value in univariate analyses.

Recent Advances in Developing Inhibitors for Hypoxia-Inducible Factor Prolyl Hydroxylases and Their Therapeutic Implications

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So Yeon Kim

2015-11-01

Full Text Available Hypoxia-inducible factor (HIF prolyl hydroxylases (PHDs are members of the 2-oxoglutarate dependent non-heme iron dioxygenases. Due to their physiological roles in regulation of HIF-1α stability, many efforts have been focused on searching for selective PHD inhibitors to control HIF-1α levels for therapeutic applications. In this review, we first describe the structure of PHD2 as a molecular basis for structure-based drug design (SBDD and various experimental methods developed for measuring PHD activity. We further discuss the current status of the development of PHD inhibitors enabled by combining SBDD approaches with high-throughput screening. Finally, we highlight the clinical implications of small molecule PHD inhibitors.

Generalised pustular psoriasis – a case report and review of therapeutic approaches

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Agnieszka Osmola-Mańkowska

2014-11-01

Full Text Available Introduction. Generalised pustular psoriasis (GPP is regarded as a rare clinical subtype of psoriasis. The severity of GPP varies from a benign, chronic course to severe and widespread, life-threatening disease. Due to the uncommon nature of GPP, establishing treatment guidelines for this variant of psoriasis is challenging. Objective. To present the case of a patient with GPP with a short review of therapeutic approaches. Case report. Our patient was treated with standard methods such as acitretin, then cyclosporine and methotrexate as well as with biologic drug – infliximab. During the last and the most severe flare, combination therapy with systemic retinoid and PUVA (Re-PUVA was used. Conclusions. The treatment in GPP should be determined individually according to the severity of the disease, age, gender and comorbidities, as well as according to the physician’s experience with particular methods and their side effects. In addition, the availability of therapeutic options should be taken into consideration.

An unusual case of hypothermia associated with therapeutic doses of olanzapine: a case report

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Ratnayake Shiroma L

2011-05-01

Full Text Available Abstract Introduction We report a case of a 42-year-old man who had symptomatic hypothermia as a result of taking olanzapine for paranoid schizophrenia. According to published data, only a few cases of hypothermia associated with olanzapine have been reported since its introduction into clinical use. Case presentation A 42-year-old Sri Lankan man with schizophrenia who was being treated with a therapeutic dose of olanzapine presented with reduced level of consciousness. He had a core temperature of 32°C and was bradycardic. At the time of admission, the electrocardiogram showed sinus bradycardia with J waves. He did not have any risk factors for developing hypothermia except the use of olanzapine. There was improvement in his clinical condition with reversal of electrocardiogram changes following gradual rewarming and the omission of olanzapine. Conclusion Hypothermia induced by antipsychotic medications is not uncommon, but olanzapine-induced hypothermia is rare and occurrence has been reported during initiation or increasing the dose. But here the patient developed hypothermia without dose adjustment.

DAF as a therapeutic target for steroid hormones: implications for host-pathogen interactions.

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Nowicki, Bogdan; Nowicki, Stella

2013-01-01

In this chapter, we present a concise historic prospective and a summary of accumulated knowledge on steroid hormones, DAF expression, and therapeutic implication of steroid hormone treatment on multiple pathologies, including infection and the host-pathogen interactions. DAF/CD55 plays multiple physiologic functions including tissue protection from the cytotoxic complement injury, an anti-inflammatory function due to its anti-adherence properties which enhance transmigration of monocytes and macrophages and reduce tissue injury. DAF physiologic functions are essential in many organ systems including pregnancy for protection of the semiallogeneic fetus or for preventing uncontrolled infiltration by white cells in their pro- and/or anti-inflammatory functions. DAF expression appears to have multiple regulatory tissue-specific and/or menstrual cycle-specific mechanisms, which involve complex signaling mechanisms. Regulation of DAF expression may involve a direct or an indirect effect of at least the estrogen, progesterone, and corticosteroid regulatory pathways. DAF is exploited in multiple pathologic conditions by pathogens and viruses in chronic tissue infection processes. The binding of Escherichia coli bearing Dr adhesins to the DAF/CD55 receptor is DAF density dependent and triggers internalization of E. coli via an endocytic pathway involving CD55, lipid rafts, and microtubules. Dr+ E. coli or Dr antigen may persist in vivo in the interstitium for several months. Further understanding of such processes should be instrumental in designing therapeutic strategies for multiple conditions involving DAF's protective or pathologic functions and tailoring host expression of DAF.

Clinical impact of laboratory error on therapeutic drug monitoring of once-daily tobramycin in cystic fibrosis: Case series

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William A Prescott

2014-01-01

Full Text Available Once-daily dosing intravenous tobramycin is commonly used to treat cystic fibrosis pulmonary exacerbations. Clinicians often utilize historical therapeutic drug monitoring data to individualize the dose among patients who have been treated with tobramycin previously. This case series involves three patients with cystic fibrosis who had supra-therapeutic tobramycin levels despite use of a once-daily dosing that produced therapeutic drug levels during a previous hospital admission, raising questions about the validity of these levels. Investigation into several potential sources of error led to the discovery of an analyzer error in the laboratory. Once the laboratory’s tobramycin analyzer was recalibrated, the reported levels were comparable to historical levels. This case series emphasizes the clinical importance of critically analyzing reported levels, and specifically, the importance of utilizing past therapeutic drug monitoring data, if available, for all patients treated with intravenous tobramycin. If a patient was therapeutic on a similar dose of tobramycin during a previous admission, a dose adjustment may not be necessary, and clinicians should consider repeating levels while pursuing alternative explanations for the discrepant serum levels.

Pharmacogenomics and migraine: possible implications

DEFF Research Database (Denmark)

Tfelt-Hansen, P.; Brosen, K.

2008-01-01

Pharmacogenomics is the science about how inherited factors influence the effects of drugs. Drug response is always a result of mutually interacting genes with important modifications from environmental and constitutional factors. Based on the genetic variability of pharmacokinetic and in some...... cases pharmacodynamic variability we mention possible implications for the acute and preventive treatment of migraine. Pharmacogenomics will most likely in the future be one part of our therapeutic armamentarium and will provide a stronger scientific basis for optimizing drug therapy on the basis...

Oocyte activation and phospholipase C zeta (PLCζ: diagnostic and therapeutic implications for assisted reproductive technology

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Ramadan Walaa M

2012-07-01

Full Text Available Abstract Infertility affects one in seven couples globally and has recently been classified as a disease by the World Health Organisation (WHO. While in-vitro fertilisation (IVF offers effective treatment for many infertile couples, cases exhibiting severe male infertility (19–57% often remain difficult, if not impossible to treat. In such cases, intracytoplasmic sperm injection (ICSI, a technique in which a single sperm is microinjected into the oocyte, is implemented. However, 1–5% of ICSI cycles still fail to fertilise, affecting over 1000 couples per year in the UK alone. Pregnancy and delivery rates for IVF and ICSI rarely exceed 30% and 23% respectively. It is therefore imperative that Assisted Reproductive Technology (ART protocols are constantly modified by associated research programmes, in order to provide patients with the best chances of conception. Prior to fertilisation, mature oocytes are arrested in the metaphase stage of the second meiotic division (MII, which must be alleviated to allow the cell cycle, and subsequent embryogenesis, to proceed. Alleviation occurs through a series of concurrent events, collectively termed ‘oocyte activation’. In mammals, oocytes are activated by a series of intracellular calcium (Ca2+ oscillations following gamete fusion. Recent evidence implicates a sperm-specific phospholipase C, PLCzeta (PLCζ, introduced into the oocyte following membrane fusion as the factor responsible. This review summarises our current understanding of oocyte activation failure in human males, and describes recent advances in our knowledge linking certain cases of male infertility with defects in PLCζ expression and activity. Systematic literature searches were performed using PubMed and the ISI-Web of Knowledge. Databases compiled by the United Nations and World Health Organisation databases (UNWHO, and the Human Fertilization and Embryology Authority (HFEA were also scrutinised. It is clear that PLCζ plays a

Oocyte activation and phospholipase C zeta (PLCζ): diagnostic and therapeutic implications for assisted reproductive technology.

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Ramadan, Walaa M; Kashir, Junaid; Jones, Celine; Coward, Kevin

2012-07-09

Infertility affects one in seven couples globally and has recently been classified as a disease by the World Health Organisation (WHO). While in-vitro fertilisation (IVF) offers effective treatment for many infertile couples, cases exhibiting severe male infertility (19-57%) often remain difficult, if not impossible to treat. In such cases, intracytoplasmic sperm injection (ICSI), a technique in which a single sperm is microinjected into the oocyte, is implemented. However, 1-5% of ICSI cycles still fail to fertilise, affecting over 1000 couples per year in the UK alone. Pregnancy and delivery rates for IVF and ICSI rarely exceed 30% and 23% respectively. It is therefore imperative that Assisted Reproductive Technology (ART) protocols are constantly modified by associated research programmes, in order to provide patients with the best chances of conception. Prior to fertilisation, mature oocytes are arrested in the metaphase stage of the second meiotic division (MII), which must be alleviated to allow the cell cycle, and subsequent embryogenesis, to proceed. Alleviation occurs through a series of concurrent events, collectively termed 'oocyte activation'. In mammals, oocytes are activated by a series of intracellular calcium (Ca2+) oscillations following gamete fusion. Recent evidence implicates a sperm-specific phospholipase C, PLCzeta (PLCζ), introduced into the oocyte following membrane fusion as the factor responsible. This review summarises our current understanding of oocyte activation failure in human males, and describes recent advances in our knowledge linking certain cases of male infertility with defects in PLCζ expression and activity. Systematic literature searches were performed using PubMed and the ISI-Web of Knowledge. Databases compiled by the United Nations and World Health Organisation databases (UNWHO), and the Human Fertilization and Embryology Authority (HFEA) were also scrutinised. It is clear that PLCζ plays a fundamental role in the

Implication of fractionated dose exposures in therapeutic gain

International Nuclear Information System (INIS)

Kim, Hye-Jin; Lee, Min-Ho; Kim, Eun-Hee

2016-01-01

Radiation therapy pursues killing tumor cells while sparing normal cells from the radiation exposure. Stereotactic radiosurgery (SRS) is a cancer treatment modality that delivers a high dose in a single operation. This high-dose single operation shortens the treatment course, but can increase the risk of normal cell damage. Normal cell damage can be reduced by employing multi-directional exposures for an increasing number of isocenters. In this study, we investigated whether therapeutic benefits would be expected by employing new dose fractionation patterns at a high-dose single operation. The conventional single-dose operation in brain tumor radiosurgery is performed by delivering fractionated uniform doses. According to Figs. 2 and 3, the conventional radiosurgery might have obtained some therapeutic benefit by employing the fractionated uniform-dose exposures instead of a single-dose exposure. We suggest that further therapeutic gain be expected by employing the fractionated radiation exposures in an increasing dose pattern. Until ensuring our suggestion, the significance in gain of cell surviving should be verified for all three dose patterns with both normal and tumor cells. The investigation whether normal and tumor cells show the same responses to the fractionated dose exposures at lower and higher than 15 Gy of total dose is also reserved for future work

The therapeutic role of the dacryocystography in patients with epiphora: three cases report

International Nuclear Information System (INIS)

Francisco, Fabiano Celli; Carvalho, Antonio Carlos Pires; Torres Neto, Gilberto; Francisco, Marina Celli

2006-01-01

We describe three cases of patients that presented epiphora having been submitted the accomplishment of dacryocystographic study, which ones turned asymptomatic after the accomplishment of the exam, without any other procedure or medicine. The therapeutic potential of the method is stood out, once the literature on this subject is scarce in children and none in adults. (author)

Therapeutic monoclonal antibody N-glycosylation - Structure, function and therapeutic potential.

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Cymer, Florian; Beck, Hermann; Rohde, Adelheid; Reusch, Dietmar

2018-03-01

Therapeutic antibodies (IgG-type) contain several post-translational modifications (PTMs) whereby introducing a large heterogeneity, both structural and functional, into this class of therapeutics. Of these modifications, glycosylation in the fragment crystallizable (Fc) region is the most heterogeneous PTM, which can affect the stability of the molecule and interactions with Fc-receptors in vivo. Hence, the glycoform distribution can affect the mode of action and have implications for bioactivity, safety and efficacy of the drug. Main topics of the manuscript include: What factors influence the (Fc) glycan pattern in therapeutic antibodies and how can these glycans be characterized? How does structure of the Fc-glycan relate to function and what methods are available to characterize those functions? Although heterogeneous in their scope, the different sections are intended to combine current knowledge on structure-function correlations of IgG glycan structures with regard to Fc (effector) functions, as well as basic aspects and methodologies for their assessment. Copyright © 2017. Published by Elsevier Ltd.

Climate change and energy: The implications for the Spanish case

International Nuclear Information System (INIS)

Perez Arriaga, J. I.

2007-01-01

This paper examines the mutual implications between the climate change problem and the actual energy-at-a-crossroads situation of the unsustainable world energy model. The implications for the Spanish case are studied as a case example. The paper provides a brief review of the scientific evidence on climate change, analyzes the causes of the present energy dilemma and characterizes the problem to be addressed. The principal challenge for the future climate regime is to identify the nature and level of commitment that will provide sufficient incentives for all countries, with such a diversity of interests. The paper also exposes the most plausible framework for the future climate regime, the basic components of such a regime, the role to be played by the major stake holders and some guidelines for future negotiations. (Author)

Mechanisms and Therapeutic Implications of Cell Death Induction by Indole Compounds

International Nuclear Information System (INIS)

Ahmad, Aamir; Sakr, Wael A.; Rahman, KM Wahidur

2011-01-01

Indole compounds, obtained from cruciferous vegetables, are well-known for their anti-cancer properties. In particular, indole-3-carbinol (I3C) and its dimeric product, 3,3′-diindolylmethane (DIM), have been widely investigated for their effectiveness against a number of human cancers in vitro as well as in vivo. These compounds are effective inducers of apoptosis and the accumulating evidence documenting their ability to modulate multiple cellular signaling pathways is a testimony to their pleiotropic behavior. Here we attempt to update current understanding on the various mechanisms that are responsible for the apoptosis-inducing effects by these compounds. The significance of apoptosis-induction as a desirable attribute of anti-cancer agents such as indole compounds cannot be overstated. However, an equally intriguing property of these compounds is their ability to sensitize cancer cells to standard chemotherapeutic agents. Such chemosensitizing effects of indole compounds can potentially have major clinical implications because these non-toxic compounds can reduce the toxicity and drug-resistance associated with available chemotherapies. Combinational therapy is increasingly being realized to be better than single agent therapy and, through this review article, we aim to provide a rationale behind combination of natural compounds such as indoles with conventional therapeutics

The therapeutic implications of plasticity of the cancer stem cell phenotype.

Directory of Open Access Journals (Sweden)

Kevin Leder

2010-12-01

Full Text Available The cancer stem cell hypothesis suggests that tumors contain a small population of cancer cells that have the ability to undergo symmetric self-renewing cell division. In tumors that follow this model, cancer stem cells produce various kinds of specified precursors that divide a limited number of times before terminally differentiating or undergoing apoptosis. As cells within the tumor mature, they become progressively more restricted in the cell types to which they can give rise. However, in some tumor types, the presence of certain extra- or intracellular signals can induce committed cancer progenitors to revert to a multipotential cancer stem cell state. In this paper, we design a novel mathematical model to investigate the dynamics of tumor progression in such situations, and study the implications of a reversible cancer stem cell phenotype for therapeutic interventions. We find that higher levels of dedifferentiation substantially reduce the effectiveness of therapy directed at cancer stem cells by leading to higher rates of resistance. We conclude that plasticity of the cancer stem cell phenotype is an important determinant of the prognosis of tumors. This model represents the first mathematical investigation of this tumor trait and contributes to a quantitative understanding of cancer.

Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications.

Science.gov (United States)

Kraehenmann, Rainer

2017-01-01

A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or 'classical' psychedelics, such as the prototypical psychedelic drug lysergic acid diethylamide (LSD), psilocybin (4-phosphoryloxy-N,Ndimethyltryptamine), and ayahuasca - a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams, and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Research literature related to psychedelics and dreaming is reviewed, and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelicassisted therapy will be provided. Common features between psychedelic states and night dreams include perception, mental imagery, emotion activation, fear memory extinction, and sense of self and body. Differences between these two states are related to differential perceptual input from the environment, clarity of consciousness and meta-cognitive abilities. Therefore, psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness. The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine how therapeutic outcome is related to the acute dreamlike effects of psychedelics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications

Science.gov (United States)

Kraehenmann, Rainer

2017-01-01

Background: A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or ‘classical’ psychedelics such as the prototypical psychedelic drug lysergic acid diethylamide (LSD) psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and ayahuasca – a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Methods: Research literature related to psychedelics and dreaming is reviewed and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelic-assisted therapy will be provided. Results: Common features between psychedelic states and night dreams include perception mental imagery emotion activation fear memory extinction and sense of self and body. Differences between these two states are related to differential perceptual input from the environment clarity of consciousness and meta-cognitive abilities. Therefore psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness Conclusion: The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine how therapeutic outcome is related to the acute dreamlike effects of psychedelics. PMID:28625125

The special effects of hypnosis and hypnotherapy: A contribution to an ecological model of therapeutic change.

Science.gov (United States)

Mende, Matthias

2006-04-01

There is ample evidence that hypnosis enhances the effectiveness of psychotherapy and produces some astounding effects of its own. In this paper, the effective components and principles of hypnosis and hypnotherapy are analyzed. The "special" hypnotic and hypnotherapeutic effects are linked to the fact that the ecological requirements of therapeutic change are taken into account implicitly and/or explicitly when working with hypnotic trances in a therapeutic setting. The hypnotic situation is described--theoretically and in case examples--as a therapeutic modality that gratifies and aligns the basic emotional needs to feel autonomous, related, competent, and oriented. It is shown how the hypnotic relationship can help promote a sound ecological balance between these needs--a balance that is deemed to be a necessary prerequisite for salutogenesis. Practical implications for planning hypnotherapeutic interventions are discussed.

Obstetrical Antiphospholipid Syndrome: From the Pathogenesis to the Clinical and Therapeutic Implications

Science.gov (United States)

Marchetti, T.; Cohen, M.; de Moerloose, P.

2013-01-01

Antiphospholipid syndrome (APS) is an acquired thrombophilia with clinical manifestations associated with the presence of antiphospholipid antibodies (aPL) in patient plasma. Obstetrical APS is a complex entity that may affect both mother and fetus throughout the entire pregnancy with high morbidity. Clinical complications are as various as recurrent fetal losses, stillbirth, intrauterine growth restriction (IUGR), and preeclampsia. Pathogenesis of aPL targets trophoblastic cells directly, mainly via proapoptotic, proinflammatory mechanisms, and uncontrolled immunomodulatory responses. Actual first-line treatment is limited to low-dose aspirin (LDA) and low-molecular weight heparin (LMWH) and still failed in 30% of the cases. APS pregnancies should be a major field in obstetrical research, and new therapeutics are still in progress. PMID:23983765

Identifying Inconsistencies and Reporting Deficits in Therapeutic Massage and Bodywork (TMB) Case Reports Authored by TMB Practitioners: a TMB-Adapted CAse REport (CARE) Guidelines Audit Through 2014†

Science.gov (United States)

Munk, Niki; Shue, Sarah; Freeland, Emilee; Ralston, Rick; Boulanger, Karen T.

2016-01-01

Introduction Case reports are a fundamental tool through which therapeutic massage and bodywork (TMB) practitioners can inform research and impact their field by detailing the presentation, treatment, and follow-up of a single individual encountered in practice. Inconsistencies in case reporting limit their impact as fundamental sources of clinical evidence. Using the TMB-adapted CAse REport (CARE) guidelines, the current study sought to provide a rich description regarding the reporting quality of TMB practitioner authored TMB case reports in the literature. Methods 1) Systematic identification of published, peer-reviewed TMB case reports authored by TMB practitioners following PRISMA recommendations; 2) audit development based on TMB-adapted CARE guidelines; 3) audit implementation; and 4) descriptive analysis of audit scores. Results Our search identified 977 articles and 35 met study inclusion criteria. On average, TMB case reports included approximately 58% of the total items identified as necessary by the TMB-adapted CARE guidelines. Introduction sections of case reports had the best item reporting (80% on average), while Case Presentation (54%) and Results (52%) sections scored moderately overall, with only 20% of necessary Practitioner Description items included on average. Audit scores revealed inconsistent abstract reporting and few audited case reports including client race (20%), perspective (26%), and occupation/activities (40%); practitioner practice setting (12%), training (12%), scope-of-practice (29%), and credentialing (20%); adverse events or lack thereof (17%); and some aspect of informed consent (34%). Treatment descriptor item reporting varied from high to low. Various implications of concern are discussed. Conclusion The current audit and descriptive analysis highlight several reporting inconsistencies in TMB case reports prior to 2015. Reporting guidelines for case reports are important if standards for, and impact of, TMB case reports are

Obstetrical Antiphospholipid Syndrome: From the Pathogenesis to the Clinical and Therapeutic Implications

Directory of Open Access Journals (Sweden)

T. Marchetti

2013-01-01

Full Text Available Antiphospholipid syndrome (APS is an acquired thrombophilia with clinical manifestations associated with the presence of antiphospholipid antibodies (aPL in patient plasma. Obstetrical APS is a complex entity that may affect both mother and fetus throughout the entire pregnancy with high morbidity. Clinical complications are as various as recurrent fetal losses, stillbirth, intrauterine growth restriction (IUGR, and preeclampsia. Pathogenesis of aPL targets trophoblastic cells directly, mainly via proapoptotic, proinflammatory mechanisms, and uncontrolled immunomodulatory responses. Actual first-line treatment is limited to low-dose aspirin (LDA and low-molecular weight heparin (LMWH and still failed in 30% of the cases. APS pregnancies should be a major field in obstetrical research, and new therapeutics are still in progress.

The emerging pathogenic and therapeutic importance of the anaplastic lymphoma kinase gene.

LENUS (Irish Health Repository)

Kelleher, Fergal C

2012-02-01

The anaplastic lymphoma kinase gene (ALK) is a gene on chromosome 2p23 that has expression restricted to the brain, testis and small intestine but is not expressed in normal lymphoid tissue. It has similarity to the insulin receptor subfamily of kinases and is emerging as having increased pathologic and potential therapeutic importance in malignant disease. This gene was originally established as being implicated in the pathogenesis of rare diseases including inflammatory myofibroblastic tumour (IMT) and ALK-positive anaplastic large cell lymphoma, which is a subtype of non-Hodgkin\\'s lymphoma. Recently the number of diseases in which ALK is implicated in their pathogenesis has increased. In 2007, an inversion of chromosome 2 involving ALK and a fusion partner gene in a subset of non-small cell lung cancer was discovered. In 2008, publications emerged implicating ALK in familial and sporadic cases of neuroblastoma, a childhood cancer of the sympatho-adrenal system. Chromosomal abnormalities involving ALK are translocations, amplifications or mutations. Chromosomal translocations are the longest recognised ALK genetic abnormality. When translocations occur a fusion gene is created between ALK and a gene partner. This has been described in ALK-positive anaplastic large cell lymphoma in which ALK is fused to NPM (nucleolar protein gene) and in non-small cell lung cancer where ALK is fused to EML4 (Echinoderm microtubule-associated protein 4). The most frequently described partner genes in inflammatory myofibroblastic tumour are tropomyosin 3\\/4 (TMP3\\/4), however in IMTs a diversity of ALK fusion partners have been found, with the ability to homodimerise a common characteristic. Point mutations and amplification of the ALK gene occur in the childhood cancer neuroblastoma. Therapeutic targeting of ALK fusion genes using tyrosine kinase inhibition, vaccination using an ALK specific antigen and treatment using viral vectors for RNAi are emerging potential therapeutic

Pharmacological properties of angiotensin II antagonists: Examining all the therapeutic implications

Directory of Open Access Journals (Sweden)

Thomas Unger

2001-06-01

Full Text Available Angiotensin II (Ang II, the effector peptide of the renin-angiotensin system (RAS, exerts a variety of actions in physiological blood pressure and body fluid regulation, and is implicated as a major pathogenic factor in the development of cardiovascular disease. Inhibition of the RAS, via treatment with the angiotensin-converting enzyme inhibitors (ACE-I, or more recently the Ang II AT1-receptor blockers (ARBs, has been used as a therapeutic approach to the treatment of hypertension and other cardiovascular dysfunction. Evidence from animal and clinical studies shows that the antihypertensive and overall organ-protective actions of the ARBs are similar to those of ACE-I. However, as the ARBs selectively block the AT1-receptor, which is responsible for the known cardiovascular actions of Ang II, leave the AT2-receptor unopposed and do not interfere with the breakdown of bradykinin, there is the potential for beneficial effects in hypertensive patients with cardiovascular diseases such as left ventricular hypertrophy. Furthermore, there may be additional benefits when the ARBs are combined with ACE-I in such patients. Animal studies contribute to the elucidation and understanding of the role of AT1- and AT2-receptors in the cardiovascular system, and may help in the design of clinical studies aimed at investigating the effects of ACE-I, ARBs, and their combination, on cardiovascular outcomes in hypertensive patients.

Pharmacological properties of angiotensin II antagonists: examining all the therapeutic implications

Directory of Open Access Journals (Sweden)

Thomas Unger

2001-06-01

Full Text Available Angiotensin II (Ang II, the effector peptide of the renin-angiotensin system (RAS, exerts a variety of actions in physiological blood pressure and body fluid regulation, and is implicated as a major pathogenic factor in the development of cardiovascular disease. Inhibition of the RAS, via treatment with the angiotensin-converting enzyme inhibitors (ACE-I, or more recently the Ang II AT1-receptor blockers (ARBs, has been used as a therapeutic approach to the treatment of hypertension and other cardiovascular dysfunction. Evidence from animal and clinical studies shows that the antihypertensive and overall organ-protective actions of the ARBs are similar to those of ACE-I. However, as the ARBs selectively block the AT1-receptor, which is responsible for the known cardiovascular actions of Ang II, leave the AT2-receptor unopposed and do not interfere with the breakdown of bradykinin, there is the potential for beneficial effects in hypertensive patients with cardiovascular diseases such as left ventricular hypertrophy. Furthermore, there may be additional benefits when the ARBs are combined with ACE-I in such patients. Animal studies contribute to the elucidation and understanding of the role of AT1- and AT2-receptors in the cardiovascular system, and may help in the design of clinical studies aimed at investigating the effects of ACE-I, ARBs, and their combination, on cardiovascular outcomes in hypertensive patients.

Neurovascular cross talk in diabetic retinopathy: Pathophysiological roles and therapeutic implications

Science.gov (United States)

Moran, Elizabeth P.; Wang, Zhongxiao; Chen, Jing; Sapieha, Przemyslaw; Smith, Lois E. H.

2016-01-01

Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in developed countries, and its prevalence will increase as the global incidence of diabetes grows exponentially. DR begins with an early nonproliferative stage in which retinal blood vessels and neurons degenerate as a consequence of chronic hyperglycemia, resulting in vasoregression and persistent retinal ischemia, metabolic disequilibrium, and inflammation. This is conducive to overcompensatory pathological neovascularization associated with advanced proliferative DR. Although DR is considered a microvascular complication, the retinal microvasculature is intimately associated with and governed by neurons and glia; neurodegeneration, neuroinflammation, and dysregulation of neurovascular cross talk are responsible in part for vascular abnormalities in both early nonproliferative DR and advanced proliferative DR. Neuronal activity directly regulates microvascular dilation and blood flow in the process of neurovascular coupling. Retinal neurons also secrete guidance cues in response to injury, ischemia, or metabolic stress that may either promote or suppress vascular outgrowth, either alleviating or exacerbating DR, contingent on the stage of disease and retinal microenvironment. Neurodegeneration, impaired neurovascular coupling, and dysregulation of neuronal guidance cues are key events in the pathogenesis of DR, and correcting these events may prevent or delay development of advanced DR. The review discusses the mechanisms of neurovascular cross talk and its dysregulation in DR, and their potential therapeutic implications. PMID:27473938

Cellular retinoic acid bioavailability in various pathologies and its therapeutic implication.

Science.gov (United States)

Osanai, Makoto

2017-06-01

Retinoic acid (RA), an active metabolite of vitamin A, is a critical signaling molecule in various cell types. We found that RA depletion caused by expression of the RA-metabolizing enzyme CYP26A1 promotes carcinogenesis, implicating CYP26A1 as a candidate oncogene. Several studies of CYP26s have suggested that the biological effect of RA on target cells is primarily determined by "cellular RA bioavailability", which is defined as the RA level in an individual cell, rather than by the serum concentration of RA. Consistently, stellate cells store approximately 80% of vitamin A in the body, and the state of cellular RA bioavailability regulates their function. Based on the similarities between stellate cells and astrocytes, we demonstrated that retinal astrocytes regulate tight junction-based endothelial integrity in a paracrine manner. Since diabetic retinopathy is characterized by increased vascular permeability in its early pathogenesis, RA normalized retinal astrocytes that are compromised in diabetes, resulting in suppression of vascular leakiness. RA also attenuated the loss of the epithelial barrier in murine experimental colitis. The concept of "cellular RA bioavailability" in various diseases will be directed at understanding various pathologies caused by RA insufficiency, implying the potential feasibility of a therapeutic strategy targeting the stellate cell system. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Multiple roles and therapeutic implications of Akt signaling in cancer

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Emiliano Calvo

2009-06-01

Full Text Available Emiliano Calvo1, Victoria Bolós2, Enrique Grande21Centro Integral Oncológico Clara Campal (CiOCC, Madrid. Spain; 2Pfizer Oncology, Alcobendas-Madrid, SpainAbstract: The prominence of the PI3K-Akt signaling pathway in several tumors indicates a relationship with tumor grade and proliferation. Critical cellular processes are driven through this pathway. More detailed knowledge of the pathogenesis of tumors would enable us to design targeted drugs to block both membrane tyrosine kinase receptors and the intracellular kinases involved in the transmission of the signal. The newly approved molecular inhibitors sunitinib (an inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and other tyrosine kinase receptors, sorafenib (a serine–threonine kinase inhibitor that acts against B-Raf and temsirolimus (an mTOR inhibitor shown clinical activity in advanced kidney cancer. Chronic myeloid leukemia has changed its natural history thanks to imatinib and dasatinib, both of which inhibit the intracellular bcr/abl protein derived from the alteration in the Philadelphia chromosome. Intracellular pathways are still important in cancer development and their blockade directly affects outcome. Cross-talk has been observed but is not well understood. Vertical and horizontal pathway blockade are promising anticancer strategies. Indeed, preclinical and early clinical data suggest that combining superficial and intracellular blocking agents can synergize and leverage single-agent activity. The implication of the Akt signaling pathway in cancer is well established and has led to the development of new anticancer agents that block its activation.Keywords: Akt, cancer, therapeutic target, Akt inhibitors

Pancreas divisum: Analysis and therapeutic alternatives with a case report

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Jokić Radoica

2013-01-01

Full Text Available Introduction. Pancreas divisum is a relatively common pancreatic duct anatomic variant, firstly described in the 17th century. Case report. We reported a 2-year-old child admitted to the Pediatric Clinic with breathing difficulties and abdominal pains. Examination and X-ray image, showed a vast right hydrothorax containing rusty coloured solution with a high degree of amylase. Ultrasound and computed tomography examination revealed pancreatic polycyclic pseudocysts; following magnetic resonance cholangiopancreatography (MRCP, the diagnosis of pancreas divisum was confirmed. The general condition of the patient worsened, requiring an urgent operation. External drainage of the perforated pancreatic pseudocyst was performed. Following external fistula maturation, a change from external to internal drainage was performed using Roux-en-Y fistulojejunostomy. A 3-year postoperative period was uneventful. Conclusion. Pancreas divisum cases are unique requiring clinical experience, rational approach, and complex multimodal management. MRCP is a valuable diagnostic method. Amongst therapeutic options, outer and internal drainage can be seen as reliable methods. Further investigations are absolutely required to determine practical and appropriate conclusions.

Epidemiological, clinical, diagnostic and therapeutic survey in 505 cases with Brucellosis

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Haj Abdolbaghi M

2001-09-01

Full Text Available Brucellosis is an endemic disease in Iran with variety of clinical manifestation. Special characteristics of clinical diagnosis and treatment issues may cause some problems in manegement of patients. In this descriptive study 505 patients with Brucellosis retrospectively were evaluated from clinical point of view, Lab exams and therapeutic issues for 10 years (1990 to 1999. From 505 patients, 321 cases were male and 184 were female. 42.7 percent of cases were in age group of 10 to 30 years. Ingestion of un-pasteurized dairy products was detected in (66.7 percent and 31.86 percent of cases were sheep herders. The most common symptoms and signs were fever (65 percent, sweating (61 percent, arthritis (30.09 percent, sacroilitis (21.5 percent, orchitis (8.2 percent, spondylitis (2-3 percent and endocarditis (1.18. In this survery blood culture for Brucella melitensis became positive in 48.5 percent and bone marrow in 61 percent. Standard tube agglutination was positive in 96 percent (?1.80. Doxycyclin plus Rifampin was the most common regimen we used (37.8 percent. 4 patients died, but just one of those was directly because of Brucella Endocarditis. In this article we have discussed about some interesting cases as well.

The future orientation of constructive memory: an evolutionary perspective on therapeutic hypnosis and brief psychotherapy.

Science.gov (United States)

Rossi, Ernest; Erickson-Klein, Roxanna; Rossi, Kathryn

2008-04-01

We explore a new distinction between the future, prospective memory system being investigated in current neuroscience and the past, retrospective memory system, which was the original theoretical foundation of therapeutic hypnosis, classical psychoanalysis, and psychotherapy. We then generalize a current evolutionary theory of sleep and dreaming, which focuses on the future, prospective memory system, to conceptualize a new evolutionary perspective on therapeutic hypnosis and brief psychotherapy. The implication of current neuroscience research is that activity-dependent gene expression and brain plasticity are the psychobiological basis of adaptive behavior, consciousness, and creativity in everyday life as well as psychotherapy. We summarize a case illustrating how this evolutionary perspective can be used to quickly resolve problems with past obstructive procrastination in school to facilitate current and future academic success.

The therapeutic collaboration in life design counselling: The case of ...

African Journals Online (AJOL)

The collaboration coding system enables the assessment of each therapeutic exchange within and outside of the client's therapeutic zone of proximal development, defined as the space between the client's actual therapeutic developmental level and his/her potential developmental level fomented by a collaborative ...

Necroptosis: Modules and molecular switches with therapeutic implications.

Science.gov (United States)

Arora, Deepika; Sharma, Pradeep Kumar; Siddiqui, Mohammed Haris; Shukla, Yogeshwer

2017-06-01

Among the various programmed cell death (PCD) pathways, "Necroptosis" has gained much importance as a novel paradigm of cell death. This pathway has emerged as a backup mechanism when physiologically conserved PCD (apoptosis) is non-functional either genetically or pathogenically. The expanding spectrum of necroptosis from physiological development to diverse patho-physiological disorders, including xenobiotics-mediated toxicity has now grabbed the attention worldwide. The efficient role of necroptosis regulators in disease development and management are under constant examination. In fact, few regulators (e.g. MLKL) have already paved their way towards clinical trials and others are in queue. In this review, emphasis has been paid to the various contributing factors and molecular switches that can regulate necroptosis. Here we linked the overview of current knowledge of this enigmatic signaling with magnitude of therapeutics that may underpin the opportunities for novel therapeutic approaches to suppress the pathogenesis of necroptosis-driven disorders. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications

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Jordi Bover

2016-11-01

Full Text Available Cardiovascular (CV calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD–MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc., we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions.

Uterine arterial embolization for the treatment of adenomyosis: an analysis of therapeutic results in 80 cases

International Nuclear Information System (INIS)

Ai Zigang; Yang Yanfen; Guan Jie

2010-01-01

Objective: To discuss the therapeutic effect of uterine arterial embolization in treating adenomyosis. Methods: Uterine arterial embolization was performed in 80 patients with adenomyosis. The patients were followed up for 3, 6, 12 and 24 months after the operation. After the treatment the degree of dysmenorrhea, the menstrual flow and the uterine volume were observed and were compared with those before the treatment. Results: After uterine arterial embolization the clinical symptoms were relieved in all 80 patients. The menstrual flow was markedly decreased, the anemia was obviously improved and the uterine volume was significantly reduced, while the ovary functioning was not apparently affected. The symptom of dysmenorrhea completely disappeared one month after the therapy in 76 cases and four months after the therapy in the remaining 4 cases. Conclusion: Uterine arterial embolization is a mini-invasive and safe therapy with remarkable therapeutic results and few side-effects. Therefore, this treatment can significantly improve the patient's living quality. (authors)

K-12 Implications Seen in Some Cases before High Court

Science.gov (United States)

Walsh, Mark

2010-01-01

Arizona's variation on government vouchers for religious schools and California's prohibition on the sale of violent video games to minors present the top two cases with implications for education in the U.S. Supreme Court term that formally begins Oct. 4. New Justice Elena Kagan brings to the court extensive education policy experience as a…

Therapeutic platelet reduction: Use in postsplenectomy thrombocytosis

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Gita Negi

2015-01-01

Full Text Available Therapeutic platelet reduction is an effective modality for the reduction of platelet count in patients with treatment of extreme thrombocytosis resulting from a variety of primary and secondary causes of thrombocytosis, which may be associated with thrombotic or hemorrhagic complications of varying degrees. These cases when symptomatic fall into the ASFA Category II indication for therapeutic platelet apheresis procedure. Here, we report a case of postsplenectomy secondary thrombocytosis presenting with extremely high platelet counts and subsequent thrombosis in the shunt and successful treatment after therapeutic platelet reduction. The case is being presented to bring forth the fact that therapeutic platelet reduction is an easy procedure that gives quick and good results and also to bring to the attention of transfusion specialists an associated but as yet unreported procedural finding.

Evaluation of approved and non-approved requests for therapeutic abortion in cases referred to legal medicine organization of Lorestan province in 2013

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peyman Astaraki

2015-09-01

Full Text Available Background: Authorizing abortion in some cases of fetal and maternal diseases which was implemented by passing its law in 2005, a major change in therapeutic abortion was performed in Iran,s health system. Although there may be cases of illegal abortion, but our study examined legal abortion of Lorestan province in 2013, which led to increase in awareness of health professionals about indications of therapeutic abortion, the time to do it and answer to related questions. Materials and Methods: In this epidemiological and cross-sectional study, all applications for abortion permission, received by Lorestan legal organization in 2013, were studied. The data were recorded in a questionnaire and analyzed using SPSS software. Results: From 205 cases during a year, 144 of them obtained permission for abortion of which 88% issued for fetal abnormalities and 12% due to illness of the mother. The most common diseases in the fetus were, the brain and skull abnormalities, and in the mothers, cardiovascular diseases and hematologic abnormalities were the highest. In these cases, the most frequency belonged to the age group of 25-34 years. For 61 requests, permission for abortion had not been issued. High gestational age (26 cases and diseases of the brain and skull, were the most common reasons of request for abortion. Conclusion: Abortion means therapeutic abortion and with the increase in the authorized therapeutic abortion, the illegal abortion will be reduced and leads to increase in the health of pregnant women. By increasing awareness of the medical staff about permitted therapeutic abortion and related laws, a correct and better guidance of pregnant women, we can help them to have a healthy community. As well as the problems of obstetricians and gynecologists, in this field, will be decreased.

Therapeutic decisions in ALS patients: cross-cultural differences and clinical implications.

Science.gov (United States)

Andersen, Peter M; Kuzma-Kozakiewicz, Magdalena; Keller, Jürgen; Aho-Oezhan, Helena E A; Ciecwierska, Katarzyna; Szejko, Natalia; Vázquez, Cynthia; Böhm, Sarah; Badura-Lotter, Gisela; Meyer, Thomas; Petri, Susanne; Linse, Katharina; Hermann, Andreas; Semb, Olof; Stenberg, Erica; Nackberg, Simona; Dorst, Johannes; Uttner, Ingo; Häggström, Ann-Cristin; Ludolph, Albert C; Lulé, Dorothée

2018-05-04

Quantitative analysis of decision-making on therapeutic options in different sociocultural context in amyotrophic lateral sclerosis (ALS). ALS patients (n = 244) were consecutively recruited in Germany (n = 83), Poland (n = 83), and Sweden (n = 78) in a prospective cross-cultural study ( www.NEEDSinALS.com ). They were interviewed on preferences for therapeutic techniques including invasive (IV) and non-invasive ventilation (NIV), as well as percutaneous endoscopic gastrostomy (PEG) and on hypothetical termination of these using quantitative questions. Using standardized questionnaires, religiousness, personal values, quality of life, and depressiveness were assessed. NIV was most frequently used in Germany and PEG in Sweden. Swedish patients were most liberal on initiation and termination of PEG, NIV and IV. Polish patients were mostly undecided and were least likely to consider discontinuing supportive management. Current use was partly associated with age, gender and state of physical function; also, financial support explained some variance. Future preferences on therapeutic options from the patient's perspective were also closely associated with cultural factors. The more oriented towards traditional and conservative values, the less likely patients were to decide for invasive therapeutic devices (IV, PEG), the least likely to have ideations to discontinue any device and the more likely to have an undecided attitude. Current use of therapeutic options is determined by medical condition in analogy to clinical guidelines. For future considerations, other factors such as cultural background are crucial, yielding hurdles to be regarded in the implementation of advanced directives in a multicultural environment.

Therapeutic Dimensions of the Black Aesthetic

Science.gov (United States)

Toldson, Ivory L.; Pasteur, Alfred B.

1976-01-01

The authors of this article see the black aesthetic largely in terms of the affective component. Emotional oneness which is foreign to the white world view is the means by which the black man can achieve optimal mental health and development. The therapeutic implications of the black aesthetic are outlined. (NG)

The cephaloceles: A clinical, epidemiological and therapeutic study of 50 cases.

Science.gov (United States)

Kabré, A; Zabsonre, D S; Sanou, A; Bako, Y

2015-08-01

Cephaloceles are congenital malformations characterized by externalization of the meninges and/or brain tissue through a congenital skull bone defect. In developed countries, this malformation is rare but in our developing countries, this pathology remains one of our concerns. To describe the epidemiological, clinical and therapeutic aspects of the cephaloceles. A retrospective study was conducted from 2007 to 2013 on all cases of cephalocele supported in the department of neurosurgery of the Yalgado Ouédraogo University Teaching Hospital of Ouagadougou. The malformations were supplemented by CT scan. All patients were operated. The surgical procedure in cephaloceles of the convexity consisted of a direct approach. Sincipital cephaloceles were operated by transcranial approach or combined approach associating transcranial and transnasal approaches. Fifty patients were gathered during the 7-year period. There were 18 boys and 32 girls. The ages ranged from 1 day to 11 years. The cephaloceles were located on the vault of the skull in 78%; the lesion was sincipital in 22%. The malformation was covered with normal skin in 92%; it was pediculated in 78%. CT scan allowed the classification of cases as meningo-encephaloceles in 31 cases (62%) and meningoceles in 18 cases (36%) and one pure encephalocele. The immediate postoperative course was uneventful in 42 cases (84%); 8 postoperative deaths were recorded. At medium and long term, 4 patients (8%) developed complications of psychomotor deficiency in 3 cases and hydrocephalus in 1 case. The main reasons for the poor prognosis were superinfection, hydrocephalus and/or other brain malformations. Cephaloceles remain relatively frequent in our practice. After surgery, mental failure and hydrocephalus can occur impairing the prognosis. The most suitable solution is a policy of prevention with folic acid treatment before and during pregnancy and following up adequate pregnancies. Copyright © 2015 Elsevier Masson SAS. All

Cancer Stem Cells and Their Microenvironment: Biology and Therapeutic Implications

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Eunice Yuen-Ting Lau

2017-01-01

Full Text Available Tumor consists of heterogeneous cancer cells including cancer stem cells (CSCs that can terminally differentiate into tumor bulk. Normal stem cells in normal organs regulate self-renewal within a stem cell niche. Likewise, accumulating evidence has also suggested that CSCs are maintained extrinsically within the tumor microenvironment, which includes both cellular and physical factors. Here, we review the significance of stromal cells, immune cells, extracellular matrix, tumor stiffness, and hypoxia in regulation of CSC plasticity and therapeutic resistance. With a better understanding of how CSC interacts with its niche, we are able to identify potential therapeutic targets for the development of more effective treatments against cancer.

Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications.

Science.gov (United States)

Bover, Jordi; Ureña-Torres, Pablo; Górriz, José Luis; Lloret, María Jesús; da Silva, Iara; Ruiz-García, César; Chang, Pamela; Rodríguez, Mariano; Ballarín, José

Cardiovascular (CV) calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD) and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD-MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating) its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc.), we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Using therapeutic cloning to fight human disease: a conundrum or reality?

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Hall, Vanessa J; Stojkovic, Petra; Stojkovic, Miodrag

2006-07-01

The development and transplantation of autologous cells derived from nuclear transfer embryonic stem cell (NT-ESC) lines to treat patients suffering from disease has been termed therapeutic cloning. Human NT is still a developing field, with further research required to improve somatic cell NT and human embryonic stem cell differentiation to deliver safe and effective cell replacement therapies. Furthermore, the implications of transferring mitochondrial heteroplasmic cells, which may harbor aberrant epigenetic gene expression profiles, are of concern. The production of human NT-ESC lines also remains plagued by ethical dilemmas, societal concerns, and controversies. Recently, a number of alternate therapeutic strategies have been proposed to circumvent the moral implications surrounding human nuclear transfer. It will be critical to overcome these biological, legislative, and moral restraints to maximize the potential of this therapeutic strategy and to alleviate human disease.

Positive results of serological tests for syphilis in pregnancy – diagnostic and therapeutic problems, report of two cases

OpenAIRE

Marta Koper; Agnieszka B. Serwin; Anna Baran; Iwona Flisiak

2015-01-01

Introduction. Undiagnosed and untreated syphilis in pregnancy may result in subsequent complications: early fetal loss, stillbirth, low birth weight of infants and newborns with congenital syphilis. Objective. To analyze diagnostic and therapeutic dilemmas of positive results of serological tests for syphilis (STS) in pregnancy. Case reports. We present two cases of pregnant women, hospitalized in our department due to positive results of serological tests for syphilis, pe...

Therapeutic Assessment for Preadolescent Boys with Oppositional Defiant Disorder: A Replicated Single-Case Time-Series Design

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Smith, Justin D.; Handler, Leonard; Nash, Michael R.

2010-01-01

The Therapeutic Assessment (TA) model is a relatively new treatment approach that fuses assessment and psychotherapy. The study examines the efficacy of this model with preadolescent boys with oppositional defiant disorder and their families. A replicated single-case time-series design with daily measures is used to assess the effects of TA and to…

Tumor dedifferentiation: diagnostic and therapeutic implications

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Abhimanyu Jha

2017-09-01

Full Text Available Some of the neoplasm especially malignant tumors are notorious in masquerading their cell of origin because of additional mutations which drives them to differentiate into unusual phenotype. This is implicated to a phenomenon of tumor dedifferentiation which can mislead into inappropriate categorization and therapy. Dedifferentiation is well recognized in sarcomas such as liposarcoma, chondrosarcoma and MPNST. However, it can also develop in carcinomas, melanomas and lymphomas at initial diagnosis, following therapy or at recurrence.  The phenomenon has been reported in both primary tumors as well as at metastatic foci. A correct and early pathological identification of this phenomenon might profoundly help in guiding appropriate therapy. Clinical and radiological findings, immunohistochemistry and genetic analysis are often required for correct lineage identification of these tumors.

Universal design of workplaces through the use of Poka-Yokes: Case study and implications

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Cristóbal Miralles

2011-10-01

Full Text Available Purpose: Employment plays an important part in many people’s lives beyond merely providing income, since continued participation in work can have many therapeutic benefits for workers defined as disabled. However, disabled workers face a range of barriers to employment, despite legislation intended to improve workplace accessibility emphasizing adaptations to the workplace, which many employers often find difficult and expensive. The Poka-Yoke approach was developed in the manufacturing industry as a way of improving productivity by reducing errors using often very simple adaptations. This paper argues that, as Poka-Yokes are designed to make life easier and improve the performance of workers without impairments, they are closer to the philosophy of Universal Design than to Accessible Design, and offer an easy and inclusive way of making work more accessible for all kind of workers. Design/methodology/approach: This paper provides a case study demonstrating the use of the Poka-Yoke approach in a sheltered work centre for disabled; highlighting how they served to improve accessibility to work by fulfilling Universal Design principles. Findings: Our research allows us to demonstrate the great potential of Poka-yokes for gaining accessibility to the workplace. The real application of this approach, both in sheltered work centres and ordinary companies, can contribute to improve the high unemployment rates of disabled people. Research limitations/implications: The proposal is innovative and was applied in one specific company. Thus, a range of customized Poka-yokes would be desirable for different industrial sectors. Practical implications: Managers of sheltered work centres, and also of ordinary companies, can realize about the great potential of Poka-Yokes as an easy means of gaining flexibility and accessibility. Originality/value: There are very few papers relating lean manufacturing tools and disability. Our approach analyzes the benefits of

Clinical Implications of Measuring Drug and Anti-Drug Antibodies by Different Assays When Optimizing Infliximab Treatment Failure in Crohn's Disease

DEFF Research Database (Denmark)

Steenholdt, Casper; Bendtzen, Klaus; Brynskov, Jørn

2014-01-01

OBJECTIVES: Cost-effective guidance of therapeutic strategy in Crohn's disease patients with secondary infliximab (IFX) treatment failure may be achieved by serum IFX and anti-IFX antibody (Ab) measurements by radioimmunoassay (RIA). This study investigated implications of using other techniques...... on classification of underlying mechanism for treatment failure in most cases (79-94%). The majority (74-88%) failed IFX owing to pharmacodynamic problems, or had noninflammatory pathophysiology for symptoms resembling relapse. Applied threshold for therapeutic vs. subtherapeutic IFX level influenced...

Case Report: A Case of Severe Cerebral Malaria Managed with Therapeutic Hypothermia and Other Modalities for Brain Edema.

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Gad, AbdAllah; Ali, Sajjad; Zahoor, Talal; Azarov, Nick

2018-04-01

Malarial infections are uncommon in the United States and almost all reported cases stem from recent travelers coming from endemic countries. Cerebral malaria (CM) is a severe form of the disease usually affecting children and individuals with limited immunity. Despite proper management, mortality from CM can reach up to 25%, especially when it is associated with brain edema. Inefficient management of the edema may result in brain herniation and death. Uniform guidelines for management of CM-associated brain edema are lacking. In this report, we present a case of CM with associated severe brain edema that was successfully managed using a unique combination of therapeutic hypothermia, hypertonic saline, mannitol, and hyperventilation along with the antimalarial drugs quinidine and doxycycline. Our use of hypothermia was based on its proven benefit for improving neurological outcomes in post-cardiac arrest patients and previous in vitro research, suggesting its potential inhibitory role on malaria growth.

Evaluation of possible vertical fractures and therapeutic possibilities: A case report.

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Luis Espinoza

2012-12-01

Full Text Available Restorative treatment of endontic teeth supossed certain complications, especially when the restoration is not adequate. Indications for treatment vary according to the remaining tooth . In cases of which this one is moderated, it is chosen to rehabilitate by a type of indirect obturation, this can be in resin, ceramics or metal. A bad indication of restoration will lead to certain complications due to the fact that the rehabilitation of a treated tooth endodónticamente supposes in the majority of the cases an important challenge for the odontologist since it must solve the loss of structure dentaria, the minor resistance to the fracture before the forces oclusales and the need to provide sufficient retention to the material restorer who will replace the dental lost matter.Dental cracks corresponds to one of the recurring problems, the clinical diagnosis of accounting for it, usually cannot be verified radiographically and clinical examination is necessary.In some cases it opt prematurely for the exodoncy, the implications of this option for the stomatognathic balance should guide the clinician to ensure proper diagnosis and more conservative treatment plan, using the wide variety of new materials and adhesive systems, which allow patient's and clinician's satisfaction.We report the case of a patient presenting a dental crack in the tooth 2.4, which was treated conservatively, obtaining optimal results in terms of aesthetics and functionality.

Assessment of Bridelia ferruginea benth for its therapeutic potential ...

African Journals Online (AJOL)

McRoy

Therapeutic effect of Bridelia ferruginea on pregnancy-induced impaired glucose tolerance. Int J Med Biomed ... A proportion of women with pregnancy-induced impaired glucose ... The long-term implications for ... The leaves were removed ...

Two cases of acute leukemia developed after therapeutic radiation for malignant tumors

International Nuclear Information System (INIS)

Takahashi, Naoki; Matsuo, Kakaru; Yamaguchi, Hiroshi; Tsuno, Sumio; Toyoda, Shigeki

1978-01-01

Report was made as to two cases of acute leukemia developed after therapeutic radiation for malignant tumors. Both cases were exposed to atomic-bomb at the places 4 and 3 km far from the center of explosion, and they did not suffer from injuries and acute symptoms due to radiation. Case 1. -A 78 year old man had a mass in a right hypogastric region in April of 1975. In March of 1976, he received laparotomy and was diagnosed as malignant schwannoma. He received radiation therapy with 4,600 R and MFC therapy. In February of 1977, a clinical diagnosis of erythroleukemia was made according to the findings by bone marrow puncture, and he died in March. Postmortem examination revealed that main lesions were malignant schwannoma, its metastases, and leukemia. Case 2. -A 51 year old woman had a finger-tip sized tumor in the left breast in November of 1965, and had a radical operation on the basis of a diagnosis of comedo sarcoma. After that she received 60 Co irradiation with 18,800 R, and she was admitted in December of 1971, because she was suspected of having leukemia. She died in January of 1972. Postmortem examination revealed acute myelocytic leukemia. It is suspected that the onset of erythroleukemia within one year after irradiation would be influenced by MFC therapy in addition to radiotherapy. It was thought that leukemia in Case 2 was influenced by radiotherapy rather than atomic-bomb radioactivity. (Serizawa, K.)

Supernatural impotence: historical review with anthropological and clinical implications.

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Margolin, J; Witztum, E

1989-12-01

The historical and cultural background of the belief in supernatural impotence is presented, emphasizing its possible implications for clinical practice. A brief historical survey of the concept in Judaism and Christianity is followed by a short anthropological survey of supernatural impotence in different ethnic subcultures in Israel. A case demonstration exemplifies the connection between understanding the patient's cultural background and beliefs and the clinical competence of the therapist. The relationship between the clinical-therapeutic process in psychiatric practice and knowledge of the patient's cultural background and beliefs is stressed.

Anaesthesiological implications of Kimura's disease: a case report

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Sorbello Massimiliano

2009-06-01

Full Text Available Abstract Introduction Kimura's disease is a chronic inflammatory condition belonging to the angio-lymphatic proliferative group of disorders, usually affecting young men of Asian race, but is rare in Western countries. It is a benign but locally injurious disease, of unknown aetiology, whose classical clinical features are a tumour-like swelling, usually in the head and neck, with or without satellite lymphadenopathy, often accompanied by eosinophilia and elevated serum IgE. Case presentation We report the case of a 33-year-old Caucasian woman with an atypical localization of Kimura's disease, discussing the anaesthesiological implications and reviewing the current literature on Kimura's disease. Conclusions The diagnosis of Kimura's disease can be difficult and misleading, and anaesthesiological precautions could be ignored. Patients with this disease are often evaluated for other disorders: unnecessary diagnostic tests and investigations, or even surgery, may be avoided by just being aware of Kimura's disease.

Clinical neurorehabilitation - implications of the Reorganization of Elementary Functions (REF) model

DEFF Research Database (Denmark)

Rytter, Hana Malá; Mogensen, Jesper

The REF (Reorganization of Elementary Functions) model suggests mechanisms of posttraumatic reorganization, and resolves the contradiction between localization and functional recovery. In the process of developing this model, we have reconceptualised the term ‘function’ and introduced a concept...... across situations and cognitive domains. Since novel ASs are created and selected according to situation dependent feedback mechanisms, dissimilar external conditions may call for different ASs. Consequently, therapeutically established ASs may not be adequate in the settings of daily life. Additionally......, upon the loss of a particular brain structure, the structure and networks mediating recovery will not be identical in case of different cognitive and situational demands. Therapeutically, an important implication is that rehabilitative training should include as naturalistic settings as possible....

Therapeutic Hypothermia for Asphyxial Out-of-Hospital Cardiac Arrest Due to Drowning: A Systematic Review of Case Series and Case Reports.

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Suen, K-F; Leung, Reynold; Leung, Ling-Pong

2017-12-01

The objective of this review was to summarize published evidence of the effectiveness of therapeutic hypothermia in patients with drowning-associated asphyxial out-of-hospital cardiac arrest (OHCA) and to explore any preliminary favorable factors in the management of therapeutic hypothermia to improve survival and neurological outcome. Drowning may result in asphyxial OHCA or hypothermic OHCA, but the former does not provide any potential neuroprotective effect as the latter may do. Electronic literature searches of Ovid Medline, Embase, Cochrane Library, and Scopus were performed for all years from inception to July 2016. Primary studies in the form of case reports, letters to the editor, and others with higher quality are included, but guidelines, reviews, editorials, textbook chapters, conference abstracts, and nonhuman studies are excluded. Non-English articles are excluded. Relevant studies are then deemed eligible if the drowning OHCA patient's initial temperature was above 28°C, which implies asphyxial cardiac arrest, and intentional therapeutic hypothermia was instituted. Because of the narrow scope of interest and strict definition of the condition, limited studies addressed it, and no randomized controlled trials (RCT) could be selected. Thirteen studies covering 35 patients are included. No quantitative synthesis, assessment of study quality, or assessment of bias was performed. It is conjectured that extended therapeutic hypothermia of 48-72 hours might help prevent reperfusion injury during the intermediate phase of postcardiac arrest care to benefit patients of drowning-associated asphyxial OHCA, but this finding only serves as preliminary observation for future research. No conclusive recommendation could be made regarding the duration of and the time of onset of therapeutic hypothermia. Future research should put effort on RCT, particularly the effect of extended duration of 48-72 hours. Important parameters should be reported in detail. Asphyxial

Diagnostic and therapeutic value of laparoscopy for small bowel blunt injuries: A case report.

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Addeo, Pietro; Calabrese, Daniela Paola

2011-01-01

Small bowel injuries after blunt abdominal trauma represent both a diagnostic and a therapeutic challenge. Early diagnosis and prompt treatment are necessary in order to avoid a dangerous diagnostic delay. Laparoscopy can represent a diagnostic and therapeutic tool in patients with uncertain clinical symptoms. We report the case of a 25-year-old man, haemodynamically stable, admitted for acute abdominal pain a few hours after a physical assault. Giving the persistence of the abdominal pain and the presence of free fluids at the computed tomography examination, an exploratory laparoscopy was performed. At the laparoscopic exploration, an isolated small bowel perforation was found, 60 cm distal from the ligament of Treitz. The injury was repaired by laparoscopic suturing and the patient was discharged home at postoperative day 3 after an uneventful postoperative course. Laparoscopy represents a valuable tool for patients with small bowel blunt injuries allowing a timely diagnosis and a prompt treatment.

Multiple factor analysis of the therapeutic effect of 131I in treating 783 cases of Graves disease

International Nuclear Information System (INIS)

Cai Min; Li Xianfeng; Li Sijin; Chen Haibin

2008-01-01

Objective: To study the factors influencing therapeutic effect of 131 I in treating 783 cases of Graves disease. Methods: The values of various indexes were quantized on influencing factors such as age, sex, course of disease, mass of thyroid gland, the absorbed dose of 131 I per gram of thryoid gland, the given dose of 131 I, thyroid 24 h 131 I uptaking percentage, thyroid hormone and thyroid autoantibodys. The assessment of the therapeutic effect was made according to complete remission (including hypothyroidism) and partial remission after 131 I therapy. CMH χ 2 , Wilcoxon signed-rank test and Logistic regression were used to analyze the variable parameters before the treatment. Results: The therapeutic effect of 131 I is significant in the follow-up period (CMH χ 2 =69.21, P 131 I therapy for 12 months. The therapeutic effect was related to such factors as age thyroid mass, the absorbed dose of 131 I per gram of thryoid gland, thyroid 24 h 131 I uptaking percentage, etc (all the values of P 131 I uptaking percentage is higher, thyroid mass is bigger, thyroid gland is with noduses, the given dose of 131 I should be increased. Conversely decreased. (authors)

Conversational evidence in therapeutic dialogue.

Science.gov (United States)

Strong, Tom; Busch, Robbie; Couture, Shari

2008-07-01

Family therapists' participation in therapeutic dialogue with clients is typically informed by evidence of how such dialogue is developing. In this article, we propose that conversational evidence, the kind that can be empirically analyzed using discourse analyses, be considered a contribution to widening psychotherapy's evidence base. After some preliminaries about what we mean by conversational evidence, we provide a genealogy of evaluative practice in psychotherapy, and examine qualitative evaluation methods for their theoretical compatibilities with social constructionist approaches to family therapy. We then move on to examine the notion of accomplishment in therapeutic dialogue given how such accomplishments can be evaluated using conversation analysis. We conclude by considering a number of research and pedagogical implications we associate with conversational evidence.

8. Therapeutic and Educational Potential of Combining Cognitive Behavioural Therapy and Art – Qualitative Analysis of a Case Study

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Růžička Michal

2016-03-01

Full Text Available Cognitive behavioural psychotherapy is, just like other psychotherapeutic systems, of an eclectic nature. Should a therapist be successful across a wide range of issues, he/she needs to be adaptable, flexible and eclectic in terms of the techniques applied. Eclectically oriented therapists use a wide range of interventions; however, they adhere to individual theoretical structures. The aim of the paper is to point out the application of a combination of artistic activities within the system of the Cognitive behavioural therapy. For this purpose the paper presents a qualitative analysis of two case studies. We formulated the following research questions. Can the methods of combining the cognitive behavioural therapy and art accelerate the course of therapy? Can the methods of combining the cognitive behavioural therapy and art be perceived by the client as effective? The phenomenon investigated in the case study is a functional analysis of a client’s case and subsequent application of therapeutic and educational techniques of the Cognitive behavioural therapy and art. In both case studies it was demonstrated that the involvement of therapeutic elements accelerated the course of therapy. The clients in the research sample assessed the therapy as beneficial.

Clinical neurofeedback: case studies, proposed mechanism, and implications for pediatric neurology practice.

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Legarda, Stella B; McMahon, Doreen; Othmer, Siegfried; Othmer, Sue

2011-08-01

Trends in alternative medicine use by American health care consumers are rising substantially. Extensive literature exists reporting on the effectiveness of neurofeedback in the treatment of autism, closed head injury, insomnia, migraine, depression, attention deficit hyperactivity disorder, epilepsy, and posttraumatic stress disorder. We speculated that neurofeedback might serve as a therapeutic modality for patients with medically refractory neurological disorders and have begun referring patients to train with clinical neurofeedback practitioners. The modality is not always covered by insurance. Confident their child's medical and neurological needs would continue to be met, the parents of 3 children with epilepsy spectrum disorder decided to have their child train in the modality. The children's individual progress following neurofeedback are each presented here. A proposed mechanism and practice implications are discussed.

Melatonin-Based Therapeutics for Neuroprotection in Stroke

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Cesar V. Borlongan

2013-04-01

Full Text Available The present review paper supports the approach to deliver melatonin and to target melatonin receptors for neuroprotection in stroke. We discuss laboratory evidence demonstrating neuroprotective effects of exogenous melatonin treatment and transplantation of melatonin-secreting cells in stroke. In addition, we describe a novel mechanism of action underlying the therapeutic benefits of stem cell therapy in stroke, implicating the role of melatonin receptors. As we envision the clinical entry of melatonin-based therapeutics, we discuss translational experiments that warrant consideration to reveal an optimal melatonin treatment strategy that is safe and effective for human application.

Alexithymia in eating disorders: therapeutic implications

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Pinna F

2014-12-01

Full Text Available Federica Pinna, Lucia Sanna, Bernardo Carpiniello Department of Public Health, Clinical and Molecular Medicine - Unit of Psychiatry, University of Cagliari, Cagliari, Italy Abstract: A high percentage of individuals affected by eating disorders (ED achieve incomplete recovery following treatment. In an attempt to improve treatment outcome, it is crucial that predictors of outcome are identified, and personalized care approaches established in line with new treatment targets, thus facilitating patient access to evidence-based treatments. Among the psychological factors proposed as predictors of outcome in ED, alexithymia is of outstanding interest. The objective of this paper is to undertake a systematic review of the literature relating to alexithymia, specifically in terms of the implications for treatment of ED. In particular, issues concerning the role of alexithymia as a predictor of outcome and as a factor to be taken into account in the choice of treatment will be addressed. The effect of treatments on alexithymia will also be considered. A search of all relevant literature published in English using PubMed, PsycINFO, and Scopus databases was carried out on the basis of the following keywords: alexithymia, anorexia nervosa, bulimia nervosa, eating disorders, and treatment; no time limits were imposed. Despite the clinical relevance of alexithymia, the number of studies published on the above cited aspects is somewhat limited, and these studies are largely heterogeneous and feature significant methodological weaknesses. Overall, data currently available mostly correlate higher levels of alexithymia with a less favorable outcome in ED. Accordingly, alexithymia is seen as a relevant treatment target with the aim of achieving recovery of these patients. Treatments focusing on improving alexithymic traits, and specifically those targeting emotions, seem to show greater efficacy, although alexithymia levels often remain high even after specific

Importance of Therapeutic Drug Monitoring in the Treatment of Active Tuberculosis - A Retrospective Study of 4 Cases

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Sanaa HAMMI

2016-06-01

Full Text Available Background: In the treatment of active tuberculosis, therapeutic drug monitoring (TDM is used to optimize dosing that maximizes therapeutic benefit while minimizing toxicity. In Morocco, TDM is not routinely used, yet low levels of anti-TB drugs can be associated with poorer treatment outcomes.Methods: We retrospectively checked our archives for patients with active TB for whom TDM was performed during 2014. Medical records were reviewed to abstract demographic, clinical, radiographic and microbiological data including time until smear and culture conversion. Then, we looked for cases with delay of TB conversion.Results: In total, 24 patients were identified, for whom TDM was performed, they all had low serum drug levels. Among them, 4 patients showed delayed bacteriological conversion.Conclusions: Our study cases are showing the benefit of serum dosage in the follow-up of the patients showing a delay of sputum examination conversion, both direct and culture, during their evolutions. TDM is potentially useful for the treatment of active TB, but is currently underused in Morocco.

Cancer gene profiling in non-small cell lung cancers reveals activating mutations in JAK2 and JAK3 with therapeutic implications

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Shuyu D. Li

2017-10-01

Full Text Available Abstract Background Next-generation sequencing (NGS of cancer gene panels are widely applied to enable personalized cancer therapy and to identify novel oncogenic mutations. Methods We performed targeted NGS on 932 clinical cases of non-small-cell lung cancers (NSCLCs using the Ion AmpliSeq™ Cancer Hotspot panel v2 assay. Results Actionable mutations were identified in 65% of the cases with available targeted therapeutic options, including 26% of the patients with mutations in National Comprehensive Cancer Network (NCCN guideline genes. Most notably, we discovered JAK2 p.V617F somatic mutation, a hallmark of myeloproliferative neoplasms, in 1% (9/932 of the NSCLCs. Analysis of cancer cell line pharmacogenomic data showed that a high level of JAK2 expression in a panel of NSCLC cell lines is correlated with increased sensitivity to a selective JAK2 inhibitor. Further analysis of TCGA genomic data revealed JAK2 gain or loss due to genetic alterations in NSCLC clinical samples are associated with significantly elevated or reduced PD-L1 expression, suggesting that the activating JAK2 p.V617F mutation could confer sensitivity to both JAK inhibitors and anti-PD1 immunotherapy. We also detected JAK3 germline activating mutations in 6.7% (62/932 of the patients who may benefit from anti-PD1 treatment, in light of recent findings that JAK3 mutations upregulate PD-L1 expression. Conclusion Taken together, this study demonstrated the clinical utility of targeted NGS with a focused hotspot cancer gene panel in NSCLCs and identified activating mutations in JAK2 and JAK3 with clinical implications inferred through integrative analysis of cancer genetic, genomic, and pharmacogenomic data. The potential of JAK2 and JAK3 mutations as response markers for the targeted therapy against JAK kinases or anti-PD1 immunotherapy warrants further investigation.

Examining the therapeutic relationship and confronting resistances in psychodynamic psychotherapy: a certified public accountant case.

Science.gov (United States)

Manetta, Christopher T; Gentile, Julie P; Gillig, Paulette Marie

2011-05-01

Psychodynamic psychotherapy is effective for a variety of mental health symptoms. This form of psychotherapy uses patient self reflection and self examination, as well as the therapeutic relationship between the patient and psychiatrist, to explore maladaptive coping strategies and relationship patterns of the patient. A thorough understanding of resistance and the core conflictual relationship theme afford the psychiatrist the ability to facilitate this work. In this article, the composite case illustrates some of the psychodynamic psychotherapy techniques that can be employed in a psychotherapy case. In this example, the case is about a certified public accountant that came to treatment because of an acute stressor that put her career goals at risk. An acute episode or event can bring to light chronic and ongoing symptoms, which have had a remitting and relapsing course, and leave the patient unable to compensate on his or her own.

Visual and Motor Recovery After "Cognitive Therapeutic Exercises" in Cortical Blindness: A Case Study.

Science.gov (United States)

De Patre, Daniele; Van de Winckel, Ann; Panté, Franca; Rizzello, Carla; Zernitz, Marina; Mansour, Mariam; Zordan, Lara; Zeffiro, Thomas A; OʼConnor, Erin E; Bisson, Teresa; Lupi, Andrea; Perfetti, Carlo

2017-07-01

Spontaneous visual recovery is rare after cortical blindness. While visual rehabilitation may improve performance, no visual therapy has been widely adopted, as clinical outcomes are variable and rarely translate into improvements in activities of daily living (ADLs). We explored the potential value of a novel rehabilitation approach "cognitive therapeutic exercises" for cortical blindness. The subject of this case study was 48-year-old woman with cortical blindness and tetraplegia after cardiac arrest. Prior to the intervention, she was dependent in ADLs and poorly distinguished shapes and colors after 19 months of standard visual and motor rehabilitation. Computed tomographic images soon after symptom onset demonstrated acute infarcts in both occipital cortices. The subject underwent 8 months of intensive rehabilitation with "cognitive therapeutic exercises" consisting of discrimination exercises correlating sensory and visual information. Visual fields increased; object recognition improved; it became possible to watch television; voluntary arm movements improved in accuracy and smoothness; walking improved; and ADL independence and self-reliance increased. Subtraction of neuroimaging acquired before and after rehabilitation showed that focal glucose metabolism increases bilaterally in the occipital poles. This study demonstrates feasibility of "cognitive therapeutic exercises" in an individual with cortical blindness, who experienced impressive visual and sensorimotor recovery, with marked ADL improvement, more than 2 years after ischemic cortical damage.Video Abstract available for additional insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A173).

Yessotoxin, a Promising Therapeutic Tool

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Amparo Alfonso

2016-01-01

Full Text Available Yessotoxin (YTX is a polyether compound produced by dinoflagellates and accumulated in filter feeding shellfish. No records about human intoxications induced by this compound have been published, however it is considered a toxin. Modifications in second messenger levels, protein levels, immune cells, cytoskeleton or activation of different cellular death types have been published as consequence of YTX exposure. This review summarizes the main intracellular pathways modulated by YTX and their pharmacological and therapeutic implications.

Internet addiction neuroscientific approaches and therapeutical implications including smartphone addiction

CERN Document Server

Reuter, Martin

2017-01-01

The second edition of this successful book provides further and in-depth insight into theoretical models dealing with Internet addiction, as well as includes new therapeutical approaches. The editors also broach the emerging topic of smartphone addiction. This book combines a scholarly introduction with state-of-the-art research in the characterization of Internet addiction. It is intended for a broad audience including scientists, students and practitioners. The first part of the book contains an introduction to Internet addiction and their pathogenesis. The second part of the book is dedicated to an in-depth review of neuroscientific findings which cover studies using a variety of biological techniques including brain imaging and molecular genetics. The third part of the book focuses on therapeutic interventions for Internet addiction. The fourth part of the present book is an extension to the first edition and deals with a new emerging potential disorder related to Internet addiction – smartphone addicti...

Therapeutic indications and other use-case-driven updates in the drug ontology: anti-malarials, anti-hypertensives, opioid analgesics, and a large term request.

Science.gov (United States)

Hogan, William R; Hanna, Josh; Hicks, Amanda; Amirova, Samira; Bramblett, Baxter; Diller, Matthew; Enderez, Rodel; Modzelewski, Timothy; Vasconcelos, Mirela; Delcher, Chris

2017-03-03

The Drug Ontology (DrOn) is an OWL2-based representation of drug products and their ingredients, mechanisms of action, strengths, and dose forms. We originally created DrOn for use cases in comparative effectiveness research, primarily to identify historically complete sets of United States National Drug Codes (NDCs) that represent packaged drug products, by the ingredient(s), mechanism(s) of action, and so on contained in those products. Although we had designed DrOn from the outset to carefully distinguish those entities that have a therapeutic indication from those entities that have a molecular mechanism of action, we had not previously represented in DrOn any particular therapeutic indication. In this work, we add therapeutic indications for three research use cases: resistant hypertension, malaria, and opioid abuse research. We also added mechanisms of action for opioid analgesics and added 108 classes representing drug products in response to a large term request from the Program for Resistance, Immunology, Surveillance and Modeling of Malaria in Uganda (PRISM) project. The net result is a new version of DrOn, current to May 2016, that represents three major therapeutic classes of drugs and six new mechanisms of action. A therapeutic indication of a drug product is represented as a therapeutic function in DrOn. Adverse effects of drug products, as well as other therapeutic uses for which the drug product was not designed are dispositions. Our work provides a framework for representing additional therapeutic indications, adverse effects, and uses of drug products beyond their design. Our work also validated our past modeling decisions for specific types of mechanisms of action, namely effects mediated via receptor and/or enzyme binding. DrOn is available at: http://purl.obolibrary.org/obo/dron.owl . A smaller version without NDCs is available at: http://purl.obolibrary.org/obo/dron/dron-lite.owl.

Molecular Characterization of Gastric Carcinoma: Therapeutic Implications for Biomarkers and Targets

Directory of Open Access Journals (Sweden)

Lionel Kankeu Fonkoua

2018-03-01

Full Text Available Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC. Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2 amplification and programmed death-ligand 1 (PD-L1 expression for effectiveness of trastuzumab and pembrolizumab, respectively. Multi-platform molecular analysis of cancer, including GC, may help identify predictive biomarkers to guide selection of therapeutic agents. Molecular classification of GC by The Cancer Genome Atlas Research Network and the Asian Cancer Research Group is expected to identify therapeutic targets and predictive biomarkers. Complementary to molecular characterization of GC is molecular profiling by expression analysis and genomic sequencing of tumor DNA. Initial analysis of patients with gastroesophageal carcinoma demonstrates that the ratio of progression-free survival (PFS on molecular profile (MP-based treatment to PFS on treatment prior to molecular profiling exceeds 1.3, suggesting the potential value of MP in guiding selection of individualized therapy. Future strategies aiming to integrate molecular classification and profiling of tumors with therapeutic agents for achieving the goal of personalized treatment of GC are indicated.

Molecular Characterization of Gastric Carcinoma: Therapeutic Implications for Biomarkers and Targets.

Science.gov (United States)

Kankeu Fonkoua, Lionel; Yee, Nelson S

2018-03-09

Palliative chemotherapy is the mainstay of treatment of advanced gastric carcinoma (GC). Monoclonal antibodies including trastuzumab, ramucirumab, and pembrolizumab have been shown to provide additional benefits. However, the clinical outcomes are often unpredictable and they can vary widely among patients. Currently, no biomarker is available for predicting treatment response in the individual patient except human epidermal growth factor receptor 2 (HER2) amplification and programmed death-ligand 1 (PD-L1) expression for effectiveness of trastuzumab and pembrolizumab, respectively. Multi-platform molecular analysis of cancer, including GC, may help identify predictive biomarkers to guide selection of therapeutic agents. Molecular classification of GC by The Cancer Genome Atlas Research Network and the Asian Cancer Research Group is expected to identify therapeutic targets and predictive biomarkers. Complementary to molecular characterization of GC is molecular profiling by expression analysis and genomic sequencing of tumor DNA. Initial analysis of patients with gastroesophageal carcinoma demonstrates that the ratio of progression-free survival (PFS) on molecular profile (MP)-based treatment to PFS on treatment prior to molecular profiling exceeds 1.3, suggesting the potential value of MP in guiding selection of individualized therapy. Future strategies aiming to integrate molecular classification and profiling of tumors with therapeutic agents for achieving the goal of personalized treatment of GC are indicated.

Clinical study of fetal liver transplantation in treatment of four cases of accidental or therapeutic acute radiation sickness

International Nuclear Information System (INIS)

1989-01-01

This report summarized the clinical experience of fetal liver transplantation (FLT) in the medical handling of accidental (case 1) or therapeutic (cases 2-4) acute radiation sickness of severe haemopoietic form. In addition to receiving 80 mg/kg of cyclophosphamide, cases 2, 3 and 4 were exposed to total body single irradiation of 5.5, 5.0 and 5.0 Gy, respectively; while case 1 was exposed to whole body irradiation of 5.2 Gy only. The total number of nucleated fetal liver cells transplanted was 2.26-4.1 x 10 8 /kg. Only 2-5% of peripheral blood cells of cases 2, 3 and 4 were found to have allogeneic marker. The author points out that FLT may be beneficial in those cases of accidental irradiation or patients with acute leukemia when there were no HLA-identical bone marrow donors available

Glioblastoma Stem-Like Cells—Biology and Therapeutic Implications

International Nuclear Information System (INIS)

Gürsel, Demirkan B.; Shin, Benjamin J.; Burkhardt, Jan-Karl; Kesavabhotla, Kartik; Schlaff, Cody D.; Boockvar, John A.

2011-01-01

The cancer stem-cell hypothesis proposes that malignant tumors are likely to encompass a cellular hierarchy that parallels normal tissue and may be responsible for the maintenance and recurrence of glioblastoma multiforme (GBM) in patients. The purpose of this manuscript is to review methods for optimizing the derivation and culturing of stem-like cells also known as tumor stem cells (TSCs) from patient-derived GBM tissue samples. The hallmarks of TSCs are that they must be able to self-renew and retain tumorigenicity. The isolation, optimization and derivation of TSCs as outlined in this review, will be important in understanding biology and therapeutic applications related to these cells

Therapeutic plasma exchange: an effective treatment in ethylene dibromide poisoning cases.

Science.gov (United States)

Pahwa, Naresh; Bharani, Rajesh; Jain, Manish; Argal, Suarabh; Soni, Harish; Kosta, Susmit; Kumar, Ravindra

2013-10-01

Ethylene dibromide (EDB) poisoning is very common in Central India and has fatal outcome. EDB is highly protein bound and, therefore, it is suggested that therapeutic plasma exchange (TPE) may be useful in removing drug from body shortly after ingestion before EDB metabolizes and causes severe end organ damage. The aim of our study is to find the effect of time of start of TPE on survival outcome of EDB poisoning cases. Fifty-eight cases of EDB poisoning were reviewed from 2007 to 2012 in Department of critical care medicine in tertiary care hospitals at Indore. Five patients were discharged against medical advice and lost to follow up. TPE was done in 47 patients as early as possible and irrespective of appearance of clinical symptoms. TPE was not performed in six cases as they were hypotensive at admission. The patients with EDB poisoning were 15-45 yrs old with 3:2 male to female ratio. Out of 47 who received TPE, 39 patients survived. TPE had started within 24 h of ingestions of EDB in 36 out of 39 survived patients. Survival outcome was nine times higher in patients who received TPE within 24 h than after 24 h of ingestion. Survival rate was increased to 100% in patients where TPE was done within 12 h of ingestion of EDB. Early TPE help to remove plasma protein bound toxin with significant mortality reduction. However, delay in start of TPE after ingestion of poison has significant poor survival outcome. Copyright © 2013 Wiley Periodicals, Inc.

Personal identity narratives of therapeutic songwriting participants following Spinal Cord Injury: A case series analysis.

Science.gov (United States)

Roddy, Chantal; Rickard, Nikki; Tamplin, Jeanette; Baker, Felicity Anne

2018-07-01

Spinal Cord Injury (SCI) patients face unique identity challenges associated with physical limitations, higher comorbid depression, increased suicidality and reduced subjective well-being. Post-injury identity is often unaddressed in subacute rehabilitation environments where critical physical and functional rehabilitation goals are prioritized. Therapeutic songwriting has demonstrated prior efficacy in promoting healthy adjustment and as a means of expression for post-injury narratives. The current study sought to examine the identity narratives of therapeutic songwriting participants. Case-series analysis of the individual identity trajectories of eight individuals. Subacute rehabilitation facility, Victoria, Australia. Eight individuals with an SCI; 7 males and 1 female. Six-week therapeutic songwriting intervention facilitated by a music therapist to promote identity rehabilitation. Identity, subjective well-being and distress, emotional state. Three participants demonstrated positive trajectories and a further three showed negative trajectories; remaining participants were ambiguous in their response. Injury severity differentiated those with positive trajectories from those with negative trajectories, with greater injury severity apparent for those showing negative trends. Self-concept also improved more in those with positive trajectories. Core demographic variables did not however meaningfully predict the direction of change in core identity or wellbeing indices. Identity-focused songwriting holds promise as a means of promoting healthy identity reintegration. Further research on benefits for those with less severe spinal injuries is warranted.

The Slaying of a Beautiful Hypothesis: The Efficacy of Counseling and the Therapeutic Process

Science.gov (United States)

Hauser, Mike; Hays, Danica G.

2010-01-01

Although the efficacy of counseling has been empirically linked to the therapeutic process, the emphasis in much of the literature remains on technique use. This article discusses 3 components of therapeutic efficacy (i.e., common factors, working alliance, and counselor attributes) and provides implications for counselors and counselor training.…

[Are therapeutics decisions homogeneous in multidisciplinary onco-urology staff meeting? Comparison of therapeutic options taken in four departments from Paris].

Science.gov (United States)

Audenet, F; Lejay, V; Mejean, A; De La Taille, A; Abbou, C-C; Lebret, T; Botto, H; Bitker, M-O; Roupret, M

2012-06-01

One of the priorities of the "Plan against the Cancer" in France is to ensure the discussion of all cancer cases in a multidisciplinary meeting staff (RCP). The multidisciplinary collaboration is proposed to guarantee a discussion between specialists in every cases, particularly in complex cases. The aim of this study was to compare the therapeutic decision taken in four RCP in Paris Île-de-France academic centres for three identical cases. Three cases of urological oncology (prostate cancer [PCa], renal cell carcinoma [RCC] and bladder tumour) were selected by a single urologist, not involved in further discussion. These cases were blindly presented in four academic urology department from Paris: Pitié-Salpêtrière Hospital, Mondor Hospital, the Georges-Pompidou European Hospital and Foch Hospital. The four centres met the criteria of quality of RCP in terms of multidisciplinarity, frequency and standardization. The therapeutic suggestions were similar in the RCC cases, there were differences in the surgical approaches and preoperative work-up in the PCa case and, lastly, the proposals were different for the bladder cancer case. The decisions relies on clinical data and preoperative work-up but also on the experience and habits of the centre of excellence. For complex cases that does not fit with current guidelines, the panel discussion can lead to different therapeutic options from a centre to another and is largely influenced by the local organisation of the RCP. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Supporting Affect Regulation in Children With Multiple Disabilities During Psychotherapy: A Multiple Case Design Study of Therapeutic Attachment. [Miscellaneous Article

NARCIS (Netherlands)

Schuengel, C; Sterkenburg, P S; Jeczynski, P; Janssen, C G C; Jongbloed, G

2009-01-01

: In a controlled multiple case design study, the development of a therapeutic relationship and its role in affect regulation were studied in 6 children with visual disabilities, severe intellectual disabilities, severe challenging behavior, and prolonged social deprivation. In the 1st phase,

Understanding Music's Therapeutic Efficacy with Implications for Why Music Matters

Science.gov (United States)

Thram, Diane

2015-01-01

In this essay, I focus on how attention to music's therapeutic efficacy is important to the praxial music education philosophy espoused by Elliott and Silverman. I note, despite the use of the term praxis from Aristotle's philosophy dating back to antiquity, there is no mention in Music Matters 2 of what historical evidence tells us about how…

Therapeutic Endoscopy for the Control of Nonvariceal Upper Gastrointestinal Bleeding in Children: A Case Series.

Science.gov (United States)

Banc-Husu, Anna M; Ahmad, Nuzhat A; Chandrasekhara, Vinay; Ginsberg, Gregory G; Jaffe, David L; Kochman, Michael L; Rajala, Michael W; Mamula, Petar

2017-04-01

Gastrointestinal bleeding is one of the most common indications for urgent endoscopy in the pediatric setting. The majority of these procedures are performed for control of variceal bleeding, with few performed for nonvariceal upper gastrointestinal (NVUGI) bleeding. The data on therapeutic endoscopy for NVUGI are sparse. The aims of our study were to review our experience with NVUGI bleeding, describe technical aspects and outcomes of therapeutic endoscopy, and determine gastroenterology fellows' training opportunities according to the national training guidelines. We performed a retrospective review of endoscopy database (Endoworks, Olympus Inc, Center Valley, PA) from January 2009 to December 2014. The search used the following keywords: bleeding, hematemesis, melena, injection, epinephrine, cautery, clip, and argon plasma coagulation. The collected data included demographics, description of bleeding lesion and medical/endoscopic therapy, rate of rebleeding, relevant laboratories, physical examination, and need for transfusion and surgery. The study was approved by the institutional review board. During the study period 12,737 upper endoscopies (esophagogastroduodenoscopies) were performed. A total of 15 patients underwent 17 esophagogastroduodenoscopies that required therapeutic intervention to control bleeding (1:750 procedures). The mean ± standard deviation (median) age of patients who required endoscopic intervention was 11.6 ± 6.0 years (14.0 years). Seven out of 17 patients received dual therapy to control the bleeding lesions. All but 3 patients received medical therapy with intravenous proton pump inhibitor, and 3 received octreotide infusions. Six of the patients experienced rebleeding (40%), with 4 out of 6 initially only receiving single modality therapy. Two of these patients eventually required surgical intervention to control bleeding and both patients presented with bleeding duodenal ulcers. There were no cases of aspiration

An improved interim therapeutic restoration technique for management of anterior early childhood caries: report of two cases.

Science.gov (United States)

Nelson, Travis

2013-01-01

Early childhood caries presents unique treatment challenges that often require advanced behavior management techniques, such as general anesthesia or procedural sedation. In some cases, use of these pharmacologic adjuncts is undesirable or not possible. The interim therapeutic restoration is a treatment method that, while sometimes employed in such cases, can often produce unsatisfactory results in primary anterior teeth. This is often due to insufficient bulk of material and lack of retention. The purpose of this report was to describe a simple alternative technique (resin modified glass ionomer strip crowns) that may be employed to deliver esthetic anterior restorations to marginally cooperative children in the dental clinic setting and to report on two cases in which it was successfully used. \\\\\\Department of Pediatric Dentistry, University of Washington, Seattle, Wash., USA. tmnelson@uw.edu

Therapeutic implications of manipulating and mining the microbiota.

LENUS (Irish Health Repository)

Shanahan, Fergus

2009-09-01

The gut microbiota is increasingly recognized as a health asset but occasionally is a contributor to the pathogenesis of both gastrointestinal and certain extra-intestinal disorders. This is driving research interest, the pace of which has been greatly facilitated by new molecular technologies for studying mixed microbial populations, including the non-cultivable sector. In addition, it appears that elements of a modern lifestyle such as diet, domestic hygiene, urbanization, antibiotic usage and family size, may represent proxy markers of environmental influence on the composition of the microbiota colonizing the host in early life. While manipulation of the microbiota has become a therapeutic strategy in certain clinical disorders, the prospect of mining host-microbe-dietary interactions for novel drug discovery may become an even more intriguing reality.

Small molecule modulators of epigenetic modifications: implications in therapeutics

International Nuclear Information System (INIS)

Ruthrotha Selvi, B.; Senapati, Parijat; Kundu, Tapas K.

2012-01-01

The eukaryotic genome is organized into chromatin, a nucleoprotein complex and a dynamic entity that regulates the spatio-temporal expression of genes in response to the intracellular and extracellular signals. This dynamicity is maintained by several factors, including the chromatin modifying Machineries. Chromatin modifying enzymes (for example, lysine (K) acetyl transferases for acetylation, lysine and arginine (R) methyltransferases for methylation, etc.) by virtue of their modifying abilities of both histones and the non histone components, are vital regulatory factors for gene expression both in physiological as well as pathophysiological conditions. Hence the modulators (inhibitors/activators) of these enzymes, which are capable of altering the gene expression globally, could also be useful in understanding the epigenetic mechanism of gene expression as well as for therapeutic purposes. We have found that acetylation of histone chaperone NPM1 and histones is essential for chromatin-mediated transcriptional activation. Remarkably, NPM1 as well as histones get hyperacetylated predominantly in oral cancer patient samples. We identified NPM1 as a positive regulator of the KAT, p300 autoacetylation, the possible causal mechanism of hyperacetylation. Targeting the acetylation by a water-soluble KAT inhibitor, CTK7A in oral tumour xenografted mice, we could demonstrate that the tumour growth could indeed be retarded upon the inhibition of KAT autoacetylation. Presently, we are studying the histone modification language in oral cancer, especially in the context of acetylation and methylation which could be potential targets for combinatorial epigenetic therapeutics. (author)

Exosomes as a tumor immune escape mechanism: possible therapeutic implications

Directory of Open Access Journals (Sweden)

Hanley Harold H

2008-07-01

Full Text Available Abstract Advances in cancer therapy have been substantial in terms of molecular understanding of disease mechanisms, however these advances have not translated into increased survival in the majority of cancer types. One unsolved problem in current cancer therapeutics is the substantial immune suppression seen in patients. Conventionally, investigations in this area have focused on antigen-nonspecific immune suppressive molecules such as cytokines and T cell apoptosis inducing molecules such as Fas ligand. More recently, studies have demonstrated nanovesicle particles termed exosomes are involved not only in stimulation but also inhibition of immunity in physiological conditions. Interestingly, exosomes secreted by cancer cells have been demonstrated to express tumor antigens, as well as immune suppressive molecules such as PD-1L and FasL. Concentrations of exosomes from plasma of cancer patients have been associated with spontaneous T cell apoptosis, which is associated in some situations with shortened survival. In this paper we place the "exosome-immune suppression" concept in perspective of other tumor immune evasion mechanisms. We conclude by discussing a novel therapeutic approach to cancer immune suppression by extracorporeal removal of exosomes using hollow fiber filtration technology

Immunogenomic Classification of Colorectal Cancer and Therapeutic Implications

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Jessica Roelands

2017-10-01

Full Text Available The immune system has a substantial effect on colorectal cancer (CRC progression. Additionally, the response to immunotherapeutics and conventional treatment options (e.g., chemotherapy, radiotherapy and targeted therapies is influenced by the immune system. The molecular characterization of colorectal cancer (CRC has led to the identification of favorable and unfavorable immunological attributes linked to clinical outcome. With the definition of consensus molecular subtypes (CMSs based on transcriptomic profiles, multiple characteristics have been proposed to be responsible for the development of the tumor immune microenvironment and corresponding mechanisms of immune escape. In this review, a detailed description of proposed immune phenotypes as well as their interaction with different therapeutic modalities will be provided. Finally, possible strategies to shift the CRC immune phenotype towards a reactive, anti-tumor orientation are proposed per CMS.

miRNAs in inflammatory skin diseases and their clinical implications

DEFF Research Database (Denmark)

Løvendorf, Marianne B; Skov, Lone

2015-01-01

biological processes. The clinical implications of miRNAs are intriguing, both from a diagnostic and a therapeutic perspective. Accordingly, there is emerging evidence for the clinical potential of miRNAs as both biomarkers and possible therapeutic targets in skin diseases. Future studies will hopefully...... incomplete; however, it is known that miRNAs are implicated in various cellular processes of both normal and diseased skin. Some miRNAs appear to be consistently deregulated in several different inflammatory skin diseases, including psoriasis and atopic dermatitis, indicating a common role in fundamental...

ErbB polymorphisms: Insights and implications for response to targeted cancer therapeutics

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Moulay A Alaoui-Jamali

2015-02-01

Full Text Available Advances in high-throughput genomic-scanning have expanded the repertory of genetic variations in DNA sequences encoding ErbB tyrosine kinase receptors in humans, including single nucleotide polymorphisms (SNPs, polymorphic repetitive elements, microsatellite variations, small-scale insertions and deletions. The ErbB family members: EGFR, ErbB2, ErbB3 and ErbB4 receptors are established as drivers of many aspects of tumor initiation and progression to metastasis. This knowledge has provided rationales for the development of an arsenal of anti-ErbB therapeutics, ranging from small molecule kinase inhibitors to monoclonal antibodies. Anti-ErbB agents are becoming the cornerstone therapeutics for the management of cancers that overexpress hyperactive variants of ErbB receptors, in particular ErbB2-positive breast cancer and non-small cell lung carcinomas. However, their clinical benefit has been limited to a subset of patients due to a wide heterogeneity in drug response despite the expression of the ErbB targets, attributed to intrinsic (primary and to acquired (secondary resistance. Somatic mutations in ErbB tyrosine kinase domains have been extensively investigated in preclinical and clinical setting as determinants for either high sensitivity or resistance to anti-ErbB therapeutics. In contrast, only scant information is available on the impact of SNPs, which are widespread in genes encoding ErbB receptors, on receptor structure and activity, and their predictive values for drug susceptibility. This review aims to briefly update polymorphic variations in genes encoding ErbB receptors based on recent advances in deep sequencing technologies, and to address challenging issues for a better understanding of the functional impact of single versus combined SNPs in ErbB genes to receptor topology, receptor-drug interaction, and drug susceptibility. The potential of exploiting SNPs in the era of stratified targeted therapeutics is discussed.

Real time CT-fluoroscopy: diagnostic and therapeutic applications

International Nuclear Information System (INIS)

Mey, J. de; Op de Beeck, B.; Meysman, M.; Noppen, M.; Maeseneer, M. de; Vanhoey, M.; Vincken, W.; Osteaux, M.

2000-01-01

The synergetic progression of CT technology and computer hardware has made ultrafast acquisition and image reconstruction possible. This has lead to the availability of CT interactive diagnosis and therapeutic procedures. Making use of our own material (337 intervention procedures during the last 17 months), we have compared our techniques and results to the recent literature data. One of the advantages of the biopsy technique is an improved sensitivity for neoplastic lesions, most certainly in cases of intrapulmonary lesions, surrounded by aerated tissue (now 94% compared to 87% in our previous study). A second advantage is the safety of the technique (only one major complication in our series). Fluid collection drainages, and more complex interventions like local injection of drugs, radio-frequency ablation, wire hook placement and ethanol injection were performed without complication. Yet another interesting feature is the shortening of the procedure time (reduced in average to an 'in-room' time of less than 30 min), which has definite economical implications. Furthermore it increases the patient's comfort and safety, and extends the scope of outpatient procedures (80% outpatient procedures in our material). On the other side the radiation exposure can be raised as an issue, especially when we consider the operator's hands. However, the described technique and the use of dedicated tools can alleviate the problem. As a conclusion, real time CT fluoroscopy has given a new input and broadens the scope of clinical indications of CT-guided diagnostic and therapeutic procedures

Therapeutical attitudes in tooth supported overdentures with ball attachements. Case report.

Science.gov (United States)

Țâncu, A M; Melescanu Imre, M; Preoteasa, C T; Preoteasa, E

2014-01-01

Tooth supported overdenture with ball attachments has a number of advantages in prosthetics, but presents some difficulties as well, which sometimes make impossible the use of these anchoring systems; these difficulties should be well known. In this regard we present a suggestive case. It is the case of a patient, aged 57, who came for treatment, suffering from subtotal maxillary and mandibular edentulism (present 11 and 21, respectively 33 and 43), previously having an overdenture prosthesis on natural teeth, with special systems - ball attachment type, dissatisfied with the treatment (due to repeated fractures and functional intolerance to dentures). Clinical examination revealed an increase of the vertical dimension of occlusion and reduced prosthetic space at a correct, functional DVO value, aspects that were explaining the patient's reported complaints. As a therapeutic approach, having into consideration the balance conditions that were favorable for complete dentures and the large ball attachments volume, which did not allow keeping them at a functional DVO at any of the jaws, and the relatively young age of the patient, it was decided to remove the ball attachments and to keep the teeth for a simple overdenture, both to the maxillar and the mandible, over coronary reduced teeth, enough to allow the denture thickness at a functional DVO. Good end result of prosthetics, with stable, functional dentures, which were well tolerated and offered satisfaction to the patient, have led to an increased quality of life.

Therapeutical attitudes in tooth supported overdentures with ball attachements. Case report

Science.gov (United States)

Țâncu, AM; Melescanu Imre, M; Preoteasa, CT; Preoteasa, E

2014-01-01

Tooth supported overdenture with ball attachments has a number of advantages in prosthetics, but presents some difficulties as well, which sometimes make impossible the use of these anchoring systems; these difficulties should be well known. In this regard we present a suggestive case. It is the case of a patient, aged 57, who came for treatment, suffering from subtotal maxillary and mandibular edentulism (present 11 and 21, respectively 33 and 43), previously having an overdenture prosthesis on natural teeth, with special systems – ball attachment type, dissatisfied with the treatment (due to repeated fractures and functional intolerance to dentures). Clinical examination revealed an increase of the vertical dimension of occlusion and reduced prosthetic space at a correct, functional DVO value, aspects that were explaining the patient’s reported complaints. As a therapeutic approach, having into consideration the balance conditions that were favorable for complete dentures and the large ball attachments volume, which did not allow keeping them at a functional DVO at any of the jaws, and the relatively young age of the patient, it was decided to remove the ball attachments and to keep the teeth for a simple overdenture, both to the maxillar and the mandible, over coronary reduced teeth, enough to allow the denture thickness at a functional DVO. Good end result of prosthetics, with stable, functional dentures, which were well tolerated and offered satisfaction to the patient, have led to an increased quality of life. PMID:27057258

An integrative view of mechanisms underlying generalized spike-and-wave epileptic seizures and its implication on optimal therapeutic treatments.

Directory of Open Access Journals (Sweden)

Boyuan Yan

Full Text Available Many types of epileptic seizures are characterized by generalized spike-and-wave discharges. In the past, notable effort has been devoted to understanding seizure dynamics and various hypotheses have been proposed to explain the underlying mechanisms. In this paper, by taking an integrative view of the underlying mechanisms, we demonstrate that epileptic seizures can be generated by many different combinations of synaptic strengths and intrinsic membrane properties. This integrative view has important medical implications: the specific state of a patient characterized by a set of biophysical characteristics ultimately determines the optimal therapeutic treatment. Through the same view, we further demonstrate the potentiation effect of rational polypharmacy in the treatment of epilepsy and provide a new angle to resolve the debate on polypharmacy. Our results underscore the need for personalized medicine and demonstrate that computer modeling and simulation may play an important role in assisting the clinicians in selecting the optimal treatment on an individual basis.

Clinical, diagnostic and therapeutic management of patients with breast tuberculosis: Analysis of 46 Cases

Directory of Open Access Journals (Sweden)

Murat Ozgur Kilic

2016-01-01

Full Text Available Breast tuberculosis is a rare form of extrapulmonary tubercular infection. Our aim is to highlight the nonspecific clinical presentations, diagnostic difficulties and therapeutic approaches of mammarian tuberculosis. Forty-six patients diagnosed with breast tuberculosis between 2005 and 2015 were reviewed retrospectively. Clinical features, all diagnostic methods, and the outcomes of treatment were analysed. All cases were female with a mean age of 36.4 years. Breast mass and pain were the most common complaints. While 34.8% of the cases had a physical examination with suspicions for malignancy, 43.5% of the patients had Breast Imaging Reporting and Data System (BI-RADS 4 or 5 lesions suggested malignancy radiologically. Definitive diagnosis was based on histopathologic examination through core needle biopsy (n = 29, excisional biopsy (n = 12, and open biopsy (n = 5 taken from the abscess wall during drainage. Standard antiTB therapy for 6 months was given to all cases. Thirty-three patients recovered with standard 6-month therapy while extended treatment for 9–12 months was needed in 13 (28.2% cases. Surgery was carried out in 17 cases. Two patients developed recurrence. Breast tuberculosis can be easily confused with breast cancer, suppurative abscess, and other causes of granulomatous mastitis, both clinically and radiologically. A multidisciplinary approach is required to prevent diagnostic delays and unnecessary surgical interventions. Although antiTB therapy is the mainstay treatment of breast TB, surgery is usually indicated in patients refractory to medical treatment.

Bioenergy and its implication for yoga therapy

Directory of Open Access Journals (Sweden)

Chathapuram Rajan Narayanan

2018-01-01

Full Text Available Electro photonic imaging (EPI is being researched relative to its application for yoga therapy. Three parameters of interest in EPI measurements are as follows: Communication energy (C, integral or normalized area (IA, and Entropy (E. It is important to note that C indicates the total energy of communication for the organ system; IA is an indication of total amount of energy that is available for the organ system while entropy is an indication of the amount of coherence of the energy. Coherence and entropy are inversely related; this means less the entropy, more the coherence and vice versa. Illustrative cases of successful therapy with yoga practices in a wide variety of abnormal conditions are examined, and in every case, entropy is shown to decrease for the affected organ system while communication energy stays within stable range. Relative to the electromagnetic (Rubik and living matrix (Oschman models, it is suggested that the regulation of energy, its coherence in the biological system and interaction with life processes provide the basis for model building and design of health-promoting procedures. Further, this approach is examined relative to yoga theory, traditional medicine systems, and scientific developments in the field of gene expression and neuroplasticity and a generalized model that we call Unified System of Medicine is proposed. This model has direct implications on methods used to control the environmental factors to get robust results from EPI application for therapeutic purposes. Implications for furthering research in yoga therapy using EPI and implications of EPI as a translational technology between traditional medicine systems and modern medicine is discussed.

[Diabetic retinopathy: pathogenesis and therapeutic implications].

Science.gov (United States)

Pelikánová, Terezie

Diabetic retinopathy (DR) develops in patients with both type 1 and type 2 diabetes and is the major cause of vision loss and blindness in the working population. The main risk factor of DR is hyperglycemia accompanied by enhanced mitochondrial production of reactive oxygen species and oxidative stress, formation of advanced glycation end products (AGE) and hexosamines, increase in polyol metabolism of glucose. The severity of vascular injury depends on the individual genetic background and is modified by other epigenetic, metabolic and haemodynamic factors, including hypertension, dyslipidemia and oxidative stress. In diabetes, damage to the retina occurs in the vasculature (endothelial cells and pericytes), neurons and glia, pigment epithelial cells and infiltrating immunocompetent cells: monocytes, granulocytes, lymfocytes. These activated cells change the production pattern of a number of mediators such as growth factors, proinflammatory cytokines, vasoactive molecules, coagulation factors and adhesion molecules resulting in increased blood flow, increased capillary permeability, proliferation of extracellular matrix and thickening of basal membranes, altered cell turnover (apoptosis, proliferation, hypertrophy), procoagulant and proaggregant pattern, and finally in angiogenesis and tissue remodelling. Brain, liver, adipose tissue, GUT, skeletal muscle and other tissues could be another source of mediators. Therapeutic approaches used for patients with or at risk for diabetic retinopathy include drug therapy to reduce modifiable risk factors, laser photocoagulation, intravitreous administration of anti-VEGF agents/steroids and intraocular surgery. Screening plays an important role in early detection and intervention to prevent the progression of diabetic retinopathy. Described insights into pathophysiological mechanisms responsible for DR, could help in the development of more targeted approach for prevention and treatment of diabetic retinopathy. anti

Psychomotor Retardation in Depression: A Systematic Review of Diagnostic, Pathophysiologic, and Therapeutic Implications

Directory of Open Access Journals (Sweden)

Djamila Bennabi

2013-01-01

Full Text Available Psychomotor retardation is a central feature of depression which includes motor and cognitive impairments. Effective management may be useful to improve the classification of depressive subtypes and treatment selection, as well as prediction of outcome in patients with depression. The aim of this paper was to review the current status of knowledge regarding psychomotor retardation in depression, in order to clarify its role in the diagnostic management of mood disorders. Retardation modifies all the actions of the individual, including motility, mental activity, and speech. Objective assessments can highlight the diagnostic importance of psychomotor retardation, especially in melancholic and bipolar depression. Psychomotor retardation is also related to depression severity and therapeutic change and could be considered a good criterion for the prediction of therapeutic effect. The neurobiological process underlying the inhibition of activity includes functional deficits in the prefrontal cortex and abnormalities in dopamine neurotransmission. Future investigations of psychomotor retardation should help improve the understanding of the pathophysiological mechanisms underlying mood disorders and contribute to improving their therapeutic management.

Granulomatous orchitis. A report of three new cases

International Nuclear Information System (INIS)

Inchusta, M.I.; Mellado, M.T.; Pina, L.; Caballero, P.

1997-01-01

Granulomatous orchitis (GO) is an unusual testicular process. The significance of the diagnosis of this type of testicular disease takes root in the therapeutic implications that derive from it, since on many occasions it is impossible to differentiate from testicular cancer. The purpose of this study is to communicate the ultrasound features of three patients presenting with GO, that differ in some aspects from the ones described up to now, such as the little or the absence of hydroceles and the presence in one case, of extra testicular calcification. (Author) 4 refs

Nanotechnology and regenerative therapeutics in plastic surgery: The next frontier

Science.gov (United States)

Tan, Aaron; Chawla, Reema; Natasha, G; Mahdibeiraghdar, Sara; Jeyaraj, Rebecca; Rajadas, Jayakumar; Hamblin, Michael R.; Seifalian, Alexander M.

2015-01-01

Summary The rapid ascent of nanotechnology and regenerative therapeutics as applied to medicine and surgery has seen an exponential rise in the scale of research generated in this field. This is evidenced not only by the sheer volume of papers dedicated to nanotechnology but also in a large number of new journals dedicated to nanotechnology and regenerative therapeutics specifically to medicine and surgery. Aspects of nanotechnology that have already brought benefits to these areas include advanced drug delivery platforms, molecular imaging and materials engineering for surgical implants. Particular areas of interest include nerve regeneration, burns and wound care, artificial skin with nanoelectronic sensors and head and neck surgery. This study presents a review of nanotechnology and regenerative therapeutics, with focus on its applications and implications in plastic surgery. PMID:26422652

Ovarian steroids, stem cells and uterine leiomyoma: therapeutic implications.

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Moravek, Molly B; Yin, Ping; Ono, Masanori; Coon, John S; Dyson, Matthew T; Navarro, Antonia; Marsh, Erica E; Chakravarti, Debabrata; Kim, J Julie; Wei, Jian-Jun; Bulun, Serdar E

2015-01-01

Uterine leiomyoma is the most common benign tumor in women and is thought to arise from the clonal expansion of a single myometrial smooth muscle cell transformed by a cellular insult. Leiomyomas cause a variety of symptoms, including abnormal uterine bleeding, pelvic pain, bladder or bowel dysfunction, and recurrent pregnancy loss, and are the most common indication for hysterectomy in the USA. A slow rate of cell proliferation, combined with the production of copious amounts of extracellular matrix, accounts for tumor expansion. A common salient feature of leiomyomas is their responsiveness to steroid hormones, thus providing an opportunity for intervention. A comprehensive search of PUBMED was conducted to identify peer-reviewed literature published since 1980 pertinent to the roles of steroid hormones and somatic stem cells in leiomyoma, including literature on therapeutics that target steroid hormone action in leiomyoma. Reviewed articles were restricted to English language only. Studies in both animals and humans were reviewed for the manuscript. Estrogen stimulates the growth of leiomyomas, which are exposed to this hormone not only through ovarian steroidogenesis, but also through local conversion of androgens by aromatase within the tumors themselves. The primary action of estrogen, together with its receptor estrogen receptor α (ERα), is likely mediated via induction of progesterone receptor (PR) expression, thereby allowing leiomyoma responsiveness to progesterone. Progesterone has been shown to stimulate the growth of leiomyoma through a set of key genes that regulate both apoptosis and proliferation. Given these findings, aromatase inhibitors and antiprogestins have been developed for the treatment of leiomyoma, but neither treatment results in complete regression of leiomyoma, and tumors recur after treatment is stopped. Recently, distinct cell populations were discovered in leiomyomas; a small population showed stem-progenitor cell properties, and

Breast cancer lung metastasis: Molecular biology and therapeutic implications.

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Jin, Liting; Han, Bingchen; Siegel, Emily; Cui, Yukun; Giuliano, Armando; Cui, Xiaojiang

2018-03-26

Distant metastasis accounts for the vast majority of deaths in patients with cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving bone, liver, lung, and brain. Breast cancer can be divided into different subtypes based on gene expression profiles, and different breast cancer subtypes show preference to distinct organ sites of metastasis. Luminal breast tumors tend to metastasize to bone while basal-like breast cancer (BLBC) displays a lung tropism of metastasis. However, the mechanisms underlying this organ-specific pattern of metastasis still remain to be elucidated. In this review, we will summarize the recent advances regarding the molecular signaling pathways as well as the therapeutic strategies for treating breast cancer lung metastasis.

Mentoring Postsecondary Tenure-Track Faculty: A Theory-Building Case Study and Implications for Institutional Policy

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Davis, Dannielle Joy; Boyer, Patricia; Russell, Isela

2011-01-01

The featured research uses theory-building case study to understand the experiences of junior faculty in a mentoring program. Findings suggest the importance of professional interaction for faculty members' integration into their campus communities. An explanatory model illustrates the findings and supplements discussion of the implications for…

[Therapeutic response to plasmapheresis in four cases with obsessive-compulsive disorder and tic disorder triggered by streptococcal infections].

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Beşiroğlu, Lütfullah; Ağargün, Mehmet Yücel; Ozbebit, Ozgür; Sözen, Mehmet; Dilek, Imdat; Güleç, Mustafa

2007-01-01

The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been assigned to a subgroup of patients experiencing pediatric onset obsessive-compulsive symptoms and tics as a result of autoimmune response to group A beta-hemolytic streptococcal infection. It has been hypothesized that an immune process initiated by infection affects the basal ganglia and causes neuropsychiatric symptoms. In cases with severe neuropsychiatric symptoms, the use of treatment strategies that interrupt the autoimmune process responsible for the pathogenesis of PANDAS, such as therapeutic plasmapheresis or intravenous immunoglobulin, has been proposed. In this paper, we discuss the effect of plasmapheresis treatment in 4 adult cases of obsessive-compulsive disorder and tic disorder triggered by streptococcal infections.

Worsening cholestasis and possible cefuroxime-induced liver injury following "successful" therapeutic endoscopic retrograde cholangiopancreatography for a distal common bile duct stone: a case report.

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Niriella, Madunil Anuk; Kumarasena, Ravindu Sujeewa; Dassanayake, Anuradha Supun; Pathirana, Aloka; de Silva Hewavisenthi, Janaki; de Silva, Hithanadura Janaka

2016-12-21

Cefuroxime very rarely causes drug-induced liver injury. We present a case of a patient with paradoxical worsening of jaundice caused by cefuroxime-induced cholestasis following therapeutic endoscopic retrograde cholangiopancreatography for a distal common bile duct stone. A 51-year-old, previously healthy Sri Lankan man presented to our hospital with obstructive jaundice caused by a distal common bile duct stone. Endoscopic retrograde cholangiopancreatography with stone extraction, common bile duct clearance, and stenting failed to improve the cholestasis, with paradoxical worsening of his jaundice. A liver biopsy revealed features of drug-induced intrahepatic cholestasis. Although his case was complicated by an episode of cholangitis, the patient made a complete recovery in 4 months with supportive treatment and withdrawal of the offending drug. This case highlights a very rare drug-induced liver injury caused by cefuroxime as well as our approach to treating a patient with paradoxical worsening of jaundice after therapeutic endoscopic retrograde cholangiopancreatography.

Molecular alterations in acute myeloid leukemia and their clinical and therapeutical implications.

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Infante, María Stefania; Piris, Miguel Ángel; Hernández-Rivas, José Ángel

2018-06-09

Acute myeloid leukaemia is the most common form of acute leukaemia, and its incidence increases with age. The disease derives from a transformed multipotent malignant haematopoietic stem cell that acquires consequent genomic alterations. The identification of recurrent cytogenetic anomalies associated with different patterns of acute myeloid leukaemia clinical presentation has led to the incorporation of genetic markers in clinical decision-making. In addition, the observation that these anomalies may mark therapeutic responses and relapse and survival rates have been incorporated into the World Health Organisation's recent molecular classification and stratification and the European Leukaemia Net, with the aim of creating prognostic categories that help rationalise better diagnosis, prognosis, re-evaluation of the disease and the combination of therapeutic protocols in order to increase the survival rate of these patients. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Cancer stem cells in hepatocellular carcinoma: Therapeutic implications based on stem cell biology.

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Chiba, Tetsuhiro; Iwama, Atsushi; Yokosuka, Osamu

2016-01-01

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer-related death worldwide. Despite advances in its diagnosis and treatment, the prognosis of patients with advanced HCC remains unfavorable. Recent advances in stem cell biology and associated technologies have enabled the identification of minor components of tumorigenic cells, termed cancer stem cells (CSC) or tumor-initiating cells, in cancers such as HCC. Furthermore, because CSC play a central role in tumor development, metastasis and recurrence, they are considered to be a therapeutic target in cancer treatment. Hepatic CSC have been successfully identified using functional and cell surface markers. The analysis of purified hepatic CSC has revealed the molecular machinery and signaling pathways involved in their maintenance. In addition, epigenetic transcriptional regulation has been shown to be important in the development and maintenance of CSC. Although inhibitors of CSC show promise as CSC-targeting drugs, novel therapeutic approaches for the eradication of CSC are yet to be established. In this review, we describe recent progress in hepatic CSC research and provide a perspective on the available therapeutic approaches based on stem cell biology. © 2015 The Japan Society of Hepatology.

Clinical picture and treatment implication in a child with Capgras syndrome: a case report

OpenAIRE

Mazzone, Luigi; Armando, Marco; De Crescenzo, Franco; Demaria, Francesco; Valeri, Giovanni; Vicari, Stefano

2012-01-01

Abstract Introduction Capgras syndrome is a delusional misidentification syndrome characterized by the patient’s belief that his or her relatives have been replaced by impostors. Case presentation Here we describe the clinical picture and the therapeutic approach to an 11-year-old Caucasian girl with Capgras syndrome. A complete psychopathological assessment was conducted during the acute phase, at one month, two months and six months since diagnosis. Conclusion Subsequent follow-up evaluatio...

Cancer Stem Cells and Molecular Biology Test in Colorectal Cancer: Therapeutic Implications.

Science.gov (United States)

Effendi-Ys, Rustam

2017-10-01

Colorectal cancer (CRC) is the third most frequent cancer in males, the second in females, and is the second leading cause of cancer related death worldwide. Within Indonesia's 250 million population, the incidence rates for CRC per 100,000 population were 15.2 for males and 10.2 for females, and estimated 63,500 cases per year.  More than 50% of colorectal cancer patients will develop metastasis. CRC is still the main cause of tumor-related death, and although most CRC patients are treated with surgery to remove the tumor tissue, some of the CRC patients recurred. Chemotherapy used as adjuvant or neoadjuvant therapy also has several problems, in which these treatments are useless in tumor cells with chemo-resistance. Molecular testing of CRC from tumor tissues has important implications for the selection of treatment. Biomarkers can be used as prognostic value, molecular predictive factors, and targeted therapy. Recent research reported that, cancer stem cells (CSCs) are considered as the origin of tumorigenesis, development, metastasis and recurrence. At present, it has been shown that CSCs existed in many tumors including CRC. This review aims to summarize the issue on CSCs, and the future development of drugs that target colorectal cancer stem cells.

Written case formulations in the treatment of anorexia nervosa: Evidence for therapeutic benefits.

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Allen, Karina L; O'Hara, Caitlin B; Bartholdy, Savani; Renwick, Beth; Keyes, Alexandra; Lose, Anna; Kenyon, Martha; DeJong, Hannah; Broadbent, Hannah; Loomes, Rachel; McClelland, Jessica; Serpell, Lucy; Richards, Lorna; Johnson-Sabine, Eric; Boughton, Nicky; Whitehead, Linette; Treasure, Janet; Wade, Tracey; Schmidt, Ulrike

2016-09-01

Case formulation is a core component of many psychotherapies and formulation letters may provide an opportunity to enhance the therapeutic alliance and improve treatment outcomes. This study aimed to determine if formulation letters predict treatment satisfaction, session attendance, and symptom reductions in anorexia nervosa (AN). It was hypothesized that higher quality formulation letters would predict greater treatment satisfaction, a greater number of attended sessions, and greater improvement in eating disorder symptoms. Patients were adult outpatients with AN (n = 46) who received Maudsley Anorexia Nervosa Treatment for Adults (MANTRA) in the context of a clinical trial. A Case Formulation Rating Scheme was used to rate letters for adherence to the MANTRA model and use of a collaborative, reflective, affirming stance. Analyses included linear regression and mixed models. Formulation letters that paid attention to the development of the AN predicted greater treatment acceptability ratings (p = 0.002). More reflective and respectful letters predicted greater reductions in Eating Disorder Examination scores (p = 0.003). Results highlight the potential significance of a particular style of written formulation as part of treatment for AN. Future research should examine applicability to other psychiatric disorders. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:874-882). © 2016 Wiley Periodicals, Inc.

Stem cell terminology: practical, theological and ethical implications.

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Shanner, Laura

2002-01-01

Stem cell policy discussions frequently confuse embryonic and fetal sources of stem cells, and label untested, non-reproductive cloning as "therapeutic." Such misnomers distract attention from significant practical and ethical implications: accelerated research agendas tend to be supported at the expense of physical risks to women, theological implications in a multi-faith community, informed consent for participation in research, and treatment decisions altered by unrealistic expectations.

Ethical Implications of Case-Based Payment in China: A Systematic Analysis.

Science.gov (United States)

Jin, Pingyue; Biller-Andorno, Nikola; Wild, Verina

2015-12-01

How health care providers are paid affects how medicine is practiced. It is thus important to assess provider payment models not only from the economic perspective but also from the ethical perspective. China recently started to reform the provider payment model in the health care system from fee-for-service to case-based payment. This paper aims to examine this transition from an ethical perspective. We collected empirical studies on the impact of case-based payment in the Chinese health care system and applied a systematic ethical matrix that integrates clinical ethics and public health ethics to analyze the empirical findings. We identified eleven prominent ethical issues related to case-based payment. Some ethical problems of case-based payment in China are comparable to ethical problems of managed care and diagnosis related groups in high-income countries. However, in this paper we discuss in greater detail four specific ethical issues in the Chinese context: professionalism, the patient-physician relationship, access to care and patient autonomy. Based on the analysis, we cautiously infer that case-based payment is currently more ethically acceptable than fee-for-service in the context of China, mainly because it seems to lower financial barriers to access care. Nonetheless, it will be difficult to justify the implementation of case-based payment if no additional measures are taken to monitor and minimize its existing negative ethical implications. © 2014 John Wiley & Sons Ltd.

Therapeutic outcome of various treatment modalities for the management of 34 cases of mandibular unicystic ameloblastoma

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Rajib Khadka

2018-03-01

Full Text Available Background & Objectives: Unicystic ameloblastoma is a challenge, as conservative modalities have high recurrence chances whereas radical modalities have high morbidity for defects and deformity. Enucleation with peripheral ostectomy and Carnoy’s solution is an intermediate treatment with less risk of recurrence and good outcome. The objectives of the study was to determine the therapeutic outcome for various treatment modalities for the management of mandibular unicystic ameloblastoma.Materials & Methods:Retrospective analysis of 34 cases from 2005 to 2014 was done and were analysed in terms of demographic profiles, treatment modalities and its efficacy (recurrence in 6 years’ follow up time.Results: The total number of patients was 34. The age ranged from 12 years to 28 years with a mean age of 18.82 years. Gender distribution was 21 males (61.8% and 13 females (38.2%. The location found was 26 (76.5% cases in posterior mandibular region and 8 (23.5% cases in the anterior mandibular region. Size of the lesions was small in 10 (29.4% cases, medium in 18 (52.9% cases and large in 6 (17.6% cases. Perforation of buccal or lingual cortex was present in 6 (17.6% and no preforation in 28 (82.4%. Treatment modalities done was marsupilisation in 6 (17.6% cases, enucleation with peripheral ostectomy with caroney solution in 22 (64.7% cases and resection with safe margin in 6 (17.6% cases. Recurrence occurred in 8 (23.5% cases and no recurrence in 26 (76.5% cases.Conclusion:Enucleation with peripheral ostectomy and Carnoy’s solution is one of the good treatment modality for unicystic ameloblastoma of the mandible whereas complete resection of the mandible with safe margin has low risk of recurrence in long term follow up.

Nanotechnology and regenerative therapeutics in plastic surgery: The next frontier.

Science.gov (United States)

Tan, Aaron; Chawla, Reema; G, Natasha; Mahdibeiraghdar, Sara; Jeyaraj, Rebecca; Rajadas, Jayakumar; Hamblin, Michael R; Seifalian, Alexander M

2016-01-01

The rapid ascent of nanotechnology and regenerative therapeutics as applied to medicine and surgery has seen an exponential rise in the scale of research generated in this field. This is evidenced not only by the sheer volume of papers dedicated to nanotechnology but also in a large number of new journals dedicated to nanotechnology and regenerative therapeutics specifically to medicine and surgery. Aspects of nanotechnology that have already brought benefits to these areas include advanced drug delivery platforms, molecular imaging and materials engineering for surgical implants. Particular areas of interest include nerve regeneration, burns and wound care, artificial skin with nanoelectronic sensors and head and neck surgery. This study presents a review of nanotechnology and regenerative therapeutics, with focus on its applications and implications in plastic surgery. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. All rights reserved.

Usefulness of CT-scan in the diagnosis and therapeutic approach of gallstone ileus: report of two surgically treated cases

OpenAIRE

Michele, Danzi; Luciano, Grimaldi; Massimiliano, Fabozzi; Stefano, Reggio; Roberta, Danzi; Ernesto, Soscia; Bruno, Amato

2013-01-01

Background Gallstone ileus is a rare cause of gastrointestinal obstruction, more frequent in elderly patients, whose treatment is essentially surgical, although some para-surgical and mini-invasive possibilities exist, allowing the solution of such obstructive condition in a completely non-invasive way. Description In our study, after reporting two cases of biliary ileus managed by our surgical division, we will analyze the most suitable diagnostic procedures and the therapeutic approaches to...

Quantitative sensory testing of neuropathic pain patients: potential mechanistic and therapeutic implications.

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Pfau, Doreen B; Geber, Christian; Birklein, Frank; Treede, Rolf-Detlef

2012-06-01

Quantitative sensory testing (QST) is a widely accepted tool to investigate somatosensory changes in pain patients. Many different protocols have been developed in clinical pain research within recent years. In this review, we provide an overview of QST and tested neuroanatomical pathways, including peripheral and central structures. Based on research studies using animal and human surrogate models of neuropathic pain, possible underlying mechanisms of chronic pain are discussed. Clinically, QST may be useful for 1) the identification of subgroups of patients with different underlying pain mechanisms; 2) prediction of therapeutic outcomes; and 3) quantification of therapeutic interventions in pain therapy. Combined with sensory mapping, QST may provide useful information on the site of neural damage and on mechanisms of positive and negative somatosensory abnormalities. The use of QST in individual patients for diagnostic purposes leading to individualized therapy is an interesting concept, but needs further validation.

Pathophysiological aspects and therapeutic approaches of tumoral osteolysis and hypercalcemia.

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Bonjour, J P; Rizzoli, R

1989-01-01

Malignant tumors can affect the integrity of the skeletal tissue and the homeostasis of the two main components of bone mineral, calcium (Ca) and inorganic phosphate (Pi). Various tumoral cell products can increase bone resorption by influencing the number of osteoclasts and/or their activity. These tumoral products could act either directly on bone cells of the osteoblastic or osteoclastic lineages, or indirectly by influencing cells secreting osteotropic factors, such as interleukin-1, tumor necrosis factors, transforming growth factors, and colony-stimulating factor. Among the classical calciotropic hormones, 1,25-dihydroxyvitamin D3 could be implicated in lymphoma. In hypercalcemia of malignancy, an increase in bone resorption is observed in most patients. However, in many cases an increased tubular reabsorption of Ca has been documented as well. This phenomenon when present after adequate rehydration is probably due to the secretion by the tumoral cells of a parathyroid hormone-related peptide (PTHrP). This factor has been recently identified as a protein containing 141 amino acids. This protein or some very close analogs have been shown to be secreted by lung, kidney and also breast carcinoma. Besides increasing bone resorption and stimulating tubular reabsorption of Ca, PTHrP also selectively decreases the tubular reabsorption of Pi, an action that may explain the hypophosphatemia observed in some types of neoplasm. Therapeutically, administration of antiresorbing agents such as clodronate or other bisphosphonates can normalize the increased osteolysis and, if present, the associated elevation in the plasma level of Ca in most cancer patients. However in some cases, wherein the prevailing hypercalcemic mechanism is due to an enhancement in the tubular reabsorption of Ca, other therapeutic means should be associated with the antiosteolytic bisphosphonate therapy.

The Short-term Therapeutic Effect of the Three-part Massotherapy for Insomnia Due to Deficiency of Both the Heart and the Spleen- A Report of 100 Cases

Institute of Scientific and Technical Information of China (English)

无

2007-01-01

Objective: To evaluate the short-term therapeutic effect of the three-part massotherapy on insomnia due to deficiency of both the heart and spleen. Methods: Two hundred cases were randomly divided into a treatment group and a control group, each consisting of 100 cases. Patients in the treatment group were treated with the three-part massotherapy, while those in the control group with oral administration of Guipi Wan (归脾丸Pill for Invigorating the Spleen and Nourishing the Heart). The total clinical therapeutic effects, the total scores of Pittsburgh Sleep Quality Index (PSQI), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) of the treatment group were compared with those of the control group. Results: After the treatment, the total therapeutic effects, PSQI, SAS, and SDS of the two groups all showed significant improvement (P<0.01), and the scores of the treatment group were superior to those of the control group (P<0.01). Conclusion: The three-part massotherapy has definite therapeutic effects on insomnia due to deficiency of both the heart and the spleen, which is safe and easy to operate, and worthy of popularization.

Impact of the scintigraphy of somatostatin receptors upon the therapeutic strategy in patients bearing digestive endocrine tumors

International Nuclear Information System (INIS)

Lebtahi, R.; Cadiot, G.; Genin, R.; Delahaye, N.; Faraggi, M.; Daou, D.; Peker, C.; Migon, M.; Le Guludec, D.

1997-01-01

The scintigraphy of somatostatin receptors (SSR) is a sensible method for detecting the gastroenteric-pancreatic endocrine tumors and their metastases. The aim of this study is to evaluate the clinical impact of the results of SSR in taking patients in therapeutic charge. A hundred and sixty patients bearing biologically and/or histologically proved digestive endocrine tumors were prospectively studied. The patients were classified in 3 groups: group I - 90 patients with no known metastases; group II - 59 patients with liver metastases and group III - 11 patients with known extra-hepatic metastases. The results of the scintigraphy were compared with those of conventional imaging. The following results were obtained: in group 1 (90 patients) the conventional imaging has allowed detecting 53 primitive tumors in 44 patients. The SSR visualized 68% of these sites and has detected 26 supplementary primitive sites in 20 patients and 29 metastatic sites in 25 patients. In group II the scintigraphy has detected 95% of hepatic metastases and revealed 23 new metastasis sites and 18/59 patients. In group III the scintigraphy has detected 11 new sites in 7 patients. The results of scintigraphy modified the patient's classification in 38 cases (24%). The therapeutic strategy was modified for 40 patients (25%). In conclusion, the scintigraphy of somatostatin receptors is able to detect a significant number of digestive endocrine tumors what has important implications for therapeutical planning of the treatment of patients. It must be carried out during pre-therapeutic extension examination of these tumors

Implications for Advanced Nursing Practice in the Use of Therapeutic Touch.

Science.gov (United States)

1993-01-01

care units, where reliance on machines and technology have isolated and depersonalized patients. Before the boon of technology in health care, so...adjunctive therapies. Meehan (1990) recommends TT be taught as part of undergraduate or graduate nursing curricula or in a continuing education program of...staff (ANA, 1986). The CNS may serve as a resource person, preceptor and role model to staff Therapeutic Touch 47 nurses and nursing students , or member

Endoscopic ultrasound in gastroenterology: from diagnosis to therapeutic implications.

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Mekky, Mohamed A; Abbas, Wael A

2014-06-28

Since its advent in 1980, the scope of endoscopic ultrasound (EUS) has grown to include a wide range of indications, and it is now being incorporated as an integral part of everyday practice in the field of gastroenterology. Its use is extending from an adjuvant imaging aid to utilization as a therapeutic tool for various gastrointestinal disorders. EUS was first used to visualize remote organs, such as the pancreas and abdominal lymph nodes. When fine needle aspiration was introduced, the indications for EUS expanded to include tissue sampling for diagnostic purposes. At the same time, the needle can be used to convey a potential therapy to the internal organs, allowing access to remote sites. In this review, we aim to highlight the expanding spectrum of EUS indications and uses in the field of gastroenterology.

Oesophageal Perforation: A diagnostic and therapeutic challenge in a resource limited setting. A report of three cases

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Mahalu William

2011-09-01

Full Text Available Abstract Background Oesophageal perforation is a condition associated with a high mortality. Its management is still controversial with operative treatment being favoured but a shift to conservative management is occurring. Very little exists in medical literature about its management in Sub-Saharan Africa, where the paucity of thoracic surgeons is compounded by limited diagnostic and therapeutic facilities. Case Presentation We report three cases of oesophageal perforation which were all treated conservatively with tube thoracostomy, nil by mouth with feeding gastrostomy, intravenous antibiotics and chest physiotherapy. Two patients achieved oesophageal healing but one died due to severe septicaemia. Conclusion In a resource restricted setting, conservative management which includes enteral nutrition by feeding gastrostomy, tube thoracostomy to drain inter pleural contaminants, intravenous antibiotics and chest physiotherapy is a safe and effective treatment for oesophageal perforations.

Doll therapy: a therapeutic means to meet past attachment needs and diminish behaviours of concern in a person living with dementia--a case study approach.

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Bisiani, Leah; Angus, Jocelyn

2013-07-01

The aim of this research study was to examine the impact of the provision of a lifelike baby doll as a therapeutic tool on the behaviour of a person living with dementia. Specifically, this single case study assessed the potential benefits, if any, of the use of doll therapy in reducing behaviours of concern such as anxiety and agitation that may be associated with observed attachment needs of a person living with dementia. A single case study of a female participant, with moderately advanced Alzheimer's disease, was the subject of this research. The case study used both qualitative and quantitative research design and methodology in data collection and analysis. Demonstrated that doll therapy was a positive intervention for the person living with dementia who was the participant in this research. The findings indicate a reduction in behaviours of concern related to the need for attachment and a considerable decline in levels of anxiety and agitation. There was extensive ongoing improvement in social interaction and communication. This research supports doll therapy as a therapeutic intervention that may be utilized within the ongoing care of some persons with dementia to meet needs for attachment and to reduce behaviours of concern. Despite some controversy on this topic, doll therapy should be considered as a therapeutic approach to further dementia care in light of this positive outcome.

"Forest Grove School District v. T.A." Supreme Court Case: Implications for School Psychology Practice

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Dixon, Shauna G.; Eusebio, Eleazar C.; Turton, William J.; Wright, Peter W. D.; Hale, James B.

2011-01-01

The 2009 "Forest Grove School District v. T.A." United States Supreme Court case could have significant implications for school psychology practice. The Court ruled that the parents of a student with a disability were entitled to private school tuition reimbursement even though T.A. had not been identified with a disability or previously…

MR imaging of metabolic white matter diseases: Therapeutic response

International Nuclear Information System (INIS)

Gebarski, S.S.; Allen, R.

1987-01-01

In metabolic diseases affecting the brain, MR imaging abnormalities include white-matter signal aberrations suggesting myelination delay, dysmyelination and demyelination, pathologic iron storage, and finally, loss of substance usually in a nonspecific pattern. The authors suggest that MR imaging may have therapeutic implications: (1) classic galactosemia - white-matter signal aberration became normal after dietary therapy; (2) phenylketonuria - age- and sex-matched treated and nontreated adolescents showed marked differences in brain volume, with the treated patient's volume nearly normal; (3) maple syrup urine disease - gross white-matter signal aberration became nearly normal after dietary therapy; and (4) hyperglycinemia - relentless progression of white-matter signal aberration and loss of brain substance despite therapy. These data suggest that brain MR imaging may provide a therapeutic index in certain metabolic diseases

Pharmacogenetics approach to therapeutics.

Science.gov (United States)

Koo, Seok Hwee; Lee, Edmund Jon Deoon

2006-01-01

1. Pharmacogenetics refers to the study of genetically controlled variations in drug response. Functional variants caused by single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolising enzymes, transporters, ion channels and drug receptors have been known to be associated with interindividual and interethnic variation in drug response. Genetic variations in these genes play a role in influencing the efficacy and toxicity of medications. 2. Rapid, precise and cost-effective high-throughput technological platforms are essential for performing large-scale mutational analysis of genetic markers involved in the aetiology of variable responses to drug therapy. 3. The application of a pharmacogenetics approach to therapeutics in general clinical practice is still far from being achieved today owing to various constraints, such as limited accessibility of technology, inadequate knowledge, ambiguity of the role of variants and ethical concerns. 4. Drug actions are determined by the interplay of several genes encoding different proteins involved in various biochemical pathways. With rapidly emerging SNP discovery technological platforms and widespread knowledge on the role of SNPs in disease susceptibility and variability in drug response, the pharmacogenetics approach to therapeutics is anticipated to take off in the not-too-distant future. This will present profound clinical, economic and social implications for health care.

Biofuel's energetic paradigm and its implications: A global overview and the Colombian case

International Nuclear Information System (INIS)

Castiblanco Rozo, Carmenza; Hortua Romero, Sonia

2012-01-01

In the last decade biofuels have become a feasible answer given the global need for alternative energy sources. Its increasing demand has been reflected in the expansion of raw materials' crops, with implications in several topics: land use change, ecosystem services relating hydric resources, Greenhouse Gas Emissions (GHG), food security and land property. The objective of this article is a critical analysis of these issues based on a revision of international literature, but also approaching the Colombian case, particularly African oil palm expansion and its social implications. The main results point out that crop expansion will occur in tropical countries. This generates negative impacts that contribute to conflicts around water and land accessibility in regions characterized by their high social and ecosystem vulnerability. Additionally, it is necessary to improve information systems and to refine methodologies and models that allow an adequate evaluation of biofuel production impacts on human well being.

The Evidence for the Spread and Seeding Capacities of the Mutant Huntingtin Protein in in Vitro Systems and Their Therapeutic Implications

Directory of Open Access Journals (Sweden)

Maria Masnata

2017-11-01

Full Text Available Neurodegenerative disorders are not only characterized by specific patterns of cell loss but the presence and accumulation of various pathological proteins—both of which correlate with disease evolution. There is now mounting evidence to suggest that these pathological proteins present with toxic, at times prion-like, properties and can therefore seed pathology in neighboring as well remotely connected healthy neurons as they spread across the brain. What is less clear, at this stage, is how much this actually contributes to, and drives, the core pathogenic events. In this review, we present a comprehensive, up-to-date summary of the reported in vitro studies that support the spreading and seeding capacities of pathological proteins, with an emphasis on mutant huntingtin protein in the context of Huntington's disease, although in vivo work remains to be performed to validate this theory in this particular disease. We have further reviewed these findings in light of their potential implications for the development of novel therapeutic approaches.

[Botulism. Therapeutic management. Apropos of 36 cases].

Science.gov (United States)

Sudre, Y; Becq-Giraudon, B; Boutaud, P h

1975-03-08

Botulism is relatively common in the Vienne department as we have observed 36 cases over a peroid of 7 years. Other French cases, published over the last 10 years, included 10 to 19 cases in the largest series. In a total of 10 series, there were 105 cases. Botulism is caused, in most cases, by eating ham prepared on the farm. It gives rise to the usual clinical picture including paralysis of accommodation, dysphagia, digestive symptoms with abdominal pain and constipation and finally, bladder paralysis. The mild forms are fairly common. We did not observe any severe cases. Our patients were treated in two homogeneous series of 17 cases each ; two patients were given no treatment. Patients treated by sero-anatoxin therapy according to classical methods, evolved towards a cure within 21 days on average. Patients treated by sulfguanidin were cured within 24 days. This study permitted us to confirm that sero-anatoxin therapy is not essential. The disadvantages are the number of injections, the possibility of sometimes fatal hyper-sensitive reactions which, in the opinion of many authors, justifies routine cover with cortisone. This attitude does not seem to us justified owing to the usually benign nature of the botulism. The treatment with sulfaguanidin is well tolerated and is not of any risk to the patient.

Attachment and object relations in patients with narcissistic personality disorder: implications for therapeutic process and outcome.

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Diamond, Diana; Meehan, Kevin B

2013-11-01

This article presents a therapeutic approach for patients with severe personality disorders, transference-focused psychotherapy (TFP), a manualized evidence-based treatment, which integrates contemporary object relations theory with attachment theory and research. Case material is presented from a narcissistic personality disorder (NPD) patient in TFP whose primary presenting problems were in the arena of sexuality and love relations, and whose attachment state of mind showed evidence of oscillation between dismissing and preoccupied mechanisms. Clinical process material is presented to illustrate the tactics and techniques of TFP and how they have been refined for treatment of individuals with NPD. The ways in which conflicts around sexuality and love relations were lived out in the transference is delineated with a focus on the interpretation of devalued and idealized representations of self and others, both of which are key components of the compensatory grandiose self that defensively protects the individual from an underlying sense of vulnerability and imperfection. © 2013 Wiley Periodicals, Inc.

Nanotechnological strategies for nerve growth factor delivery: Therapeutic implications in Alzheimer's disease.

Science.gov (United States)

Faustino, Célia; Rijo, Patrícia; Reis, Catarina Pinto

2017-06-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with amyloid-β peptide misfolding and aggregation. Neurotrophic factors, such as nerve growth factor (NGF), can prevent neuronal damage and rescue the cholinergic neurons that undergo cell death in AD, reverse deposition of extracellular amyloid plaques and improve cognitive deficits. However, NGF administration is hampered by the poor pharmacokinetic profile of the therapeutic protein and its inability to cross the blood-brain barrier, which requires specialised drug delivery systems (DDS) for efficient NGF delivery to the brain. This review covers the main therapeutic approaches that have been developed for NGF delivery targeting the brain, from polymeric implants to gene and cell-based therapies, focusing on the role of nanoparticulate systems for the sustained release of NGF in the brain as a neuroprotective and disease-modifying approach toward AD. Lipid- and polymer-based delivery systems, magnetic nanoparticles and quantum dots are specifically addressed as promising nanotechnological strategies to overcome the current limitations of NGF-based therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ethical dilemmas among nurses as they transition to hospital case management: implications for organizational ethics, part I.

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O'Donnell, Lolita T

2007-01-01

To describe the experiences of ethical concerns by clinical nurses as they transitioned into their new role in hospital case management. Through this study, an attempt was made to explore experiences of ethical concerns and identify the implications for organizational ethics. In this study, nurse case managers practicing in the acute hospital setting, military, not-for-profit community, and teaching hospitals were interviewed. The majority of the nurse case manager participants were engaged in hospital discharge planning and utilization review activities. An interpretive phenomenological approach was used to identify the themes inherent in ethical concerns and articulate them within the context of hospital nurse case management. Fifteen participants were interviewed to obtain a qualitative description of the nurse case managers' lived experiences of ethical dilemmas and how they were resolved. Nurse case managers' perceptions of solutions/options to resolve such ethical dilemmas were explored. As nurses transition into the expanded role of case management in the present healthcare delivery system, they frequently face situations demanding ethical choices and judgments to accommodate diverse patient interests and needs. These ethical decisions required in daily practice in case management represent ethical dilemmas to nurses. The insights derived from the analysis of the interviews have implications for nursing practice, education, policy, ethics, and research; recommendations for organizations employing nurse case managers in terms of recruitment, orientation, training, and continued need for educational support are identified. 1. The clinical decisions required in daily practice of case management represented challenges to the nurses. This highlights the critical role of adequate educational orientation to case management for beginning case managers. 2. Nurse case managers should be cognizant of the "disconnect" that could occur between their obligations to the

Ethical dilemmas among nurses as they transition to hospital case management: implications for organizational ethics, part II.

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O'Donnell, Lolita T

2007-01-01

The purpose of this study was to describe the experiences of ethical concerns by clinical nurses as they transitioned into their new role in hospital case management. Through this study, an attempt was made to explore experiences of ethical concerns and identify the implications for organizational ethics. In this study, nurse case managers practicing in the acute care setting, military, not-for-profit community, and teaching hospitals were interviewed. The majority of the nurse case manager participants were engaged in hospital discharge planning and utilization review activities. An interpretive phenomenological approach was used to identify the themes inherent in ethical concerns and articulate them within the context of hospital nurse case management. Fifteen participants were interviewed to obtain a qualitative description of the nurse case managers' lived experiences of ethical dilemmas and how they were resolved. Nurse case managers' perceptions of solutions/options to resolve such ethical dilemmas were explored. As nurses transition into the expanded role of case management in the present healthcare delivery system, they frequently face situations demanding ethical choices and judgments to accommodate diverse patient interests and needs. These ethical decisions required in daily practice of case management represent ethical dilemmas to nurses. The insights derived from the analysis of the interviews have implications for nursing practice, education, policy, ethics, and research; recommendations for organizations employing nurse case managers in terms of recruitment, orientation, training, and continued need for educational support are identified. 1. The clinical decisions required in daily practice of case management represented challenges to the nurses. This highlights the critical role of adequate educational orientation to case management for beginning case managers. 2. Nurse case managers should be cognizant of the "disconnect" that could occur between

Therapeutic fasting as a potential effective treatment for type 2 diabetes: A 4-month case study

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Michael Ku

2017-12-01

Full Text Available Lifestyle therapy is an integral part of type 2 diabetes (T2D management, but there remains no consensus on an optimal diet. The objective of this study is to evaluate the efficacy of therapeutic fasting as a treatment for T2D. This case follows a male T2D patient treated at the Intensive Dietary Management Clinic in Scarborough, Ontario, over a 4-month period. The patient’s initial fasting regimen consisted of a 24-h fast, three times a week. Over the course of treatment, the patient gradually extended his fasting period, eventually fasting for 42 h, two to three times a week. By the end of treatment, the patient’s weight was reduced by 17.8% and his waist circumference was reduced by 11.0%. In addition, the patient’s glycated haemoglobin levels decreased from 7.7% to 7.2%, and he was able to completely discontinue his insulin treatment, despite over a decade of insulin usage. The patient did not find it difficult to adhere to the fasting schedule and did not experience any hypoglycaemic episodes or other significant adverse effects. These observations suggest that therapeutic fasting may be a viable treatment option for T2D patients.

Angiogenesis and Its Therapeutic Opportunities

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So Young Yoo

2013-01-01

Full Text Available Angiogenesis plays critical roles in human physiology that range from reproduction and fetal growth to wound healing and tissue repair. The sophisticated multistep process is tightly regulated in a spatial and temporal manner by “on-off switch signals” between angiogenic factors, extracellular matrix components, and endothelial cells. Uncontrolled angiogenesis may lead to several angiogenic disorders, including vascular insufficiency (myocardial or critical limb ischemia and vascular overgrowth (hemangiomas, vascularized tumors, and retinopathies. Thus, numerous therapeutic opportunities can be envisaged through the successful understanding and subsequent manipulation of angiogenesis. Here, we review the clinical implications of angiogenesis and discuss pro- and antiangiogenic agents that offer potential therapy for cancer and other angiogenic diseases.

Therapeutic Implications of Targeting Energy Metabolism in Breast Cancer

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Meena K. Sakharkar

2013-01-01

Full Text Available PPARs are ligand activated transcription factors. PPARγ agonists have been reported as a new and potentially efficacious treatment of inflammation, diabetes, obesity, cancer, AD, and schizophrenia. Since cancer cells show dysregulation of glycolysis they are potentially manageable through changes in metabolic environment. Interestingly, several of the genes involved in maintaining the metabolic environment and the central energy generation pathway are regulated or predicted to be regulated by PPARγ. The use of synthetic PPARγ ligands as drugs and their recent withdrawal/restricted usage highlight the lack of understanding of the molecular basis of these drugs, their off-target effects, and their network. These data further underscores the complexity of nuclear receptor signalling mechanisms. This paper will discuss the function and role of PPARγ in energy metabolism and cancer biology in general and its emergence as a promising therapeutic target in breast cancer.

Transcriptional Control of Vascular Smooth Muscle Cell Proliferation by Peroxisome Proliferator-Activated Receptor-γ: Therapeutic Implications for Cardiovascular Diseases

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Florence Gizard

2008-01-01

Full Text Available Proliferation of vascular smooth muscle cells (SMCs is a critical process for the development of atherosclerosis and complications of procedures used to treat atherosclerotic diseases, including postangioplasty restenosis, vein graft failure, and transplant vasculopathy. Peroxisome proliferator-activated receptor (PPAR γ is a member of the nuclear hormone receptor superfamily and the molecular target for the thiazolidinediones (TZD, used clinically to treat insulin resistance in patients with type 2 diabetes. In addition to their efficacy to improve insulin sensitivity, TZD exert a broad spectrum of pleiotropic beneficial effects on vascular gene expression programs. In SMCs, PPARγ is prominently upregulated during neointima formation and suppresses the proliferative response to injury of the arterial wall. Among the molecular target genes regulated by PPARγ in SMCs are genes encoding proteins involved in the regulation of cell-cycle progression, cellular senescence, and apoptosis. This inhibition of SMC proliferation is likely to contribute to the prevention of atherosclerosis and postangioplasty restenosis observed in animal models and proof-of-concept clinical studies. This review will summarize the transcriptional target genes regulated by PPARγ in SMCs and outline the therapeutic implications of PPARγ activation for the treatment and prevention of atherosclerosis and its complications.

Chaperone-mediated autophagy and neurodegeneration: connections, mechanisms, and therapeutic implications.

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Liu, Xiaolei; Huang, Sihua; Wang, Xingqin; Tang, Beisha; Li, Wenming; Mao, Zixu

2015-08-01

Lysosomes degrade dysfunctional intracellular components via three pathways: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Unlike the other two, CMA degrades cytosolic proteins with a recognized KFERQ-like motif in lysosomes and is important for cellular homeostasis. CMA activity declines with age and is altered in neurodegenerative diseases. Its impairment leads to the accumulation of aggregated proteins, some of which may be directly tied to the pathogenic processes of neurodegenerative diseases. Its induction may accelerate the clearance of pathogenic proteins and promote cell survival, representing a potential therapeutic approach for the treatment of neurodegenerative diseases. In this review, we summarize the current findings on how CMA is involved in neurodegenerative diseases, especially in Parkinson's disease.

Developing patient rapport, trust and therapeutic relationships.

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Price, Bob

2017-08-09

Rapport is established at the first meeting between the patient and nurse, and is developed throughout the therapeutic relationship. However, challenges can arise during this process. Initially, nurses can establish trust with the patient through the questions they ask, however, as care progresses, the nurse will be required to demonstrate a commitment to maintaining the patient's psychological well-being. When the therapeutic relationship ends, the nurse should assist the patient to assess progress and plan the next stage of recovery. This article provides three reflective exercises using case study examples to demonstrate how rapport is developed and sustained. Evidence is provided to identify why challenges arise in the therapeutic relationship and how the nurse can ensure they provide care that the patient regards as genuine.

Medical therapeutic effect of hyperthyroidism

International Nuclear Information System (INIS)

Lee, K.B.

1980-01-01

In order to compare the therapeutic effect as well as side effects between antithyroid therapy and radioiodine therapy in hyperthyroidism, the author evaluated 111 cases of hyperthyroidism which were composed of 57 patients with antithyroid treatment, 23 patients with combined treatment comprising of antithyroid and radioactive iodine ( 131 I) and 31 patients with treatment of 131 I alone. (author)

The human gut microbiota and virome: Potential therapeutic implications.

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Scarpellini, Emidio; Ianiro, Gianluca; Attili, Fabia; Bassanelli, Chiara; De Santis, Adriano; Gasbarrini, Antonio

2015-12-01

Human gut microbiota is a complex ecosystem with several functions integrated in the host organism (metabolic, immune, nutrients absorption, etc.). Human microbiota is composed by bacteria, yeasts, fungi and, last but not least, viruses, whose composition has not been completely described. According to previous evidence on pathogenic viruses, the human gut harbours plant-derived viruses, giant viruses and, only recently, abundant bacteriophages. New metagenomic methods have allowed to reconstitute entire viral genomes from the genetic material spread in the human gut, opening new perspectives on the understanding of the gut virome composition, the importance of gut microbiome, and potential clinical applications. This review reports the latest evidence on human gut "virome" composition and its function, possible future therapeutic applications in human health in the context of the gut microbiota, and attempts to clarify the role of the gut "virome" in the larger microbial ecosystem. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

A Case Study with an Identified Bully: Policy and Practice Implications

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Huddleston, Lillie

2011-07-01

Full Text Available Objective: Bullying is a serious public health problem that may include verbal or physical injury as well as social isolation or exclusion. As a result, research is needed to establish a database for policies and interventions designed to prevent bullying and its negative effects. This paper presented a case study that contributed to the literature by describing an intervention for bullies that has implications for research, practice and related policies regarding bullying.Methods: An individualized intervention for an identified bully was implemented using the Participatory Culture-Specific Intervention Model (PCSIM; Nastasi, Moore, & Varjas, 2004 with a seventh-grade middle school student. Ecological and culture-specific perspectives were used to develop and implement the intervention that included psychoeducational sessions with the student and consultation with the parent and school personnel. A mixed methods intervention design was used with the following informants: the target student, the mother of the student, a teacher and the school counselor. Qualitative data included semi-structured interviews with the parent, teacher and student, narrative classroom observations and evaluation/feedback forms filled out by the student and interventionist. Quantitative data included the following quantitative surveys (i.e., Child Posttraumatic Stress Reaction Index [CPTS-RI] and the Behavior Assessment Scale for Children, 2nd Edition. Both qualitative and quantitative data were used to evaluate the acceptability, integrity and efficacy of this intervention.Results: The process of intervention design, implementation and evaluation are described through an illustrative case study. Qualitative and quantitative findings indicated a decrease in internalizing, externalizing and bullying behaviors as reported by the teacher and the mother, and a high degree of acceptability and treatment integrity as reported by multiple stakeholders.Conclusion: This case

[ManNAc, a new therapeutic agent to reduce Angptl4-induced proteinuria in MCD].

Science.gov (United States)

Clément, Lionel; Macé, Camille

2016-01-01

Current therapies used in minimal change disease (MCD) were originally designed to cure other diseases. They are only partially efficient, and present inconvenient side effects. Therefore, understanding the molecular mechanisms implicated in the pathogenesis of proteinuria in MCD could lead to new therapeutic strategies. A new experimental transgenic rat model of human MCD was generated. These NPHS2-Angptl4 transgenic rats over-express two different forms of the glycoprotein Angptl4 from the podocyte. The majority of the protein shows a lack of sialylation that is implicated in the pathogenesis of proteinuria. Supplementation of ManNAc, a precursor of sialic acid, significantly reduces albuminuria in those rats by increasing sialylation of the hyposialylated form of Angptl4. After treatment of the first episode of MCD with glucocorticoids in patients, ManNAc could be used as a maintenance drug, especially to reduce the frequency and intensity of relapse. ManNAc is a promising therapeutic agent for patients with MCD. © 2016 médecine/sciences – Inserm.

Protein and Peptide in Drug Targeting and its Therapeutic Approach

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Raj K. Keservani

2015-09-01

Full Text Available Aim: The main aim of this review article is to provide information like advantages of protein and peptides via different routes of drug administration, targeted to a particular site and its implication in drug delivery system. Methods: To that aim, from the web sites of PubMed, HCAplus, Thomson, and Registry were used as the main sources to perform the search for the most significant research articles published on the subject. The information was then carefully analyzed, highlighting the most important results in the development of protein and peptide drug targeting as well as its therapeutic activity. Results: In recent years many researchers use protein and peptide as a target site of drug by a different delivery system. Proteins and peptides are used as specific and effective therapeutic agents, due to instability and side effects their use is complicated. Protein kinases are important regulators of most, if not all, biological processes. Abnormal activity of proteins and peptides has been implicated in many human diseases, such as diabetes, cancer and neurodegenerative disorders. Conclusions: It is concluded that the protein and peptide were used in drug targeting to specific site and also used in different diseased states like cancer, diabetes, immunomodulating, neurodegenerative effects and antimicrobial activity.

Therapeutic drug monitoring in epilepsy clinic: a multi-disciplinary approach

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Sunee Lertsinudom

2014-12-01

Full Text Available Epilepsy is a common public health problem and needs multi-disciplinary treatment. Therapeutic drug monitoring (TDM is one of step of the multi-disciplinary treatment in epilepsy at Epilepsy clinic, Khon Kaen University (Thailand. The TDM service has been established since 2008. Here, we aimed to study the roles of TDM order and epilepsy control. This is a prospective descriptive study in which data collection was done from January 1 to December 31, 2010, the period when pharmacists took part in assessing the appropriateness in measurement and interpretation of TDM in order to provide suggestions for physicians. The 112 patients under study had an average age of 38.21±15.36 years; 254 samples were collected for therapeutic drug monitoring; phenytoin was submitted mostly for drug monitoring at 46.46%; 44.49% of sub-missions for drug level monitoring were made owing to a suspected sub-therapeutic level. Associations were found between reasons of sending samples for drug level monitoring and the measured drug levels, i.e., 66.67% of drug levels found was so low that they were undetectable in sample for patients’ compliance investigation and 38.94% of the drug levels were found to be sub-therapeutic as for the case where submission of samples was done because of suspected sub-therapeutic level, 40% of the cases were found to be in toxicity range in the cases with suspected over-therapeutic levels and monitoring levels, 58.25% were found to be within the therapeutic range. Pharmacists used the interpreted results in patients’ care by recommending physicians to monitor therapeutic drug closely, to adjust the dosage of drugs, and to recommend checking patients’ compliance in their use of drugs at 56.5, 38.9, and 4.3%, respectively. Physicians’ responses were found to be absolute follow, partial follow and not follow at 77.95, 11.03, and 7.48%, respectively. In conclusion, associations were found between reasons of TDM order and measured drug

Is multiple sclerosis a length-dependent central axonopathy? The case for therapeutic lag and the asynchronous progressive MS hypotheses.

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Giovannoni, Gavin; Cutter, Gary; Sormani, Maria Pia; Belachew, Shibeshih; Hyde, Robert; Koendgen, Harold; Knappertz, Volker; Tomic, Davorka; Leppert, David; Herndon, Robert; Wheeler-Kingshott, Claudia A M; Ciccarelli, Olga; Selwood, David; di Cantogno, Elisabetta Verdun; Ben-Amor, Ali-Frederic; Matthews, Paul; Carassiti, Daniele; Baker, David; Schmierer, Klaus

2017-02-01

Trials of anti-inflammatory therapies in non-relapsing progressive multiple sclerosis (MS) have been stubbornly negative except recently for an anti-CD20 therapy in primary progressive MS and a S1P modulator siponimod in secondary progressive MS. We argue that this might be because trials have been too short and have focused on assessing neuronal pathways, with insufficient reserve capacity, as the core component of the primary outcome. Delayed neuroaxonal degeneration primed by prior inflammation is not expected to respond to disease-modifying therapies targeting MS-specific mechanisms. However, anti-inflammatory therapies may modify these damaged pathways, but with a therapeutic lag that may take years to manifest. Based on these observations we propose that clinically apparent neurodegenerative components of progressive MS may occur in a length-dependent manner and asynchronously. If this hypothesis is confirmed it may have major implications for the future design of progressive MS trials. Copyright © 2016 Elsevier B.V. All rights reserved.

Energy and environmental implications of carbon emission reduction targets: Case of Kathmandu Valley, Nepal

International Nuclear Information System (INIS)

Shrestha, Ram M.; Rajbhandari, Salony

2010-01-01

This paper analyzes the sectoral energy consumption pattern and emissions of CO 2 and local air pollutants in the Kathmandu Valley, Nepal. It also discusses the evolution of energy service demands, structure of energy supply system and emissions from various sectors under the base case scenario during 2005-2050. A long term energy system planning model of the Kathmandu Valley based on the MARKet ALlocation (MARKAL) framework is used for the analyses. Furthermore, the paper analyzes the least cost options to achieve CO 2 emission reduction targets of 10%, 20% and 30% below the cumulative emission level in the base case and also discusses their implications for total cost, technology-mix, energy-mix and local pollutant emissions. The paper shows that a major switch in energy use pattern from oil and gas to electricity would be needed in the Valley to achieve the cumulative CO 2 emission reduction target of 30% (ER30). Further, the share of electricity in the cumulative energy consumption of the transport sector would increase from 12% in the base case to 24% in the ER30 case.

Adverse drug events associated with vitamin K antagonists: factors of therapeutic imbalance

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El-Helou N

2013-03-01

Full Text Available Nancy El-Helou, Amal Al-Hajje, Rola Ajrouche, Sanaa Awada, Samar Rachidi, Salam Zein, Pascale SalamehClinical and Epidemiological Research Laboratory, Faculty of Pharmacy, Lebanese University, Beirut, LebanonBackground: Adverse drug events (ADE occur frequently during treatment with vitamin K antagonists (AVK and contribute to increase hemorrhagic risks.Methods: A retrospective study was conducted over a period of 2 years. Patients treated with AVK and admitted to the emergency room of a tertiary care hospital in Beirut were included. The aim of the study was to identify ADE characterized by a high international normalized ratio (INR and to determine the predictive factors responsible for these events. Statistical analysis was performed with the SPSS statistical package.Results: We included 148 patients. Sixty-seven patients (47.3% with an INR above the therapeutic range were identified as cases. The control group consisted of 81 patients (54.7% with an INR within the therapeutic range. Hemorrhagic complications were observed in 53.7% of cases versus 6.2% of controls (P < 0.0001. No significant difference was noticed between cases and controls regarding the indication and the dose of AVK. Patients aged over 75 years were more likely to present an INR above the therapeutic range (58.2%, P = 0.049. Recent infection was present in 40.3% of cases versus 6.2% of controls (P < 0.0001 and hypoalbuminemia in 37.3% of cases versus 6.1% of controls (P < 0.0001. Treatment with antibiotics, amiodarone, and anti-inflammatory drugs were also factors of imbalance (P < 0.0001.Conclusion: Many factors may be associated with ADE related to AVK. Monitoring of INR and its stabilization in the therapeutic range are important for preventing these events.Keywords: adverse drug events, vitamin K antagonists, bleeding risks, therapeutic imbalance

automated (centrifugal) therapeutic plasma exchange option for ...

African Journals Online (AJOL)

Therapeutic plasma exchange (TPE) is performed frequently and effectively in developed countries, whereas the reverse is the case in developing countries. Guillain‑Barre syndrome (GBS), synonymous with acute inflammatory demyelinating polyneuropathy, is an important indication for TPE, but this is rarely administered ...

Astroglial networks and implications for therapeutic neuromodulation of epilepsy.

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Witcher, Mark R; Ellis, Thomas L

2012-01-01

Epilepsy is a common chronic neurologic disorder affecting approximately 1% of the world population. More than one-third of all epilepsy patients have incompletely controlled seizures or debilitating medication side effects in spite of optimal medical management. Medically refractory epilepsy is associated with excess injury and mortality, psychosocial dysfunction, and significant cognitive impairment. Effective treatment options for these patients can be limited. The cellular mechanisms underlying seizure activity are incompletely understood, though we here describe multiple lines of evidence supporting the likely contribution of astroglia to epilepsy, with focus on individual astrocytes and their network functions. Of the emerging therapeutic modalities for epilepsy, one of the most intriguing is the field of neuromodulation. Neuromodulatory treatment, which consists of administering electrical pulses to neural tissue to modulate its activity leading to a beneficial effect, may be an option for these patients. Current modalities consist of vagal nerve stimulation, open and closed-loop stimulation, and transcranial magnetic stimulation. Due to their unique properties, we here present astrocytes as likely important targets for the developing field of neuromodulation in the treatment of epilepsy.

Trichogram To Monitor Therapeutic Benefit In Hair Loss

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Uppal Monica

2004-01-01

Full Text Available Trichogram is a method of quantifying hair. We report 3 cases of diffuse hair loss of varying etiology in whom the improvement after therapeutic intervention could be objectively documented using trichogram.

The Epigenome as a therapeutic target for Parkinson's disease

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Shane V Hegarty

2016-01-01

Full Text Available Parkinson's disease (PD is a common, progressive neurodegenerative disease characterised by degeneration of nigrostriatal dopaminergic neurons, aggregation of α-synuclein and motor symptoms. Current dopamine-replacement strategies provide symptomatic relief, however their effectiveness wear off over time and their prolonged use leads to disabling side-effects in PD patients. There is therefore a critical need to develop new drugs and drug targets to protect dopaminergic neurons and their axons from degeneration in PD. Over recent years, there has been robust evidence generated showing that epigenetic dysregulation occurs in PD patients, and that epigenetic modulation is a promising therapeutic approach for PD. This article first discusses the present evidence implicating global, and dopaminergic neuron-specific, alterations in the methylome in PD, and the therapeutic potential of pharmacologically targeting the methylome. It then focuses on another mechanism of epigenetic regulation, histone acetylation, and describes how the histone acetyltransferase (HAT and histone deacetylase (HDAC enzymes that mediate this process are attractive therapeutic targets for PD. It discusses the use of activators and/or inhibitors of HDACs and HATs in models of PD, and how these approaches for the selective modulation of histone acetylation elicit neuroprotective effects. Finally, it outlines the potential of employing small molecule epigenetic modulators as neuroprotective therapies for PD, and the future research that will be required to determine and realise this therapeutic potential.

Power in the hypnotic relationship: therapeutic or abusive?

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Walling, D P; Levine, R E

1997-01-01

The unique relationship between hypnotist and subject has been theorized as one explanation for the effectiveness of hypnosis. This relationship carries a power differential, present in most therapeutic relationships, but accentuated by hypnosis. The power differential is sometimes perceived as the ability of the hypnotist to control the subject. Perceptions of hypnosis offered by stage hypnotists, the popular media, and some clinicians perpetuate the notion that the hypnotist has the ability to exert undue influence upon the client. The present article examines the relationship between hypnotist and subject focusing on issues of power and control. The authors examine the unique dynamics accompanying the use of hypnosis and their impact on the therapeutic dyad. Evidence is offered demonstrating the power differential, and how this differential can serve as either a positive or negative agent of change. Therapists should be aware of the dynamics created by using hypnosis. Implications for training therapists in the use of hypnosis are suggested.

The pragmatics of therapeutic interaction: an empirical study.

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Lepper, Georgia

2009-10-01

The research reported in this article aims to demonstrate a method for the systematic study of the therapist/patient interaction in psychoanalytic psychotherapy, drawing upon the tradition and methods of 'pragmatics'--the study of language in interaction. A brief introduction to the discipline of pragmatics demonstrates its relevance to the contemporary focus of clinical theory on the here-and-now dynamics of the relationship between analyst and patient. This is followed by a detailed study of five segments from the transcript of a therapeutic dialogue, drawn from a brief psychoanalytic psychotherapy, in which therapist and patient negotiate the meaning of the patient's symptom: Is it psychosomatic? The research seeks to show how the therapeutic process can be observed and studied as an interactional achievement, grounded in general and well-studied procedures through which meaning is intersubjectively developed and shared. Implications of the analysis for clinical theory and practice, and further research, are discussed.

Some ethical issues in feminist-oriented therapeutic groups for women.

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Lakin, M

1991-04-01

Review of the origins of group psychotherapy reveals concerns with social as well as with personal "psychopathology." Thus, group processes have been mobilized for curative or change purposes for ideological as well as individual therapeutic goals. Psychopolitical as well as personal change are the goals for some groups. The ethical problem stems from a persistent assumption that the group's processes are inherently benign and curative and beneficial to individual participants. A more sophisticated understanding takes into account their essential neutrality and their potential use (or abuse) for purposes of ideological persuasion that may or may not be personally therapeutic. As in other ethically implicated issues in the psychotherapies, the question becomes one of treatment versus exploitation, or therapy for the individual versus recruitment on behalf of a cause.

Combination of a Flipped Classroom Format and a Virtual Patient Case to Enhance Active Learning in a Required Therapeutics Course

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Lichvar, Alicia Beth; Hedges, Ashley; Benedict, Neal J.

2016-01-01

Objective. To design and evaluate the integration of a virtual patient activity in a required therapeutics course already using a flipped-classroom teaching format. Design. A narrative-branched, dynamic virtual-patient case was designed to replace the static written cases that students worked through during the class, which was dedicated to teaching the complications of liver disease. Students completed pre- and posttests before and after completing the virtual patient case. Examination scores were compared to those in the previous year. Assessment. Students’ posttest scores were higher compared to pretest scores (33% vs 50%). Overall median examination scores were higher compared to the historical control group (70% vs 80%), as well as scores on questions assessing higher-level learning (67% vs 83%). A majority of students (68%) felt the virtual patient helped them apply knowledge gained in the pre-class video lecture. Students preferred this strategy to usual in-class activities (33%) or indicated it was of equal value (37%). Conclusion. The combination of a pre-class video lecture with an in-class virtual patient case is an effective active-learning strategy. PMID:28179724

Combination of a Flipped Classroom Format and a Virtual Patient Case to Enhance Active Learning in a Required Therapeutics Course.

Science.gov (United States)

Lichvar, Alicia Beth; Hedges, Ashley; Benedict, Neal J; Donihi, Amy C

2016-12-25

Objective. To design and evaluate the integration of a virtual patient activity in a required therapeutics course already using a flipped-classroom teaching format. Design. A narrative-branched, dynamic virtual-patient case was designed to replace the static written cases that students worked through during the class, which was dedicated to teaching the complications of liver disease. Students completed pre- and posttests before and after completing the virtual patient case. Examination scores were compared to those in the previous year. Assessment. Students' posttest scores were higher compared to pretest scores (33% vs 50%). Overall median examination scores were higher compared to the historical control group (70% vs 80%), as well as scores on questions assessing higher-level learning (67% vs 83%). A majority of students (68%) felt the virtual patient helped them apply knowledge gained in the pre-class video lecture. Students preferred this strategy to usual in-class activities (33%) or indicated it was of equal value (37%). Conclusion. The combination of a pre-class video lecture with an in-class virtual patient case is an effective active-learning strategy.

[Therapeutic use of cannabis derivatives].

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Benyamina, Amine; Reynaud, Michel

2014-02-01

The therapeutic use of cannabis has generated a lot of interest in the past years, leading to a better understanding of its mechanisms of action. Countries like the United States and Canada have modified their laws in order to make cannabinoid use legal in the medical context. It's also the case in France now, where a recent decree was issued, authorizing the prescription of medication containing "therapeutic cannabis" (decree no. 2013-473, June 5, 2013). Cannabinoids such as dronabinol, Sativex and nabilone have been tested for the treatment of acute and chronic pain. These agents are most promising to relieve chronic pain associated with cancer, with human immunodeficiency virus infection and with multiple sclerosis. However, longer-term studies are required to determine potential long-term adverse effects and risks of misuse and addiction.

Immunohistochemical investigations and introduction of new therapeutic strategies in scleromyxoedema: Case report

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Altmeyer Peter

2004-09-01

Full Text Available Abstract Background Scleromyxoedema is a rare chronic skin disease of obscure origin, which may often be associated with severe internal co-morbidity. Even though different casuistic treatment modalities have been described, to date, curing still seems to be impossible. Case presentation We report a 44-year-old Caucasian female presenting with remarkable circumscribed, erythematous to skin-coloured, indurated skin eruptions at the forehead, arms, shoulders, legs and the gluteal region. Routine histology and Alcian blue labelling confirmed a massive deposition of acid mucopolysaccharides. Immunohistochemical investigations revealed proliferating fibroblasts and a discrete lymphocytic infiltration as well as increased dermal expression of MIB-1+ and anti-mastcell-tryptase+ cells. Bone marrow biopsies confirmed a monoclonal gammopathy of undetermined significance without morphological characteristics of plasmocytoma; immunofixation unveiled the presence of IgG-kappa paraproteins. Conclusions Taking all data into account, our patient exhibited a complex form of lichen mxyoedematosus, which could most likely be linked a variant of scleromyxoedema. Experimental treatment with methotrexate resulted in a stabilisation of clinical symptoms but no improvement after five months of therapy. A subsequent therapeutic attempt by the use of medium-dose ultraviolet A1 cold-light photomonotherapy led to a further stabilisation of clinical symptoms, but could not induce a sustained amelioration of skin condition.

Clinical implications of antiretroviral drug interactions with warfarin: a case-control study.

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Esterly, John S; Darin, Kristin M; Gerzenshtein, Lana; Othman, Fidah; Postelnick, Michael J; Scarsi, Kimberly K

2013-06-01

Warfarin, a frequently prescribed anticoagulant with a narrow therapeutic index, is susceptible to drug-drug interactions with antiretroviral therapy (ART). This study compared the warfarin maintenance dose (WMD) between patients receiving and not receiving ART and evaluated predictors of warfarin dosage among those on ART. This was a case-control (1:2) study. Cases were HIV-infected patients receiving warfarin and protease inhibitor (PI)- and/or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Controls were randomly selected HIV-uninfected patients receiving warfarin. The WMD was compared between cases and controls and between cases on varying ART regimens. Bivariate comparisons were performed and a linear regression model was developed to identify predictors of WMD. We identified 18 case and 36 control patients eligible for inclusion. Cases were younger than controls (mean age: 45.8 versus 63.1 years, P African American (50.0% versus 22.2%, P=0.04). ART was classified as PI-based (n=9), NNRTI-based (n=7) and PI + NNRTI-based (n=2). The WMD (mean ± SD) differed between cases and controls (8.6  ±  3.4 mg versus 5.1 ± 1.5 mg, P ART regimens (PI: 8.8  ±  4.5 mg; NNRTI: 8.6   ± 1.8 mg; PI + NNRTI: 7.3  ±  3.3 mg; P = 0.86). Race and ritonavir dose were independent predictors of WMD, predicting an increase of 3.9 mg (95% CI: 0.88-6.98, P = 0.02) if a patient was African American or 3.7 mg (95% CI: 0.53-6.89, P = 0.03) if the total daily ritonavir dose was 200 mg. The required WMD was significantly higher in patients receiving ART. Prompt dose titration to achieve a higher WMD with vigilant monitoring may be required due to these drug-drug interactions.

Implications of case managers' perceptions and attitude on safety of home-delivered care.

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Jones, Sarahjane

2015-12-01

Perceptions on safety in community care have been relatively unexplored. A project that sought to understand the multiple perspectives on safety in the NHS case-management programme was carried out in relation to the structure, process, and outcome of care. This article presents a component of the nursing perspective that highlights an important element in the structure of nursing care that could potentially impede the nurses' ability to be fully effective and safe. A single case study of the case-management programme was undertaken. Three primary care organisations from three strategic health authorities participated, and three focus groups were conducted (one within each organisation). In total, 17 case management nurses participated. Data were audiotaped and transcribed verbatim and subjected to framework analysis. Nursing staff attitudes were identified as a structure of care that influence safety outcomes, particularly their perceptions of the care setting and the implications it has on their role and patient behaviour. Greater understanding of the expected role of the community nurse is necessary, and relevant training is required for nurses to be successful in empowering patients to perform more safely. In addition, efforts need to be made to improve patients' trust in the health-care system to prevent harm and promote more effective utilisation of resources.

Positive results of serological tests for syphilis in pregnancy – diagnostic and therapeutic problems, report of two cases

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Marta Koper

2015-06-01

Full Text Available Introduction. Undiagnosed and untreated syphilis in pregnancy may result in subsequent complications: early fetal loss, stillbirth, low birth weight of infants and newborns with congenital syphilis. Objective. To analyze diagnostic and therapeutic dilemmas of positive results of serological tests for syphilis (STS in pregnancy. Case reports. We present two cases of pregnant women, hospitalized in our department due to positive results of serological tests for syphilis, performed during the antenatal visit. On the basis of patients' history, physical examination and STS results, early latent syphilis was diagnosed in the first patient; biological false positive reactions were considered in the second one. Both patients received procaine penicillin treatment. Conclusions. Screening for syphilis in pregnancy as a part of antenatal care and appropriate treatment with penicillin are the most effective interventions to prevent complications of syphilis in pregnancy. It is also important to adapt modern European Guidelines for management of syphilis to Polish conditions.

Male Contraception: Research, New Methods, and Implications for Marginalized Populations.

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Plana, Olivia

2017-07-01

The majority of research on contraception has focused on manipulating the female reproductive system. Recent studies have identified novel contraceptives for males, including hormonal- and nonhormonal-based therapeutics. Although these new contraceptives are still undergoing clinical trials, their development and potential future use in society necessitate serious consideration of their implications for reproductive health. Through my analysis of the research conducted on male contraception over time and the current therapeutics available, it is clear that male contraception has the potential to shift societal gender dynamics and provide males with greater control over their own reproduction. This article also identifies the implications of these novel contraceptives for marginalized populations, especially men of color and men of lower socioeconomic positions. To overcome barriers to contraception among these populations, public policy efforts are needed in order to motivate the development of programs that facilitate coverage of these new male contraceptives by health plans and to increase their availability to underserved communities. Health care providers will be responsible for educating patients about these novel male contraception options and the need to continue using existing methods (e.g., condoms) in order to prevent sexually transmitted infections. This article analyzes the research conducted on male contraception and identifies the implications of these novel therapeutics for marginalized groups of men in the United States to identify the interventions that will be necessary to help ensure that all men have access to these promising scientific innovations.

Histopathological study of ocular erythema nodosum leprosum and post-therapeutic scleral perforation: A case report

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Rathinam S

2008-01-01

Full Text Available Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae , clinically present either as tuberculoid, borderline or lepromatous type. Erythema nodosum leprosum (ENL is an acute humoral response in the chronic course of lepromatous leprosy. Although very severe ENL reactions are known in systemic leprosy, such severity is rare in ocular tissues. A leprosy uveitis patient suffered from a severe form of post-therapeutic ENL reaction which resulted in perforation of the globe at the site of preexisting subconjunctival leproma. Painful blind eye was enucleated. Histopathological study revealed infiltration of numerous polymorphs and macrophages packed with acid-fast bacilli in the conjunctiva, cornea, ciliary body, ora serrata and sclera. A profuse influx of neutrophils on a background of macrophages packed with M. leprae confirmed the ocular ENL reaction. This case is reported to alert the ophthalmologists to a rare ocular complication of ENL.

Climate change and energy: The implications for the Spanish case; Cambio Climatico y Energia: Impliacaciones reciprocas en el caso Espanol

Energy Technology Data Exchange (ETDEWEB)

Perez Arriaga, J. I.

2007-07-01

This paper examines the mutual implications between the climate change problem and the actual energy-at-a-crossroads situation of the unsustainable world energy model. The implications for the Spanish case are studied as a case example. The paper provides a brief review of the scientific evidence on climate change, analyzes the causes of the present energy dilemma and characterizes the problem to be addressed. The principal challenge for the future climate regime is to identify the nature and level of commitment that will provide sufficient incentives for all countries, with such a diversity of interests. The paper also exposes the most plausible framework for the future climate regime, the basic components of such a regime, the role to be played by the major stake holders and some guidelines for future negotiations. (Author)

Astroglial networks and implications for therapeutic neuromodulation of epilepsy

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Mark R Witcher

2012-08-01

Full Text Available Epilepsy is a common chronic neurologic disorder affecting approximately 1 percent of the world population. More than one-third of all epilepsy patients have incompletely controlled seizures or debilitating medication side effects in spite of optimal medical management. Medically refractory epilepsy is associated with excess injury and mortality, psychosocial dysfunction, and significant cognitive impairment. Effective treatment options for these patients can be limited. The cellular mechanisms underlying seizure activity are incompletely understood, though we here describe multiple lines of evidence supporting the likely contribution of astroglia to epilepsy, with focus on individual astrocytes and their network functions. Of the emerging therapeutic modalities for epilepsy, one of the most intriguing is the field of neuromodulation. Neuromodulatory treatment, which consists of administering electrical pulses to neural tissue to modulate its activity leading to a beneficial effect, may be an option for these patients. Current modalities consist of vagal nerve stimulation, open and closed loop stimulation, and transcranial magnetic stimulation. Due to their unique properties, we here present astrocytes as likely important targets for the developing field of neuromodulation in the treatment of epilepsy.

A rare case of Shewanella putrefaciens bacteremia in a patient of road traffic accident

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Ritesh Ranjan

2017-01-01

Full Text Available Shewanella putrefaciens rarely causes human infection. These are mostly found in environment and food stuffs. Shewanella are often found in mixed culture. It has been implicated in cellulitis, otitis media, and septicemia. It may be found in respiratory tract, urine, feces, and pleural fluid. There is no definite guideline for therapeutic option. In general, these are susceptible to various antimicrobial agents but are often resistant to penicillin and cephalothin. We report a rare case of bacteremia by S. putrefaciens in a patient of head injury with polytrauma after a road traffic accident.

Mathematical modeling of tumor-induced immunosuppression by myeloid-derived suppressor cells: Implications for therapeutic targeting strategies.

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Shariatpanahi, Seyed Peyman; Shariatpanahi, Seyed Pooya; Madjidzadeh, Keivan; Hassan, Moustapha; Abedi-Valugerdi, Manuchehr

2018-04-07

Myeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that are generated and accumulated during the tumor development. MDSCs strongly suppress the anti-tumor immunity and provide conditions for tumor progression and metastasis. In this study, we present a mathematical model based on ordinary differential equations (ODE) to describe tumor-induced immunosuppression caused by MDSCs. The model consists of four equations and incorporates tumor cells, cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs. We also provide simulation models that evaluate or predict the effects of anti-MDSC drugs (e.g., l-arginine and 5-Fluorouracil (5-FU)) on the tumor growth and the restoration of anti-tumor immunity. The simulated results obtained using our model were in good agreement with the corresponding experimental findings on the expansion of splenic MDSCs, immunosuppressive effects of these cells at the tumor site and effectiveness of l-arginine and 5-FU on the re-establishment of antitumor immunity. Regarding this latter issue, our predictive simulation results demonstrated that intermittent therapy with low-dose 5-FU alone could eradicate the tumors irrespective of their origins and types. Furthermore, at the time of tumor eradication, the number of CTLs prevailed over that of cancer cells and the number of splenic MDSCs returned to the normal levels. Finally, our predictive simulation results also showed that the addition of l-arginine supplementation to the intermittent 5-FU therapy reduced the time of the tumor eradication and the number of iterations for 5-FU treatment. Thus, the present mathematical model provides important implications for designing new therapeutic strategies that aim to restore antitumor immunity by targeting MDSCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Leaving patients to their own devices? Smart technology, safety and therapeutic relationships.

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Ho, Anita; Quick, Oliver

2018-03-06

This debate article explores how smart technologies may create a double-edged sword for patient safety and effective therapeutic relationships. Increasing utilization of health monitoring devices by patients will likely become an important aspect of self-care and preventive medicine. It may also help to enhance accurate symptom reports, diagnoses, and prompt referral to specialist care where appropriate. However, the development, marketing, and use of such technology raise significant ethical implications for therapeutic relationships and patient safety. Drawing on lessons learned from other direct-to-consumer health products such as genetic testing, this article explores how smart technology can also pose regulatory challenges and encourage overutilization of healthcare services. In order for smart technology to promote safer care and effective therapeutic encounters, the technology and its utilization must be safe. This article argues for unified regulatory guidelines and better education for both healthcare providers and patients regarding the benefits and risks of these devices.

Discovery and design of carbohydrate-based therapeutics.

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Cipolla, Laura; Araújo, Ana C; Bini, Davide; Gabrielli, Luca; Russo, Laura; Shaikh, Nasrin

2010-08-01

Till now, the importance of carbohydrates has been underscored, if compared with the two other major classes of biopolymers such as oligonucleotides and proteins. Recent advances in glycobiology and glycochemistry have imparted a strong interest in the study of this enormous family of biomolecules. Carbohydrates have been shown to be implicated in recognition processes, such as cell-cell adhesion, cell-extracellular matrix adhesion and cell-intruder recognition phenomena. In addition, carbohydrates are recognized as differentiation markers and as antigenic determinants. Due to their relevant biological role, carbohydrates are promising candidates for drug design and disease treatment. However, the growing number of human disorders known as congenital disorders of glycosylation that are being identified as resulting from abnormalities in glycan structures and protein glycosylation strongly indicates that a fast development of glycobiology, glycochemistry and glycomedicine is highly desirable. The topics give an overview of different approaches that have been used to date for the design of carbohydrate-based therapeutics; this includes the use of native synthetic carbohydrates, the use of carbohydrate mimics designed on the basis of their native counterpart, the use of carbohydrates as scaffolds and finally the design of glyco-fused therapeutics, one of the most recent approaches. The review covers mainly literature that has appeared since 2000, except for a few papers cited for historical reasons. The reader will gain an overview of the current strategies applied to the design of carbohydrate-based therapeutics; in particular, the advantages/disadvantages of different approaches are highlighted. The topic is presented in a general, basic manner and will hopefully be a useful resource for all readers who are not familiar with it. In addition, in order to stress the potentialities of carbohydrates, several examples of carbohydrate-based marketed therapeutics are given

Management of hypertriglyceridemia induced acute pancreatitis and therapeutic plasmapheresis : Report of nine cases and review of literature.

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Uyar, S; Harmandar, F; Kök, M; Taș, Z; Dolu, S; Tokuç, A; Köker, G; Görar, S; Çekin, A H

2017-01-01

Hypertriglyceridemia is one of the rare causes of the acute pancreatitis. The prevalance of hypertriglyceridemia has increased recently due to the changing eating habits, sedentary lifestyle, alcohol consumption, obesity and concomitant diabetes mellitus. Therefore, the frequency of the acute pancreatitis due to hypertriglyceridemia may increase in coming years. Diagnosis of the acute pancreatitis by hypertriglyceridemia can be overlooked easily and may be very severe if untreated accurately on time. In addition to the standard management of pancreatitis, specific treatment for hypertriglyceridemia that is insulin, heparin and anti-hypertriglyceridemic drugs are used. Therapeutic plasmapheresis is the last treatment option and seems the most effective one in this subject through developing device and membrane technologies when we review the current literature. Not only triglycerides but also proinflammatory cytokines and adhesion molecules that play an active role in pathogenesis are removed by plasmapheresis. So, the effectiveness of treatment appears promising. However, the exact pathophysiology of hypertriglyceridemia-induced pancreatitis could not be fully understood and the majority of published experience comes from the case reports and the benefit of randomized clinical trials is not available. Therefore, there are no data about what are the exact indications and when we start therapeutic plasmapheresis in literature. This manuscript describes our hospital experience with treatment options and analyzes reports published recently about plasmapheresis as a treatment modality for hypertriglyceridemia induced acute pancreatitis. © Acta Gastro-Enterologica Belgica.

Piercing and Tattoos in Adolescents: Legal and Medico-legal Implications.

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Conti, Adelaide; Bin, Paola; Casella, Claudia; Capasso, Emanuele; Fedeli, Piergiorgio; Salzano, Francesco Antonio; Terracciano, Lucia; Piras, Mauro

2018-01-01

Non-therapeutic body modification interventions are permitted within the limits of the use of one's own body that can be specified in the legal system. The authors take into consideration Italian regulation on tattooing and piercing, in particular in relation to adolescents. In Italy, several regions have therefore issued acts aimed at regulating the activities of tattoo and piercing also in reference to minors. Discussion. With regard to minors, the rules taken into account set precise limits in relation to the age criterion and subordinate the implementation of such practices to the provision of consent by legal representatives. If such practices are of an aesthetic nature, we cannot avoid considering the implications they have on health protection, and then adopt appropriate measures to protect the person who intends to undergo them, particularly in the case of minors.

Piercing and Tattoos in Adolescents: Legal and Medico-legal Implications

Science.gov (United States)

Conti, Adelaide; Bin, Paola; Casella, Claudia; Capasso, Emanuele; Fedeli, Piergiorgio; Salzano, Francesco Antonio; Terracciano, Lucia; Piras, Mauro

2018-01-01

Abstract Non-therapeutic body modification interventions are permitted within the limits of the use of one’s own body that can be specified in the legal system. The authors take into consideration Italian regulation on tattooing and piercing, in particular in relation to adolescents. Results In Italy, several regions have therefore issued acts aimed at regulating the activities of tattoo and piercing also in reference to minors. Discussion. With regard to minors, the rules taken into account set precise limits in relation to the age criterion and subordinate the implementation of such practices to the provision of consent by legal representatives. Conclusion If such practices are of an aesthetic nature, we cannot avoid considering the implications they have on health protection, and then adopt appropriate measures to protect the person who intends to undergo them, particularly in the case of minors. PMID:29675481

Progranulin as a biomarker and potential therapeutic agent.

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Abella, Vanessa; Pino, Jesús; Scotece, Morena; Conde, Javier; Lago, Francisca; Gonzalez-Gay, Miguel Angel; Mera, Antonio; Gómez, Rodolfo; Mobasheri, Ali; Gualillo, Oreste

2017-10-01

Progranulin is a cysteine-rich secreted protein with diverse pleiotropic actions and participates in several processes, such as inflammation or tumorigenesis. Progranulin was first identified as a growth factor and, recently, it was characterised as an adipokine implicated in obesity, insulin resistance and rheumatic disease. At a central level, progranulin acts as a neurotropic and neuroprotective factor and protects from neural degeneration. In this review, we summarise the most recent research advances concerning the potential role of progranulin as a therapeutic target and biomarker in cancer, neurodegenerative and inflammatory diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recognition and Distance in Therapeutic Education: A Swedish Case Study on Ethical Qualities within Life Competence Education

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Irisdotter Aldenmyr, Sara

2013-01-01

Lately, in educational research and debate, there have been discussions on a trend sometimes named as a "therapeutic turn" in education. Mindfulness-oriented activities represent one therapeutic approach in education, aiming for virtues such as patience and trust. A large part of the critical viewpoints on therapeutic education among…

Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in Perinatal Brain Injury

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Bryan Leaw

2017-07-01

Full Text Available Injury to the fragile immature brain is implicated in the manifestation of long-term neurological disorders, including childhood disability such as cerebral palsy, learning disability and behavioral disorders. Advancements in perinatal practice and improved care mean the majority of infants suffering from perinatal brain injury will survive, with many subtle clinical symptoms going undiagnosed until later in life. Hypoxic-ischemia is the dominant cause of perinatal brain injury, and constitutes a significant socioeconomic burden to both developed and developing countries. Therapeutic hypothermia is the sole validated clinical intervention to perinatal asphyxia; however it is not always neuroprotective and its utility is limited to developed countries. There is an urgent need to better understand the molecular pathways underlying hypoxic-ischemic injury to identify new therapeutic targets in such a small but critical therapeutic window. Mitochondria are highly implicated following ischemic injury due to their roles as the powerhouse and main energy generators of the cell, as well as cell death processes. While the link between impaired mitochondrial bioenergetics and secondary energy failure following loss of high-energy phosphates is well established after hypoxia-ischemia (HI, there is emerging evidence that the roles of mitochondria in disease extend far beyond this. Indeed, mitochondrial turnover, including processes such as mitochondrial biogenesis, fusion, fission and mitophagy, affect recovery of neurons after injury and mitochondria are involved in the regulation of the innate immune response to inflammation. This review article will explore these mitochondrial pathways, and finally will summarize past and current efforts in targeting these pathways after hypoxic-ischemic injury, as a means of identifying new avenues for clinical intervention.

Creativity and improvisation as therapeutic tools within music therapy.

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Tomaino, Concetta M

2013-11-01

The neuroscience of creativity and music improvisation is a fascinating topic and one with strong implications for clinical music therapy. Music therapists are trained to use musical improvisation as a means to bring their clients into deeper therapeutic relationship as well as free up any inhibitions or limitations that may block recovery. Could recent fMRI studies of jazz musicians showing areas of brain activation during music improvisation provide a new framework to understand underlying mechanisms at work with neurologically impaired individuals? © 2013 New York Academy of Sciences.

Specific RSK kinase inhibition by dibenzyl trisulfide and implication for therapeutic treatment of cancer.

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Lowe, Henry I C; Facey, Caroline O B; Toyang, Ngeh J; Bryant, Joseph L

2014-04-01

The Jamaican "Guinea Hen Weed" (Petiveria alliacea L.) plant has been traditionally used in folklore medicine to treat a variety of diseases including cancer. In the present study we investigated on the therapeutic feasibility of dibenzyl trisulfide (DTS) (isolated from the Jamaican Guinea Hen Weed) as a potent small-molecule kinase inhibitor to treat cancer. We investigated the inhibitory effects of DTS against a large panel of kinases using a well-established competitive binding assay. Cell proliferation data were obtained using the WST-1 colorimetric assay. DTS inhibited the activity of the C-terminal kinase domain of RSK1 (80% compared to control) with a Kd of 1.3 μM. Anti-proliferative effects of DTS were observed in small lung, pancreatic, breast, and prostate cancer cells with IC50 values ranging from 0.34-0.84 μM. We have identified DTS as a highly selective and isoform-specific RSK1 kinase inhibitor with broad cancer therapeutic potential.

Graphene-based platforms for cancer therapeutics

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Patel, Sunny C; Lee, Stephen; Lalwani, Gaurav; Suhrland, Cassandra; Chowdhury, Sayan Mullick; Sitharaman, Balaji

2016-01-01

Graphene is a multifunctional carbon nanomaterial and could be utilized to develop platform technologies for cancer therapies. Its surface can be covalently and noncovalently functionalized with anticancer drugs and functional groups that target cancer cells and tissue to improve treatment efficacies. Furthermore, its physicochemical properties can be harnessed to facilitate stimulus responsive therapeutics and drug delivery. This review article summarizes the recent literature specifically focused on development of graphene technologies to treat cancer. We will focus on advances at the interface of graphene based drug/gene delivery, photothermal/photodynamic therapy and combinations of these techniques. We also discuss the current understanding in cytocompatibility and biocompatibility issues related to graphene formulations and their implications pertinent to clinical cancer management. PMID:26769305

PARALLEL MODELS OF ASSESSMENT: INFANT MENTAL HEALTH AND THERAPEUTIC ASSESSMENT MODELS INTERSECT THROUGH EARLY CHILDHOOD CASE STUDIES.

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Gart, Natalie; Zamora, Irina; Williams, Marian E

2016-07-01

Therapeutic Assessment (TA; S.E. Finn & M.E. Tonsager, 1997; J.D. Smith, 2010) is a collaborative, semistructured model that encourages self-discovery and meaning-making through the use of assessment as an intervention approach. This model shares core strategies with infant mental health assessment, including close collaboration with parents and caregivers, active participation of the family, a focus on developing new family stories and increasing parents' understanding of their child, and reducing isolation and increasing hope through the assessment process. The intersection of these two theoretical approaches is explored, using case studies of three infants/young children and their families to illustrate the application of TA to infant mental health. The case of an 18-month-old girl whose parents fear that she has bipolar disorder illustrates the core principles of the TA model, highlighting the use of assessment intervention sessions and the clinical approach to preparing assessment feedback. The second case follows an infant with a rare genetic syndrome from ages 2 to 24 months, focusing on the assessor-parent relationship and the importance of a developmental perspective. Finally, assessment of a 3-year-old boy illustrates the development and use of a fable as a tool to provide feedback to a young child about assessment findings and recommendations. © 2016 Michigan Association for Infant Mental Health.

On the Toxicity of Therapeutically Used Nanoparticles: An Overview

International Nuclear Information System (INIS)

El-Ansary, A.; Al-Daihan, S.

2009-01-01

Human beings have been exposed to airborne nano sized particles throughout their evolutionary stages, and such exposures have increased dramatically over the last century. The rapidly developing field of nano technology will result in new sources of this exposure, through inhalation, ingestion, and injection. Although nano materials are currently being widely used in modern technology, there is a serious lack of information concerning the human health and environmental implications of manufactured nano materials. Since these are relatively new particles, it is necessary to investigate their toxicological behavior. The objective of this review was to trace the cellular response to nano sized particle exposure. Therapeutic application of selected nanoparticles together with their range of toxic doses was also reviewed. Effect of therapeutically used nanoparticles on cell membrane, mitochondrial function, pro oxidant/antioxidant status, enzyme leakage, DNA, and other biochemical endpoints was elucidated. This paper highlights the need for caution during the use and disposal of such manufactured nano materials to prevent unintended environmental impacts.

On the Toxicity of Therapeutically Used Nanoparticles: An Overview

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A. El-Ansary

2009-01-01

Full Text Available Human beings have been exposed to airborne nanosized particles throughout their evolutionary stages, and such exposures have increased dramatically over the last century. The rapidly developing field of nanotechnology will result in new sources of this exposure, through inhalation, ingestion, and injection. Although nanomaterials are currently being widely used in modern technology, there is a serious lack of information concerning the human health and environmental implications of manufactured nanomaterials. Since these are relatively new particles, it is necessary to investigate their toxicological behavior. The objective of this review was to trace the cellular response to nanosized particle exposure. Therapeutic application of selected nanoparticles together with their range of toxic doses was also reviewed. Effect of therapeutically used nanoparticles on cell membrane, mitochondrial function, prooxidant/antioxidant status, enzyme leakage, DNA, and other biochemical endpoints was elucidated. This paper highlights the need for caution during the use and disposal of such manufactured nanomaterials to prevent unintended environmental impacts.

Epigenetic developmental programs and adipogenesis: implications for psychotropic induced obesity.

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Chase, Kayla; Sharma, Rajiv P

2013-11-01

Psychotropic agents are notorious for their ability to increase fat mass in psychiatric patients. The two determinants of fat mass are the production of newly differentiated adipocytes (adipogenesis), and the volume of lipid accumulation. Epigenetic programs have a prominent role in cell fate commitments and differentiation required for adipogenesis. In parallel, epigenetic effects on energy metabolism are well supported by several genetic models. Consequently, a variety of psychotropics, often prescribed in combinations and for long periods, may utilize a common epigenetic effector path causing an increase in adipogenesis or reduction in energy metabolism. In particular, the recent discovery that G protein coupled signaling cascades can directly modify epigenetic regulatory enzymes implicates surface receptor activity by psychotropic medications. The potential therapeutic implications are also suggested by the effects of the clinically approved antidepressant tranylcypromine, also a histone demethylase inhibitor, which has impressive therapeutic effects on metabolism in the obese phenotype.

Recent concepts concerning cerebral ischaemia in man and their implications in therapeutic evaluations

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Depresseux, J C

1987-06-18

Recent concepts concerning focal cerebral ischaemia in man and resulting from the data obtained with positron emission tomography are reported. The evolutive steps in the ischaemic process are divided into: perfusion reserve; extraction reserve recruitment; ischaemic penumbra; lesional process and post-lesional developments. Circulatory and metabolic patterns corresponding to these evolutive steps are described and illustrated. The potentials of these data as guide-lines in therapeutic trial methodology are discussed.

Recent concepts concerning cerebral ischaemia in man and their implications in therapeutic evaluations

International Nuclear Information System (INIS)

Depresseux, J.C.

1987-01-01

Recent concepts concerning focal cerebral ischaemia in man and resulting from the data obtained with positron emission tomography are reported. The evolutive steps in the ischaemic process are divided into: perfusion reserve; extraction reserve recruitment; ischaemic penumbra; lesional process and post-lesional developments. Circulatory and metabolic patterns corresponding to these evolutive steps are described and illustrated. The potentials of these data as guide-lines in therapeutic trial methodology are discussed [fr

Therapeutic Perspectives of 8-Prenylnaringenin, a Potent Phytoestrogen from Hops

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Kateřina Štulíková

2018-03-01

Full Text Available Hop (Humulus lupulus L., as a key ingredient for beer brewing, is also a source of many biologically active molecules. A notable compound, 8-prenylnaringenin (8-PN, structurally belonging to the group of prenylated flavonoids, was shown to be a potent phytoestrogen, and thus, became the topic of active research. Here, we overview the pharmacological properties of 8-PN and its therapeutic opportunities. Due to its estrogenic effects, administration of 8-PN represents a novel therapeutic approach to the treatment of menopausal and post-menopausal symptoms that occur as a consequence of a progressive decline in hormone levels in women. Application of 8-PN in the treatment of menopause has been clinically examined with promising results. Other activities that have already been assessed include the potential to prevent bone-resorption or inhibition of tumor growth. On the other hand, the use of phytoestrogens is frequently questioned regarding possible adverse effects associated with long-term consumption. In conclusion, we emphasize the implications of using 8-PN in future treatments of menopausal and post-menopausal symptoms, including the need for precise evidence and further investigations to define the safety risks related to its therapeutic use.

Recovering Process from Child Sexual Abuse During Adulthood from an Integrative Approach to Solution-Focused Therapy: A Case Study.

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Gonzalez, Carolina

2017-10-01

In recent times, strengths-based recovery approaches that focus on the present and build strategies that look toward the future have become popular. However, some cases require the consideration of experiences from previous stages of the clients' development. This single-case study explores the psychotherapeutic process of a middle-aged woman who presented with a history of child sexual abuse (incest) and a long-term adult diagnosis of depression that was treated in public health services. This psychotherapy involved an integrative approach to solution-focused therapy; specifically, the approach proposed by Yvonne Dolan to work with adult survivors of sexual abuse, in conjunction with techniques and strategies from the transtheoretical model. Measures incorporating therapeutic working alliance and outcomes were administered over sessions. Results showed positive outcomes from this therapeutic intervention, which remained at 3-month and 12-month follow-ups. Implications for practitioners' specialist practice in health services are discussed, given the complexity of comorbid mental health conditions with a history of child sexual abuse.

Realizing the therapeutic potential of rare earth elements in designing nanoparticles to target and treat glioblastoma.

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Lu, Victor M; McDonald, Kerrie L; Townley, Helen E

2017-10-01

The prognosis of brain cancer glioblastoma (GBM) is poor, and despite intense research, there have been no significant improvements within the last decade. This stasis implicates the need for more novel therapeutic investigation. One such option is the use of nanoparticles (NPs), which can be beneficial due to their ability to penetrate the brain, overcome the blood-brain barrier and take advantage of the enhanced permeation and retention effect of GBM to improve specificity. Rare earth elements possess a number of interesting natural properties due to their unique electronic configuration, which may prove therapeutically advantageous in an NP formulation. The underexplored exciting potential for rare earth elements to augment the therapeutic potential of NPs in GBM treatment is discussed in this review.

Vaginal and bladder angiosarcoma after therapeutic irradiation

International Nuclear Information System (INIS)

Morgan, M.A.; Moutos, D.M.; Pippitt, C.H. Jr.; Suda, R.R.; Smith, J.J.; Thurnau, G.R.

1989-01-01

Angiosarcoma involving the female genitourinary tract is a rare soft tissue malignancy of vascular origin. We have described probably the first reported case of postirradiation angiosarcoma involving the vagina and bladder, and have reviewed the existing literature on the subject of angiosarcoma resulting from previous therapeutic irradiation for gynecologic malignancy.10 references

Maternally Sequestered Therapeutic Polypeptides – A New Approach for the Management of Preeclampsia

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Eric eGeorge

2014-09-01

Full Text Available The last several decades have seen intensive research into the molecular mechanisms underlying the symptoms of preeclampsia. While the underlying cause of preeclampsia is believed to be defective placental development and resulting placental ischemia, it is only recently that the links between the ischemic placenta and maternal symptomatic manifestation have been elucidated. Several different pathways have been implicated in the development of the disorder; most notably production of the anti-angiogenic protein sFlt-1, induction of auto-immunity and inflammation, and production of reactive oxygen species. While the molecular mechanisms are becoming clearer, translating that knowledge into effective therapeutics has proven elusive. Here we describe a number of peptide based therapies we have developed to target theses pathways, and which are currently being tested in preclinical models. These therapeutics are based on a synthetic polymeric carrier elastin-like polypeptide (ELP, which can be synthesized in various sequences and sizes to stabilize the therapeutic peptide and avoid crossing the placental interface. This prevents fetal exposure and potential developmental effects. The therapeutics designed will target known pathogenic pathways, and the ELP carrier could prove to be a versatile delivery system for administration of a variety of therapeutics during pregnancy.

The Complex Relationship between Antipsychotic-Induced Weight Gain and Therapeutic Benefits: A Systematic Review and Implications for Treatment

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Alex T. Raben

2018-01-01

Full Text Available Background: Antipsychotic-induced weight gain (AIWG and other adverse metabolic effects represent serious side effects faced by many patients with psychosis that can lead to numerous comorbidities and which reduce the lifespan. While the pathophysiology of AIWG remains poorly understood, numerous studies have reported a positive association between AIWG and the therapeutic benefit of antipsychotic medications.Objectives: To review the literature to (1 determine if AIWG is consistently associated with therapeutic benefit and (2 investigate which variables may mediate such an association.Data Sources: MEDLINE, Google Scholar, Cochrane Database and PsycINFO databases were searched for articles containing all the following exploded MESH terms: schizophrenia [AND] antipsychotic agents/neuroleptics [AND] (weight gain [OR] lipids [OR] insulin [OR] leptin [AND] treatment outcome. Results were limited to full-text, English journal articles.Results: Our literature search uncovered 31 independent studies which investigated an AIWG-therapeutic benefit association with a total of 6063 enrolled individuals diagnosed with schizophrenia or another serious mental illness receiving antipsychotic medications. Twenty-two studies found a positive association while, 10 studies found no association and one study reported a negative association. Study variables including medication compliance, sex, ethnicity, or prior antipsychotic exposure did not appear to consistently affect the AIWG-therapeutic benefit relationship. In contrast, there was some evidence that controlling for baseline BMI/psychopathology, duration of treatment and specific agent studied [i.e., olanzapine (OLZ or clozapine (CLZ] strengthened the relationship between AIWG and therapeutic benefit.Limitations: There were limitations of the reviewed studies in that many had small sample sizes, and/or were retrospective. The heterogeneity of the studies also made comparisons difficult and publication bias

[Gut microbiota: Description, role and pathophysiologic implications].

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Landman, C; Quévrain, E

2016-06-01

The human gut contains 10(14) bacteria and many other micro-organisms such as Archaea, viruses and fungi. Studying the gut microbiota showed how this entity participates to gut physiology and beyond this to human health, as a real "hidden organ". In this review, we aimed to bring information about gut microbiota, its structure, its roles and its implication in human pathology. After bacterial colonization in infant, intestinal microbial composition is unique for each individual although more than 95% can be assigned to four major phyla. The use of culture independent methods and more recently the development of high throughput sequencing allowed to depict precisely gut microbiota structure and diversity as well as its alteration in diseases. Gut microbiota is implicated in the maturation of the host immune system and in many fundamental metabolic pathways including sugars and proteins fermentation and metabolism of bile acids and xenobiotics. Imbalance of gut microbial populations or dysbiosis has important functional consequences and is implicated in many digestive diseases (inflammatory bowel diseases, colorectal cancer, etc.) but also in obesity and autism. These observations have led to a surge of studies exploring therapeutics which aims to restore gut microbiota equilibrium such as probiotics or fecal microbiota transplantation. But recent research also investigates biological activity of microbial products which could lead to interesting therapeutics leads. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Sphingosine 1-phosphate (S1P) signalling: Role in bone biology and potential therapeutic target for bone repair.

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Sartawi, Ziad; Schipani, Ernestina; Ryan, Katie B; Waeber, Christian

2017-11-01

The lipid mediator sphingosine 1-phosphate (S1P) affects cellular functions in most systems. Interest in its therapeutic potential has increased following the discovery of its G protein-coupled receptors and the recent availability of agents that can be safely administered in humans. Although the role of S1P in bone biology has been the focus of much less research than its role in the nervous, cardiovascular and immune systems, it is becoming clear that this lipid influences many of the functions, pathways and cell types that play a key role in bone maintenance and repair. Indeed, S1P is implicated in many osteogenesis-related processes including stem cell recruitment and subsequent differentiation, differentiation and survival of osteoblasts, and coupling of the latter cell type with osteoclasts. In addition, S1P's role in promoting angiogenesis is well-established. The pleiotropic effects of S1P on bone and blood vessels have significant potential therapeutic implications, as current therapeutic approaches for critical bone defects show significant limitations. Because of the complex effects of S1P on bone, the pharmacology of S1P-like agents and their physico-chemical properties, it is likely that therapeutic delivery of S1P agents will offer significant advantages compared to larger molecular weight factors. Hence, it is important to explore novel methods of utilizing S1P agents therapeutically, and improve our understanding of how S1P and its receptors modulate bone physiology and repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hepatic leukemia factor promotes resistance to cell death: Implications for therapeutics and chronotherapy

International Nuclear Information System (INIS)

Waters, Katrina M.; Sontag, Ryan L.; Weber, Thomas J.

2013-01-01

Physiological variation related to circadian rhythms and aberrant gene expression patterns are believed to modulate therapeutic efficacy, but the precise molecular determinants remain unclear. Here we examine the regulation of cell death by hepatic leukemia factor (HLF), which is an output regulator of circadian rhythms and is aberrantly expressed in human cancers, using an ectopic expression strategy in JB6 mouse epidermal cells and human keratinocytes. Ectopic HLF expression inhibited cell death in both JB6 cells and human keratinocytes, as induced by serum-starvation, tumor necrosis factor alpha and ionizing radiation. Microarray analysis indicates that HLF regulates a complex multi-gene transcriptional program encompassing upregulation of anti-apoptotic genes, downregulation of pro-apoptotic genes, and many additional changes that are consistent with an anti-death program. Collectively, our results demonstrate that ectopic expression of HLF, an established transcription factor that cycles with circadian rhythms, can recapitulate many features associated with circadian-dependent physiological variation. - Highlights: ► Circadian-dependent physiological variation impacts therapeutic efficacy. ► Hepatic leukemia factor inhibits cell death and is a candidate circadian factor. ► Hepatic leukemia factor anti-death program is conserved in murine and human cells. ► Transcriptomics indicates the anti-death program results from a systems response

Hepatic leukemia factor promotes resistance to cell death: Implications for therapeutics and chronotherapy

Energy Technology Data Exchange (ETDEWEB)

Waters, Katrina M. [Computational Biology and Bioinformatics, Pacific Northwest National Laboratory, Richland, WA 99354 (United States); Sontag, Ryan L. [Systems Toxicology Groups, Pacific Northwest National Laboratory, Richland, WA 99354 (United States); Weber, Thomas J., E-mail: Thomas.Weber@pnl.gov [Systems Toxicology Groups, Pacific Northwest National Laboratory, Richland, WA 99354 (United States)

2013-04-15

Physiological variation related to circadian rhythms and aberrant gene expression patterns are believed to modulate therapeutic efficacy, but the precise molecular determinants remain unclear. Here we examine the regulation of cell death by hepatic leukemia factor (HLF), which is an output regulator of circadian rhythms and is aberrantly expressed in human cancers, using an ectopic expression strategy in JB6 mouse epidermal cells and human keratinocytes. Ectopic HLF expression inhibited cell death in both JB6 cells and human keratinocytes, as induced by serum-starvation, tumor necrosis factor alpha and ionizing radiation. Microarray analysis indicates that HLF regulates a complex multi-gene transcriptional program encompassing upregulation of anti-apoptotic genes, downregulation of pro-apoptotic genes, and many additional changes that are consistent with an anti-death program. Collectively, our results demonstrate that ectopic expression of HLF, an established transcription factor that cycles with circadian rhythms, can recapitulate many features associated with circadian-dependent physiological variation. - Highlights: ► Circadian-dependent physiological variation impacts therapeutic efficacy. ► Hepatic leukemia factor inhibits cell death and is a candidate circadian factor. ► Hepatic leukemia factor anti-death program is conserved in murine and human cells. ► Transcriptomics indicates the anti-death program results from a systems response.

Integrins as Therapeutic Targets: Successes and Cancers

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Sabine Raab-Westphal

2017-08-01

Full Text Available Integrins are transmembrane receptors that are central to the biology of many human pathologies. Classically mediating cell-extracellular matrix and cell-cell interaction, and with an emerging role as local activators of TGFβ, they influence cancer, fibrosis, thrombosis and inflammation. Their ligand binding and some regulatory sites are extracellular and sensitive to pharmacological intervention, as proven by the clinical success of seven drugs targeting them. The six drugs on the market in 2016 generated revenues of some US$3.5 billion, mainly from inhibitors of α4-series integrins. In this review we examine the current developments in integrin therapeutics, especially in cancer, and comment on the health economic implications of these developments.

Immunogenicity of therapeutic proteins. Part 2: impact of container closures.

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Sharma, Basant

2007-01-01

Immunogenicity as a potential consequence of therapeutic protein administration is increasingly being scrutinized in the biopharmaceuticals industry, particularly with the imminent introduction of biosimilar products. Immunogenicity is an important safety aspect requiring rigorous investigation to fully appreciate its impact. Factors involved in product handling, such as storage temperature, light exposure, and shaking, have been implicated in immunogenicity, while container closure systems are no less important. Intended to provide a stable environment for the dosage form, container closures may also interact with a product, affecting performance and potentially enhancing immunogenicity. Glass surfaces, air-liquid interfaces, and lubricants can mediate protein denaturation, while phthalates in plastics and latex rubber are sources of extractables and leachates that may contaminate a product, causing allergic reactions and increasing immunogenicity. The manufacture of therapeutic proteins therefore requires rigorous safety evaluations not just in the context of the product, but also product containment.

Therapeutic antibodies as a treatment option for dengue fever.

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Chan, Kuan Rong; Ong, Eugenia Z; Ooi, Eng Eong

2013-11-01

Dengue fever is the most prevalent mosquito-borne viral disease globally with about 100 million cases of acute dengue annually. Severe dengue infection can result in a life-threatening illness. In the absence of either a licensed vaccine or antiviral drug against dengue, therapeutic antibodies that neutralize dengue virus (DENV) may serve as an effective medical countermeasure against severe dengue. However, therapeutic antibodies would need to effectively neutralize all four DENV serotypes. It must not induce antibody-dependent enhancement of DENV infection in monocytes/macrophages through Fc gamma receptor (FcγR)-mediated phagocytosis, which is hypothesized to increase the risk of severe dengue. Here, we review the strategies and technologies that can be adopted to develop antibodies for therapeutic applications. We also discuss the mechanism of antibody neutralization in the cells targeted by DENV that express Fc gamma receptor. These studies have provided significant insight toward the use of therapeutic antibodies as a potentially promising bulwark against dengue.

Companion animal welfare and possible implications on the human-pet relationship

OpenAIRE

Marina Verga; Manuela Michelazzi

2010-01-01

The role of pets (dogs and cats in particular) in human society has changed in recent years. Nowadays pets are an integral part of the human family and this aspect has many social and emotional implications. For their positive effects on human health, pets are also employed in some special and therapeutic activities known by the generic term of “Pet Therapy”. In these programmes the animal becomes an integral part of the therapeutic plan in order to induce some physical, social, e...

Therapeutic Assessment in Psychological Triage Using the PAI.

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Brown, Joshua D; Morey, Leslie C

2016-01-01

This case illustrates the utility of incorporating therapeutic assessment in a triage context that typically involves a focus on gathering information. A man referred to our clinic by a local mental health center was seen by our assessment team for a triage that includes the administration of a single psychological test, the Personality Assessment Inventory (PAI). Although this triage must rapidly gather information to determine client suitability and treatment assignment, we still attempt to work with clients to collaboratively develop goals for this assessment that include addressing questions that are central concerns for the clients. In this case, the test results suggested a severe disorder that accounted for many phenomena that he had been experiencing but had apparently been reluctant to share. The information gathered led to a referral to a different treatment program that could provide pharmacological and more intensive forms of treatment. However, the collaborative bond formed between the assessor and the client during this triage was sufficiently strong that it was our assessor to whom the client turned in a subsequent crisis precipitated by a symptomatic exacerbation. This case illustrates complementary information gathering and therapeutic goals of assessment even in the context of a brief assessment.

Poisons Implicated In Homicidal, Suicidal And Accidental Cases In North-West Pakistan.

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Jan, Adil; Khan, Muhammad Jaffar; Humayun Khan, Muhammad Tariq; Masood Khan, Muhammad Tariq; Fatima, Sadia

2016-01-01

Pakistan has one of the highest prevalence of poisoning in the world. However, limited data exist on the frequency of poisons implicated in homicidal, suicidal, and accidental cases in North-West Pakistan (Khyber Pakhtunkhwa). This retrospective study of 353 cases and biological specimens of poisoning received at the department of Forensic medicine and toxicology, Khyber Medical College Peshawar from 13 districts of Khyber Pakhtunkhwa. Frequency of poisoning was assessed by testing each specimen for 17 different poisons. Of all the specimens, 250 (70.8%) specimens tested positive and the rest didn't show any indication of poisoning (n=103, 29.2%). The most frequent poisons detected were benzodiazepines (total n=75), organophosphates (total n=58), phencyclidine (total n=30) and morphine (total n=23). Gender had a significant association with benzodiazepines (p=0.011), tricyclic antidepressants (p=0.001), and organophosphates (ppoisoning in females while benzodiazepines were the most common cause of poisoning in males. Poisoning by benzodiazepines, organophosphates and phencyclidine are the most common causes of intoxication in population of Khyber Pakhtunkhwa. Source of poisoning varies with gender for organophosphates, benzodiazepines and tricyclic antidepressants.

Angiotensin receptor blockers & endothelial dysfunction: Possible correlation & therapeutic implications

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Miroslav Radenkovic

2016-01-01

Full Text Available The endothelium is one of the most important constituents of vascular homeostasis, which is achieved through continual and balanced production of different relaxing and contractile factors. When there is a pathological disturbance in release of these products, endothelial dysfunction (ED will probably occur. ED is considered to be the initial step in the development of atherosclerosis. This pathological activation and inadequate functioning of endothelial cells was shown to be to some extent a reversible process, which all together resulted in increased interest in investigation of different beneficial treatment options. To this point, the pharmacological approach, including for example, the use of angiotensin-converting enzyme inhibitors or statins, was clearly shown to be effective in the improvement of ED. One of many critical issues underlying ED represents instability in the balance between nitric oxide and angiotensin II (Ang II production. Considering that Ang II was confirmed to be important for the development of ED, the aim of this review article was to summarize the findings of up to date clinical studies associated with therapeutic application of angiotensin receptor blockers and improvement in ED. In addition, it was of interest to review the pleiotropic actions of angiotensin receptor blockers linked to the improvement of ED. The prospective, randomized, double-blind, placebo or active-controlled clinical trials were identified and selected for the final evaluation.

Umbilical melanoma: case report and review of anatomical and therapeutic aspects

International Nuclear Information System (INIS)

Brandao, Eduardo Miranda; Gomes, Alexandre Santos de Almeida; Ribeiro, Edilana Sa; Vilaca, Thiago Guimaraes; Macedo, Francisco Igor Bulcao de; Santos, Rogerio Luiz dos; Pernambuco Univ., Recife, PE

2005-01-01

Full text of publication follows: Background: Malignant melanoma corresponds to 5% of cutaneous neoplasias. However, umbilical melanoma is a rare occurrence, with only 13 cases reported on the literature. The purpose of this article is to present a case of umbilical primary melanoma, discuss the anatomy and lymphatic drainage of this region, and the therapeutic aspects. Clinical description: Three years ago, a 65 years-old white woman from Recife-PE, presented an umbilical pigmented nevus. It grew in size and one year ago the pigmentation increased. Examination showed depressed umbilical scarring completely filled by pigmented lesion with 1.5 cm, irregular borders and a depigmented area; no enlarged inguinal and axillary lymph nodes. Chest X-Ray, CT scan of abdomen and pelvis, and ultrasonography of groin and axillary lymphatic chains were normal. The pathological diagnosis after incisional biopsy was ulcerated malignant melanoma, without defining Breslow classification. Subsequently a complete excision of the lesion was performed; slide showed Breslow 8 mm and 1 mm of margin. Lymphoscintillography showed three left axillary lymph nodes. During surgical widening, the peritoneum seemed disease-free. Lymphatic mapping identified three lymph nodes, one of them not coloured by vital blue. All the lymph nodes were free of metastasis on histopathological and immunohistochemical examination. Discussion: Among the umbilical tumors, 80% are metastatic, the most common branch of which is the gastrointestinal tract. Melanoma is included in the other 20% corresponding to primary neoplasias of the umbilicus, which also include sarcomas, basal cell carcinomas and squamous cell carcinomas. From the embryological point of view, the umbilical scar can contain residues of several types of epithelial tissue of the gastrointestinal duct remaining from the omphalomesenteric duct. Anatomical aspects remain to be studied, such as the cylindrical form and the content within its thickness

Epistemological beliefs and therapeutic health concepts of physiotherapy students and professionals.

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Bientzle, Martina; Cress, Ulrike; Kimmerle, Joachim

2014-10-01

Health knowledge develops fast and includes a lot of ambiguous or tentative information. In their daily routine, both health care students and professionals continuously have to make judgments about the viability of health knowledge. People's epistemological beliefs (EBs) and their therapeutic health concepts are factors that influence how they deal with health knowledge. However, very little is known about the occurrence of these factors at different stages of people's career. The present study examines the EBs and therapeutic health concepts of physiotherapy students in their vocational training and the EBs and therapeutic health concepts of professionals. In a cross-sectional study physiotherapy students and professional physiotherapists filled in a questionnaire that measured their personal EBs about physiotherapy and medicine, as well as their biomedical and biopsychosocial therapeutic health concepts. We compared the participants' EBs regarding both knowledge domains, and their therapeutic health concepts using paired samples t-tests. We also examined the differences between first-year students, advanced students, and professionals regarding their EBs and their therapeutic health concepts using ANOVAs. Eighty-three students and 84 professionals participated in this study, 114/167 (68%) participants were female. EBs as well as therapeutic health concepts differed depending upon the participants' training status. Professionals had more sophisticated EBs than students regarding both knowledge in physiotherapy (F(2, 164) = 6.74, P = 0.002, η(2)(p) = 0.08) and knowledge in medicine (F(2, 164) = 5.93, P = 0.003, η(2)(p) = 0.07). In addition, high values in a biopsychosocial therapeutic health concept already occurred in an early phase of training (F(2, 164) = 5.39, P = 0.005, η(2)(p) = 0.06), whereas increased values in a biomedical concept did not occur until people's professional life (F(2, 164) = 10.99, P students as

Therapeutic Assessment of Complex Trauma: A Single-Case Time-Series Study

OpenAIRE

Tarocchi, Anna; Aschieri, Filippo; Fantini, Francesca; Smith, Justin D.

2013-01-01

The cumulative effect of repeated traumatic experiences in early childhood incrementally increases the risk of adjustment problems later in life. Surviving traumatic environments can lead to the development of an interrelated constellation of emotional and interpersonal symptoms termed complex posttraumatic stress disorder (CPTSD). Effective treatment of trauma begins with a multimethod psychological assessment and requires the use of several evidence-based therapeutic processes, including es...

Therapeutic Dancing for Parkinson's Disease

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Lorenna Pryscia Carvalho Aguiar

2016-06-01

Full Text Available Therapeutic dancing has been advocated as an effective adjunct to conventional physical therapies for people living with Parkinson's disease (PD. This systematic review evaluates studies on the outcomes of different dance genres on mobility and quality of life in PD. We searched databases including CINHAL (1982–2015, Medline (1922–2015, Scopus (1996–2015, Web of Science (2002–2015, Embase (2007–2015, PEDro (1999–2015 and the Cochrane Library (1996–2015. The key words were: Parkinson's disease, Parkinson*, Parkinsonism, dance, dance therapy, dance genres, safety, feasibility, and quality of life. Two independent investigators reviewed the texts. Only randomized controlled trials, quasirandomized controlled trials, and case series studies were included. There was emerging evidence that therapeutic dance can be safe and feasible for people with mild to moderately severe PD, with beneficial effects on walking, freezing of gait, and health related quality of life.

Interviewing children in custody cases: implications of research and policy for practice.

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Saywitz, Karen; Camparo, Lorinda B; Romanoff, Anna

2010-01-01

Research on child interviewing has burgeoned over the past 25 years as expectations about children's agency, competence, and participation in society have changed. This article identifies recent trends in research, policy, and theory with implications for the practice of interviewing children in cases of contested divorce and for the weight to be given the information children provide. A number of fields of relevant research are identified, including studies of families who have participated in the family law system, studies of child witnesses in the field, experimental studies of the effects of interview techniques on children's memory and suggestibility, and ethnographic methods that elicit children's views of their own experiences. Finally, a set of 10 principles for practice are delineated based on the best available science. Copyright 2010 John Wiley & Sons, Ltd.

Medical nutrition therapy in chronic kidney disease; from dialysis to transplant: A case report

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Gabriela Leal-Escobar

2016-01-01

Full Text Available Chronic kidney disease has direct implications in nutritional status, causing anorexia and muscular catabolism. These situations are frequent in kidney renal replacement therapy in which nutritional disorders and inflammatory mechanisms associated with therapy often lead to the development of protein-energy wasting. Nutrition therapy has shown an adequate therapeutic strategy to prevent and treat metabolic alterations, reducing surgical and nutritional complication risks in kidney transplantation patients. The current case reports nutritional intervention on a continuous ambulatory peritoneal dialysis patient who was subsequently prescribed to automatic peritoneal dialysis and, finally, kidney transplant from a living donor.

The relationship between adult attachment style and therapeutic alliance in individual psychotherapy: a meta-analytic review.

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Diener, Marc J; Monroe, Joel M

2011-09-01

The present study examined the relationship between adult attachment style and therapeutic alliance in individual psychotherapy. Search procedures yielded 17 independent samples (total N = 886, average n = 52, standard deviation = 24) for inclusion in the meta-analysis. Results indicated that greater attachment security was associated with stronger therapeutic alliances, whereas greater attachment insecurity was associated with weaker therapeutic alliances, with an overall weighted effect size of r = .17, p .10) with the exception of the source of alliance ratings; results indicated that patient-rated alliance demonstrated a significantly larger relationship with attachment compared with therapist-rated alliance (Qbetween = 3.95, df = 1, p = .047). Implications for clinical practice and future research are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved). (c) 2011 APA, all rights reserved.

Four therapeutic cases of RS3PE syndrome

International Nuclear Information System (INIS)

Nakajima, Naoya; Fukuda, Yukiko; Yang, Kwang-Seok; Aiba, Miyoji; Tsuda, Hiroshi

2007-01-01

RS3PE syndrome (Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome) is one of the disorders which present as polyarthritis. It is important to be aware of RS3PE syndrome when encountering elderly patients with polyarthritis who are negative for rheumatoid factor. We report 4 cases of RS3PE syndrome. All cases shared common clinical findings, such as acute onset, symmetrical polyarthritis, pitting edema of the hands and feet, and being negative for rheumatoid factor in serum. Treatment with corticosteroid was very effective in all cases. However, two patients showed a deteriorated clinical condition during the tapering of corticosteroid. Corticosteroid should be tapered off cautiously in patients with RS3PE syndrome. (author)

Will Synergizing Vaccination with Therapeutics Boost Measles Virus Eradication?

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Plemper, Richard K; Hammond, Anthea L

2014-01-01

Introduction Measles virus is a major human pathogen responsible for approximately 150,000 measles deaths annually. The disease is vaccine preventable and eradication of the virus is considered feasible in principle. However, a herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population. Declining disease prevalence combined with public anxieties about vaccination safety has increased vaccine refusal especially in the European region, which has resulted in measles resurgence in some areas. Areas covered Here, we discuss whether synergizing effective measles therapeutics with vaccination could contribute to solving an endgame conundrum of measles elimination by accelerating the eradication effort. Based on an anticipated use for protection of high-risk contacts of confirmed measles cases through post-exposure prophylaxis, we identify key elements of the desirable drug profile, review current disease management strategies and the state of experimental inhibitor candidates, evaluate the risk associated with viral escape from inhibition, and consider the potential of measles therapeutics for the management of persistent viral infection of the CNS. Assuming a post-measles world with waning measles immunity, we contemplate the possible impact of therapeutics on controlling the threat imposed by closely related zoonotic pathogens of the same genus as measles virus. Expert opinion Efficacious therapeutics given for post-exposure prophylaxis of high-risk social contacts of confirmed index cases may aid measles eradication by closing herd immunity gaps due to vaccine refusal or failure in populations with overall good vaccination coverage. The envisioned primarily prophylactic application of measles therapeutics to a predominantly pediatric and/or adolescent patient population dictates the drug profile; the article must be safe and efficacious, orally available, shelf-stable at ambient temperature, and amenable to cost-effective manufacture

Crosstalk between Apoptosis and Autophagy: Molecular Mechanisms and Therapeutic Strategies in Cancer

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Abdelouahid El-Khattouti

2013-01-01

Full Text Available Both apoptosis and autophagy are highly conserved processes that besides their role in the maintenance of the organismal and cellular homeostasis serve as a main target of tumor therapeutics. Although their important roles in the modulation of tumor therapeutic strategies have been widely reported, the molecular actions of both apoptosis and autophagy are counteracted by cancer protective mechanisms. While apoptosis is a tightly regulated process that is implicated in the removal of damaged or unwanted cells, autophagy is a cellular catabolic pathway that is involved in lysosomal degradation and recycling of proteins and organelles, and thereby is considered an important survival/protective mechanism for cancer cells in response to metabolic stress or chemotherapy. Although the relationship between autophagy and cell death is very complicated and has not been characterized in detail, the molecular mechanisms that control this relationship are considered to be a relevant target for the development of a therapeutic strategy for tumor treatment. In this review, we focus on the molecular mechanisms of apoptosis, autophagy, and those of the crosstalk between apoptosis and autophagy in order to provide insight into the molecular mechanisms that may be essential for the balance between cell survival and death as well as their role as targets for the development of novel therapeutic approaches.

Trauma y trastornos de la alimentación: Implicaciones teóricas y terapéuticas Trauma and eating disorders: Theoretical and therapeutical implications

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Luisa Castaldi

2008-12-01

Full Text Available Los trastornos de alimentación representan un fenómeno complejo, cuya aproximación implica miradas que integren múltiples niveles de análisis. El presente documento pretende analizar el concepto de trauma relacional aplicado a contextos relacionales en los cuales un miembro presenta tal sintomatología. Se presentan y articulan las implicancias ligadas a la hipótesis planteada, con el objetivo de evidenciar como el tomar en consideración la existencia de un trauma relacional puede ser útil para profundizar aspectos de la dinámica familiar y del posicionamiento individual del miembro sintomático, integrando los aportes psicoanalíticos y sistémicos. Se articulará dicho concepto con la visión trigeneracional clásica y se explicitarán las implicancias posibles en relación al trabajo terapéutico. Eating disorders represent a complex phenomenon that requires a multiple-level analysis approach. The present document analyzes the concept of relational trauma applied to relational contexts where a member presents the symptomatology. The implications linked to the hypothesis proposed are presented and articulated, with the purpose of providing evidence of how considering the existence of a relational trauma can be useful for analyzing elements of family dynamics and of the individual positioning of the symptomatic member, integrating both psychoanalytic and systemic contributions. The concept of relational trauma is articulated with the traditional third-generation view, and the possible implications concerning therapeutic work are stated.

Therapeutic Jurisprudence in Health Research: Enlisting Legal Theory as a Methodological Guide in an Interdisciplinary Case Study of Mental Health and Criminal Law.

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Ferrazzi, Priscilla; Krupa, Terry

2015-09-01

Studies that seek to understand and improve health care systems benefit from qualitative methods that employ theory to add depth, complexity, and context to analysis. Theories used in health research typically emerge from social science, but these can be inadequate for studying complex health systems. Mental health rehabilitation programs for criminal courts are complicated by their integration within the criminal justice system and by their dual health-and-justice objectives. In a qualitative multiple case study exploring the potential for these mental health court programs in Arctic communities, we assess whether a legal theory, known as therapeutic jurisprudence, functions as a useful methodological theory. Therapeutic jurisprudence, recruited across discipline boundaries, succeeds in guiding our qualitative inquiry at the complex intersection of mental health care and criminal law by providing a framework foundation for directing the study's research questions and the related propositions that focus our analysis. © The Author(s) 2014.

Therapeutic implications of chemokine-mediated pathways in atherosclerosis: realistic perspectives and utopias.

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Apostolakis, Stavros; Amanatidou, Virginia; Spandidos, Demetrios A

2010-09-01

Current perspectives on the pathogenesis of atherosclerosis strongly support the involvement of inflammatory mediators in the establishment and progression of atherosclerostic lesions. Chemokine-mediated mechanisms are potent regulators of such processes by orchestrating the interactions of inflammatory cellular components of the peripheral blood with cellular components of the arterial wall. The increasing evidence supporting the role of chemokine pathways in atherosclerosis renders chemokine ligands and their receptors potential therapeutic targets. In the following review, we aim to highlight the special structural and functional features of chemokines and their receptors in respect to their roles in atherosclerosis, and examine to what extent available data can be applied in disease management practices.

Implications of microRNAs in Colorectal Cancer Development, Diagnosis, Prognosis and Therapeutics

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Haiyan eZhai

2011-11-01

Full Text Available MicroRNAs (miRNAs are a class of non-coding small RNAs with critical regulatory functions as post-transcriptional regulators. Due to the fundamental importance and broad impact of miRNAs on multiple genes and pathways, dysregulated miRNAs have been associated with human diseases, including cancer. Colorectal cancer (CRC is among the most deadly diseases, and miRNAs offer a new frontier for target discovery and novel biomarkers for both diagnosis and prognosis. In this review, we summarize the recent advancement of miRNA research in CRC, in particular, the roles of miRNAs in colorectal cancer stem cells, EMT, chemoresistance, therapeutics, diagnosis and prognosis.

The therapeutic role of the dacryocystography in patients with epiphora: three cases report; O papel terapeutico da dacriocistografia em pacientes com epifora: relato de tres casos

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Francisco, Fabiano Celli [Hospital de Caridade Sao Braz, Porto Uniao, SC (Brazil); Carvalho, Antonio Carlos Pires [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Faculdade de Medicina. Dept. de Radiologia; Francisco, Vivian Frida Murta; Mendonca Junior, Adhemar [Clinica Radiologica Emilio Amorim, Rio de Janeiro, RJ (Brazil); Torres Neto, Gilberto [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Faculdade de Ciencias Medicas. Disciplina de Radiologia; Francisco, Marina Celli [Universidade Evangelica do Parana (Brazil). Curso de Medicina

2006-10-15

We describe three cases of patients that presented epiphora having been submitted the accomplishment of dacryocystographic study, which ones turned asymptomatic after the accomplishment of the exam, without any other procedure or medicine. The therapeutic potential of the method is stood out, once the literature on this subject is scarce in children and none in adults. (author)

Molecular Pathology of Anaplastic Thyroid Carcinomas: A Retrospective Study of 144 Cases.

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Bonhomme, Benjamin; Godbert, Yann; Perot, Gaelle; Al Ghuzlan, Abir; Bardet, Stéphane; Belleannée, Geneviève; Crinière, Lise; Do Cao, Christine; Fouilloux, Geneviève; Guyetant, Serge; Kelly, Antony; Leboulleux, Sophie; Buffet, Camille; Leteurtre, Emmanuelle; Michels, Jean-Jacques; Tissier, Frédérique; Toubert, Marie-Elisabeth; Wassef, Michel; Pinard, Clémence; Hostein, Isabelle; Soubeyran, Isabelle

2017-05-01

Anaplastic thyroid carcinoma (ATC) is a rare tumor, with poorly defined oncogenic molecular mechanisms and limited therapeutic options contributing to its poor prognosis. The aims of this retrospective study were to determine the frequency of anaplastic lymphoma kinase (ALK) translocations and to identify the mutational profile of ATC including TERT promoter mutations. One hundred and forty-four ATC cases were collected from 10 centers that are a part of the national French network for management of refractory thyroid tumors. Fluorescence in situ hybridization analysis for ALK rearrangement was performed on tissue microarrays. A panel of 50 genes using next-generation sequencing and TERT promoter mutations using Sanger sequencing were also screened. Fluorescence in situ hybridization was interpretable for 90 (62.5%) cases. One (1.1%) case was positive for an ALK rearrangement with a borderline threshold (15% positive cells). Next-generation sequencing results were interpretable for 94 (65.3%) cases, and Sanger sequencing (TERT) for 98 (68.1%) cases. A total of 210 mutations (intronic and exonic) were identified. TP53 alterations were the most frequent (54.4%). Forty-three percent harbored a mutation in the (H-K-N)RAS genes, 13.8% a mutation in the BRAF gene (essentially p.V600E), 17% a PI3K-AKT pathway mutation, 6.4% both RAS and PI3K pathway mutations, and 4.3% both TP53 and PTEN mutations. Nearly 10% of the cases showed no mutations of the RAS, PI3K-AKT pathways, or TP53, with mutations of ALK, ATM, APC, CDKN2A, ERBB2, RET, or SMAD4, including mutations not yet described in thyroid tumors. Genes encoding potentially druggable targets included: mutations in the ATM gene in four (4.3%) cases, in ERBB2 in one (1.1%) case, in MET in one (1.1%) case, and in ALK in one (1.1%) case. A TERT promoter alteration was found in 53 (54.0%) cases, including 43 C228T and 10 C250T mutations. Three out of our cases did not harbor mutations in the panel of genes with therapeutic

Q fever in the Greek Island of Crete: epidemiologic, clinical, and therapeutic data from 98 cases.

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Tselentis, Y; Gikas, A; Kofteridis, D; Kyriakakis, E; Lydataki, N; Bouros, D; Tsaparas, N

1995-05-01

A retrospective study was undertaken in Crete, Greece, to investigate the epidemiologic, clinical, and therapeutic aspects of Q fever. Over a period of 5 years (1989-1993), 1,298 patients were examined and 98 cases were identified. Individuals who were aged 20-29 years and 30-39 years appeared to have an increased risk of infection. Contact with animals was found to be a major risk factor for acquisition of Q fever. The predominant clinical manifestations of the infection were fever (91.7% of patients) and respiratory disease (88.5%), whereas hepatitis was the dominant feature in only a minority (7.1%) of patients. Chest radiographs frequently revealed pulmonary interstitial changes (36.4% of patients) and alveolar changes (34.4%). Abnormal echocardiographic findings were also observed. There was no difference in the duration of fever whether the patient received therapy with tetracycline or erythromycin, a finding that may be explained by the delay in initiating tetracycline therapy.

Use of informed consent with therapeutic paradox.

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Farkas, M M

1992-01-01

Debate persists in the literature and among clinicians about the ethical appropriateness of paradoxical interventions. It has been suggested that informed consent with therapeutic paradox would alleviate ethical concerns of deception, manipulation, harm to the client, and withholding of information from the client in therapy. The purpose of this study was to explore health care consumer reactions to the benefits and risks of therapeutic paradox as stated in a consent for treatment form. The study explored the responses of 32 medical patients to a hypothetical consent for treatment form for therapeutic paradox. Data were collected in a brief semistructured interview after subjects read the hypothetical consent form. Utilizing a case study, the investigator then offered an example of a successful paradoxical intervention and additional subject comments were solicited. Content analysis of the responses was made. Health care consumers had mixed responses to the consent form. While the consent form served as an obstacle for some consumers, many were willing to sign the consent form and accept treatment even though they had internal reservations and questions. Appropriateness of the consent form format is discussed.

[Limitation of the therapeutic effort].

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Herreros, B; Palacios, G; Pacho, E

2012-03-01

The limitation of the therapeutic effort (LTE) consists in not applying extraordinary or disproportionate measures for therapeutic purposes that are proposed for a patient with poor life prognosis and/or poor quality of life. There are two types. The first is to not initiate certain measures or to withdraw them when they are established. A decision of the LTE should be based on some rigorous criteria, so that we make the following proposal. First, it is necessary to know the most relevant details of the case to make a decision: the preferences of the patient, the preferences of the family when pertinent, the prognosis (severity), the quality of life and distribution of the limited resources. After, the decision should be made. In this phase, participatory deliberation should be established to clarify the end of the intervention. Finally, if it is decided to perform an LTE, it should be decided how to do it. Special procedures, disproportionate measures, that are useless and vain should not be initiated for the therapeutic objective designed (withdraw them if they have been established). When it has been decided to treat a condition (interim measures), the treatment should be maintained. This complex phase may need stratification of he measures. Finally, the necessary palliative measures should be established. Copyright © 2011 Elsevier España, S.L. All rights reserved.

Development of a compassion-focused and contextual behavioural environment and validation of the Therapeutic Environment Scales (TESS).

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Veale, David; Miles, Sarah; Naismith, Iona; Pieta, Maria; Gilbert, Paul

2016-02-01

Aims and method The aims of the study were to develop a scale sensitive enough to measure the interpersonal processes within a therapeutic environment, and to explore whether the new scale was sensitive enough to detect differences between settings, including a community based on compassionate mind and contextual behaviourism. The Therapeutic Environment Scales (TESS) were validated with 81 participants in three different settings: a specialist service for anxiety disorders, a specialist in-patient ward and a psychodynamic therapeutic community. Results TESS was found to be reliable and valid. Significant differences were seen between the services on the dimensions of compassion, belongingness, feeling safe, positive reinforcement of members' acts of courage, extinction and accommodation of unhelpful behaviours, inconsistency and high expressed emotion. These processes were over time associated with improved outcomes on a specialist service for anxiety disorders. Clinical implications The TESS offers a first step in exploring important interpersonal relationships in therapeutic environments and communities. An environment based on a compassionate mind and contextual behaviourism offers promise for the running of a therapeutic community.

IGF system targeted therapy: Therapeutic opportunities for ovarian cancer.

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Liefers-Visser, J A L; Meijering, R A M; Reyners, A K L; van der Zee, A G J; de Jong, S

2017-11-01

The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Pemphigus in North-Western Yemen: A therapeutic study of 75 cases.

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Khatri, Mishri Lal

2016-01-01

The incidence of pemphigus, though not documented, seems to be quite high in Yemen. There is no universal consensus on the treatment of this disease. The aim was to evaluate the efficacy and side effects of different therapeutic regimens used in patients of pemphigus in North-Western Yemen. Seventy-five Yemeni patients (39 males and 36 females) were included. Diagnosis was based on clinical features, histopathology and the Tzanck test. Results of treatment with these different therapeutic regimens were compared: (1) dexamethasone-cyclophosphamide pulse (DCP), (2) dexamethasone pulse with oral azathioprine, (3) oral prednisolone with azathioprine, (4) oral prednisolone with oral cyclophosphamide, and (5) prednisolone monotherapy. Pemphigus vulgaris (PV) was diagnosed in 46 patients, pemphigus foliaceus (PF) in 23, pemphigus vegetans (PVEG) in 5 and pemphigus herpetiformis (PH) in one. Among the 16 patients who received regular DCP therapy, 13 were in remission for 6 months to 11 years without medications (phase 4). Remission without pharmacotherapy could not be achieved with the other regimens and steroid-induced side-effects appeared to be more than with DCP. Immunofluorescence was not available to confirm the diagnosis of pemphigus. Randomization was not done. The DCP regimen seemed to be superior to the other regimens used.

The role of expectation in the therapeutic outcomes of alcohol and drug addiction treatments.

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Spagnolo, Primavera A; Colloca, Luana; Heilig, Markus

2015-05-01

Throughout history, patient-physician relationships have been acknowledged as an important component of the therapeutic effects of any pharmacological treatment. Here, we discuss the role of physicians' expectations in influencing the therapeutic outcomes of alcohol and drug addiction pharmacological treatments. As largely demonstrated, such expectations and attitudes may contribute to produce placebo and nocebo effects that in turn affect the course of the disease and the response to the therapy. This article is aimed at discussing the current insights into expectations, placebo and nocebo mechanisms and their impact on the therapeutic outcomes of alcohol and drug addiction treatments; with the goal of informing physicians and other health care providers about the potentially widespread implications for clinical practice and for a successful treatment regimen. Published by Oxford University Press on behalf of Medical Council on Alcohol 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Multidisciplinary management of Paget-Schroetter syndrome. A case series of eight patients.

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Rosa Salazar, Vladimir; Otálora Valderrama, Sonia Del Pilar; Hernández Contreras, María Encarnación; García Pérez, Bartolomé; Arroyo Tristán, Andrés Del Amor; García Méndez, María Del Mar

2015-08-01

Paget-Schroetter syndrome (PSS) in the context of upper extremity deep venous thrombosis (DVT) is an uncommon but potentially very serious condition affecting young, healthy adults, in which secondary post-thrombotic syndrome (PTS) can be a complication with major implications. The best treatment option remains controversial, with current guidelines recommending anticoagulation for at least 3 months. However, an incidence of PTS of approximately 50% after 6 months, 30% after 1 year and 25% after 2 years has been found using this therapeutic approach. Consequently, specialized units recommend local thrombolysis and early decompressive surgery. We describe a series of eight cases treated in this way. None of the patients showed signs of complications, and an early return to regular activities with no PTS was observed in 90% of cases. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Severe Hyperthyroidism Complicated by Agranulocytosis Treated with Therapeutic Plasma Exchange: Case Report and Review of the Literature

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Vishnu Garla

2018-01-01

Full Text Available Aim. To present a case of Graves’ disease complicated by methimazole induced agranulocytosis treated with therapeutic plasma exchange (TPE and review of the literature. Case Presentation. A 21-year-old patient with a history of Graves’ disease presented to the endocrine clinic. His history was significant for heat intolerance, weight loss, and tremors. Upon examination he had tachycardia, smooth goiter, thyroid bruit, and hyperactive reflexes. He was started on methimazole and metoprolol and thyroidectomy was to be done once his thyroid function tests normalized. On follow-up, the patient symptoms persisted. Complete blood count done showed a white blood cell count of 2100 (4000–11,000 cells/cu mm with a neutrophil count of 400 cells/cu mm, consistent with neutropenia. He was admitted to the hospital and underwent 3 cycles of TPE and was also given filgrastim. He improved clinically and his thyroxine (T4 levels also came down. Thyroidectomy was done. He was discharged on levothyroxine for postsurgical hypothyroidism. Conclusion. Plasmapheresis may be useful in the treatment of hyperthyroidism. It works by removing protein bound hormones and also possibly inflammatory cytokines. Further studies are needed to clarify the role of various modalities of TPE in the treatment of hyperthyroidism.

Preclinical models used for immunogenicity prediction of therapeutic proteins.

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Brinks, Vera; Weinbuch, Daniel; Baker, Matthew; Dean, Yann; Stas, Philippe; Kostense, Stefan; Rup, Bonita; Jiskoot, Wim

2013-07-01

All therapeutic proteins are potentially immunogenic. Antibodies formed against these drugs can decrease efficacy, leading to drastically increased therapeutic costs and in rare cases to serious and sometimes life threatening side-effects. Many efforts are therefore undertaken to develop therapeutic proteins with minimal immunogenicity. For this, immunogenicity prediction of candidate drugs during early drug development is essential. Several in silico, in vitro and in vivo models are used to predict immunogenicity of drug leads, to modify potentially immunogenic properties and to continue development of drug candidates with expected low immunogenicity. Despite the extensive use of these predictive models, their actual predictive value varies. Important reasons for this uncertainty are the limited/insufficient knowledge on the immune mechanisms underlying immunogenicity of therapeutic proteins, the fact that different predictive models explore different components of the immune system and the lack of an integrated clinical validation. In this review, we discuss the predictive models in use, summarize aspects of immunogenicity that these models predict and explore the merits and the limitations of each of the models.

Metabolic actions of FGF21: molecular mechanisms and therapeutic implications

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Xuan Ge

2012-08-01

Full Text Available Fibroblast growth factor 21 (FGF21 is an atypical member of the FGF family that functions as an endocrine factor. In obese animals, elevation of plasma FGF21 levels by either pharmacological or genetic approaches reduces body weight, decreases hyperglycemia and hyperlipidemia, alleviates fatty liver and increases insulin sensitivity. FGF21 exerts its pleiotropic metabolic effects through its actions on multiple targets, including adipose tissue, liver, brain and pancreas. The expression of FGF21 is under the control of both peroxisome proliferator-activated receptor gamma (PPARγ and peroxisome proliferator-activated receptor alpha (PPARα. A growing body of evidence suggests that the metabolic benefits of these two nuclear receptors are mediated in part by induction of FGF21. In humans, plasma levels of FGF21 are elevated in obese subjects and patients with type 2 diabetes, but are reduced in patients with autoimmune diabetes. This review summarizes recent advances in understanding the physiological roles of FGF21 and the molecular pathways underlying its actions, and also discusses the future prospective of developing FGF21 or its agonists as therapeutic agents for obesity-related medical complications.

Inpatient Therapeutic Assessment With Narcissistic Personality Disorder.

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Hinrichs, Jon

2016-01-01

Growing evidence supporting the effectiveness of Collaborative/Therapeutic Assessment (C/TA) has led clinicians and researchers to apply C/TA to a variety of clinical populations and treatment settings. This case example presents a C/TA inpatient adaptation illustrated with narcissistic personality disorder. After a brief overview of salient concepts, I provide a detailed account of the clinical interview, test interpretation paired with diagnostic considerations specific to narcissism, planned intervention, and discussion of assessment results. Throughout the case study, I attempt to demonstrate defining features of C/TA, inpatient adaptations, and clinical techniques that encourage meaningful engagement with a "hard to reach" personality.

[Mitochondrial and microcirculatory distress syndrome in the critical patient. Therapeutic implications].

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Navarrete, M L; Cerdeño, M C; Serra, M C; Conejero, R

2013-10-01

Mitochondrial and microcirculatory distress syndrome (MMDS) can occur during systemic inflammatory response syndrome (SIRS), and is characterized by cytopathic tissue hypoxia uncorrected by oxygen transport optimization, and associated with an acquired defect in the use of oxygen and energy production in mitochondria, leading to multiple organ dysfunction (MOD). We examine the pathogenesis of MMDS, new diagnostic methods, and recent therapeutic approaches adapted to each of the three phases in the evolution of the syndrome. In the initial phase, the aim is prevention and early reversal of mitochondrial dysfunction. Once the latter is established, the aim is to restore flow of the electron chain, mitochondrial respiration, and to avoid cellular energy collapse. Finally, in the third (resolution) stage, treatment should focus on stimulating mitochondrial biogenesis and the repair or replacement of damaged mitochondria. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Mild Epicureanism: notes toward the definition of a therapeutic attitude.

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Strenger, Carlo

2008-01-01

Psychotherapists generally feel uncomfortable addressing patients' beliefs, particularly religious beliefs, because of the desire to respect client subjectivity and to avoid the abuse of therapeutic authority. This paper's first contention is that at some junctures, investigation of the client's belief structure can be an important catalyst for change, as exemplified by an extended case example. This stance assumes that much of the individual and collective damage rigid belief systems inflict derives from their function as a defense against death awareness, as described by terror management theory. The paper develops the concept of a therapeutic meta-attitude towards belief mild Epicureanism, related to the classical Greek philosopher Epicurus (341-270 BC). Mild Epicureanism means to soften attachments to all belief systems, even therapeutic theories, to lower their potential inhibition of personal growth. The paper presents the argument that mild Epicureanism is consistent with most therapeutic approaches, and allows addressing clients' belief without interfering with their right to make up their own minds.

Social Workers' Reflections on the Therapeutic Encounter With Elder Abuse and Neglect.

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Goldblatt, Hadass; Band-Winterstein, Tova; Alon, Sara

2016-02-24

The aim of this qualitative study was to explore social workers' reflections on their experience of the therapeutic encounter with victims and perpetrators of elder abuse and neglect. The research questions were as follows: How do social workers tune themselves toward the therapeutic encounter with elder abuse? How do they position themselves vis-à-vis the clients? How do social workers describe the meaning of the intervention both for the clients and for themselves? What is the added value of the therapeutic encounter in this field for the social workers? Participants were 17 experienced women social workers, who worked with abusers and with abused and neglected older adults in Israel. Data were collected via in-depth semi-structured interviews, which were later transcribed and content analyzed. Two main themes emerged from the findings, emphasizing two key aspects of the social workers' reflective process experienced during the therapeutic encounter: (a) focus on the client: "This is the journey of their lives"-reflection on the therapeutic "journey"; (b) focus on the social worker's inner and professional world: "'There is nothing to be done' is no longer in my vocabulary"-a personal and professional maturation process. The social workers expressed a positive attitude toward their elder clients. A unique dialogue developed in the therapeutic encounter, whereby the social workers considered any change as valuable if it allowed the elders a sense of control and self-worth, whereas the social workers were enriched by the elders' life experience, and matured both personally and professionally. Thus, both sides benefited from this reciprocal relationship. Implications for further research and practice are discussed. © The Author(s) 2016.

Therapeutic Change in Group Therapy For Interpersonal Trauma: A Relational Framework for Research and Clinical Practice.

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Chouliara, Zoë; Karatzias, Thanos; Gullone, Angela; Ferguson, Sandra; Cosgrove, Katie; Burke Draucker, Claire

2017-04-01

Our understanding of therapeutic change processes in group therapy for complex interpersonal trauma has been limited. The present study aimed at addressing this gap by developing a framework of therapeutic change in this field from a survivor and therapist perspective. This is a qualitative study, which utilized semistructured individual interviews. Transcripts were analyzed using interpretative phenomenological analysis (IPA) to identify recurrent themes. A final sample of n = 16 patients and n = 5 facilitators completed the interview. Main change processes identified by survivors were as follows: self versus others, trust versus threat, confrontation versus avoidance, and "patching up" versus true healing. Therapeutic processes identified by therapist facilitators included managing group dynamics, unpredictability and uncertainty, and process versus content. The proposed framework explains therapeutic change in group therapy in relational terms, that is, therapeutic dissonance, the dynamic interaction of self and experience as well as building empathic trusting relations. The importance of managing dissonance to aid personally meaningful recovery was highlighted. These findings have implications for the usefulness of relational and person-centered approaches to clinical practice in the area of interpersonal and complex trauma, especially in the early identification, prevention, and management of dropouts.

Poisons Implicated in Homicidal, Suicidal and Accidental Cases in North-West Pakistan

International Nuclear Information System (INIS)

Jan, A.; Khan, M. T. H.; Khan, M. J.; Fatima, S.; Khan, T. M.

2016-01-01

Background: Pakistan has one of the highest prevalence of poisoning in the world. However, limited data exist on the frequency of poisons implicated in homicidal, suicidal, and accidental cases in North-West Pakistan (Khyber Pakhtunkhwa). Methods: This retrospective study of 353 cases and biological specimens of poisoning received at the department of Forensic medicine and toxicology, Khyber Medical College Peshawar from 13 districts of Khyber Pakhtunkhwa. Frequency of poisoning was assessed by testing each specimen for 17 different poisons. Results: Of all the specimens, 250 (70.8 percent) specimens tested positive and the rest did not show any indication of poisoning (n=103, 29.2 percent). The most frequent poisons detected were benzodiazepines (total n=75), organophosphates (total n=58), phencyclidine (total n=30) and morphine (total n=23). Gender had a significant association with benzodiazepines (p=0.011), tricyclic antidepressants (p=0.001), and organophosphates (p<0.001). Organophosphates were the most common cause of poisoning in females while benzodiazepines were the most common cause of poisoning in males. Conclusion: Poisoning by benzodiazepines, organophosphates and phencyclidine are the most common causes of intoxication in population of Khyber Pakhtunkhwa. Source of poisoning varies with gender for organophosphates, benzodiazepines and tricyclic antidepressants. (author)

Prognostic and therapeutic implications of vascular disease in patients with atrial fibrillation

DEFF Research Database (Denmark)

Shahid, Farhan; Pastori, Daniele; Violi, Francesco

2018-01-01

of both disease states leading to a dramatic rise in future cardiovascular events. Indeed, the presence of peripheral artery disease independently predicts stroke in patients with AF. Myocardial infarction (MI) is another well-established risk factor for the development of AF; however, the role of pre...... data from clinical trials with non-vitamin K antagonist oral anticoagulants (NOACs) provided new insights on the prognostic implications of vascular disease coexistence in AF patients, and randomised trials testing a combination of NOAC with antiplatelet agents are ongoing. This review article provides...

Central venous catheters: detection of catheter complications and therapeutical options

International Nuclear Information System (INIS)

Gebauer, B.; Beck, A.; Wagner, H.J.; Vivantes-Kliniken, Hellersdorf und Prenzlauer Berg

2008-01-01

For modern medicine central venous catheters play an important role for diagnostic and therapeutic options. Catheter implantation, complication detection and therapy of catheter complications are an increasing demand for the radiologist. The review article provides an overview of different catheter types, their indications, advantages and disadvantages. Catheter malpositions are usually detectable in conventional X-ray. Most malpositions are correctable using interventional-radiological techniques. In addition therapeutical options for thrombotic complications (venous thrombosis, catheter occlusion, fibrin sheath) are discussed. In case of an infectious catheter complication, usually a catheter extraction and re-implantation is necessary

Therapeutic implications of curcumin in the prevention of diabetic retinopathy via modulation of anti-oxidant activity and genetic pathways

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Aldebasi, Yousef H; Aly, Salah M; Rahmani, Arshad H

2013-01-01

Diabetic Retinopathy (DR) is one of the most common complications of diabetes mellitus that affects the blood vessels of the retina, leading to blindness. The current approach of treatment based on anti-inflammatory, anti-angiogenesis drugs and laser photocoagulation are effective but also shows adverse affect in retinal tissues and that can even worsen the visual abilities. Thus, a safe and effective mode of treatment is needed to control or delaying the DR. Based on the earlier evidence of the potentiality of natural products as anti-oxidants, anti-diabetic and antitumor, medicinal plants may constitute a good therapeutic approach in the prevention of DR. Curcumin, constituents of dietary spice turmeric, has been observed to have therapeutic potential in the inhibition or slow down progression of DR. In this review, we summarize the therapeutic potentiality of curcumin in the delaying the DR through antioxidant, anti-inflammatory, inhibition of Vascular Endothelial Growth and nuclear transcription factors. The strength of involvement of curcumin in the modulation of genes action creates a strong optimism towards novel therapeutic strategy of diabetic retinopathy and important mainstay in the management of diabetes and its complications DR. PMID:24379904

Rescue therapeutic strategy combining ultra-protective mechanical ventilation with extracorporeal CO2 removal membrane in near-fatal asthma with severe pulmonary barotraumas: A case report.

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Pavot, Arthur; Mallat, Jihad; Vangrunderbeeck, Nicolas; Thevenin, Didier; Lemyze, Malcolm

2017-10-01

Mechanical ventilation of severe acute asthma is still considered a challenging issue, mainly because of the gas trapping phenomenon with the potential for life-threatening barotraumatic pulmonary complications. Herein, we describe 2 consecutive cases of near-fatal asthma for whom the recommended protective mechanical ventilation approach using low tidal volume of 6 mL/kg and small levels of PEEP was rapidly compromised by giant pneumomediastinum with extensive subcutaneousemphysema. Near fatal asthma. A rescue therapeutic strategy combining extracorporeal CO2 removal membrane with ultra-protective extremely low tidal volume (3 mL/kg) ventilation was applied. Both patients survived hospital discharge. These 2 cases indicate that ECCO2R associated with ultra-protective ventilation could be an alternative to surgery in case of life-threatening barotrauma occurring under mechanical ventilation.

Systemic sarcoidosis complicated of acute renal failure: about 12 cases.

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Mahfoudhi, Madiha; Mamlouk, Habiba; Turki, Sami; Kheder, Adel

2015-01-01

The sarcoidosis is a systemic granulomatosis affecting most frequently the lungs and the mediastinum. An acute renal failure reveals exceptionally this disease. It's a retrospective study implicating 12 cases of sarcoidosis complicated of acute renal failure. The aim of this study is to determine epidemiological, clinical, biological and histological profile in these cases and then to indicate the interest to consider the diagnosis of sarcoidosis in cases of unexplained renal failure. Extra-renal complications, therapeutic modalities and the outcome were determined in all patients. Our series involved 12 women with an average age of 40 years. Biological investigations showed an abnormal normocalcemia in 7 cases, a hypercalcemia in 5 cases, a hypercalciuria in 10 cases and polyclonal hypergammaglobulinemia in 7 cases. An acute renal failure was found in all patients with a median creatinin of 520 umol/L. For all patients, the renal echography was normal however, the kidney biopsy showed tubulo-interstitial nephritis. The extra-renal signs highlighting pulmonary interstitial syndrome in 5 cases, a sicca syndrome in 4 cases, mediastinal lymph nodes in 2 cases, a lymphocytic alveolitis in 3 cases, an anterior granulomatous uveitis in 2 cases and a polyarthritis in 5 cases. Five patients benefited of hemodialysis. The treatment consisted of corticosteroid in all cases. The follow up was marked by complete resolution of clinical and biological signs. The diagnosis of renal sarcoidosis must be done quickly to prevent renal failure.

Therapeutic abortion follow-up study.

Science.gov (United States)

Margolis, A J; Davison, L A; Hanson, K H; Loos, S A; Mikkelsen, C M

1971-05-15

To determine the long-range psychological effects of therapeutic abortion, 50 women (aged from 13-44 years), who were granted abortions between 1967 and 1968 Because of possible impairment of mental and/or physical health, were analyzed by use of demographic questionnaires, psychological tests, and interviews. Testing revealed that 44 women had psychiatric problems at time of abortion. 43 patients were followed for 3-6 months. The follow-up interviews revealed that 29 patients reacted positively after abortion, 10 reported no significant change and 4 reacted negatively. 37 would definitely repeat the abortion. Women under 21 years of age felt substantially more ambivalent and guilty than older patients. A study of 36 paired pre- and post-abortion profiles showed that 15 initially abnormal tests had become normal. There was a significant increase in contraceptive use among the patients after the abortion, but 4 again became pregnant and 8 were apparently without consistent contraception. It is concluded that the abortions were therapeutic, but physicians are encouraged to be aware of psychological problems in abortion cases. Strong psychological and contraceptive counselling should be exercised.

Fight malaria at home: Therapeutic and prophylaxis clinical data

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Deepak Bhattacharya

2011-06-01

Full Text Available Objective: To identify a new, safe and effective source to combat and prevent drug resistant malaria therapeutically and to make it as a home-made bio-medicine which is called as OMARIA (Orissa malaria research indigenous attempt and use it on long term basis (decade in mono clinical station and in field. Methods: The rind of a lesser known Indian indigenous fruit dalimba/ Punica granatum (P. granatum is taken. Manual process to make a hand-made or home-made bio-medicine is done. Hand-filled into gelatin capsules and administered as an internal medicine. Therapy to 532 clinical cases is given at the Govt Red Cross Clinic, and Prophylaxis at site is administered to 401 cases by adopting 3 villages. Results: Hydrophyllic, ellagitannins viz., punicalagin (C 48H28O 30; mw 1 1 00~1 1 25, punicalin (C 34H22O 22; mw 780~785, ellagic acid (C14H6O8; mw 302 and K+ co-exists as the only drug moieties. OMARIA has no other confounding or confabulating compounds. There is non alkaloid. Conclusions: OMARIA delivers therapeutics and prophylaxis to drug resistant Plasmodium falciparum (P. falciparum cases. There are no side effects and no contradictions. Non-toxic at bolus/loading doses. No case progressed to cerebral malaria. OMARIA is a first time work. Original report on pan global basis.

The results of therapeutic plasma exchange in patients with severe hyperthyroidism: a retrospective multicenter study.

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Keklik, Muzaffer; Kaynar, Leylagul; Yilmaz, Mehmet; Sivgin, Serdar; Solmaz, Musa; Pala, Cigdem; Aribas, Sulbiye; Akyol, Gulsah; Unluhizarci, Kursat; Cetin, Mustafa; Eser, Bulent; Unal, Ali

2013-06-01

Hyperthyroidism characterized by elevated serum levels of circulating thyroid hormones. The aim of hyperthyroidism treatment is to achieve a euthyroid state as soon as possible and to maintain euthyroid status. However, drug withdrawal and utilization of alternative therapies are needed in cases in which leucopenia or impairment in liver functions is observed during medical therapy. In the present study, we aimed to present our cases which underwent therapeutic plasma exchange (TPE) due to severe hyperthyroidism. The results of 22 patients who underwent therapeutic plasma exchange due to hyperthyroidism in Apheresis Units of Erciyes University and Gaziantep University, between 2006 and 2012, were retrospectively reviewed. These cases had severe thyrotoxic values despite anti-thyroid drug use. After TPE, we observed a significant decrease in free thyroxin (FT4) (phyperthyroidism by TPE in 20 cases (91%). Both FT3 and FT4 levels remained above the normal limits in two of 22 patients. TPE should be considered as an effective and safe therapeutic option to achieve euthyroid state before surgery or radioactive iodine treatment. TPE is a useful option in cases with severe hyperthyroidism unresponsive to anti-thyroid agents and in those with clinical manifestations of cardiac failure and in patients with severe adverse events during anti-thyroid therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ebola Virus Altered Innate and Adaptive Immune Response Signalling Pathways: Implications for Novel Therapeutic Approaches.

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Kumar, Anoop

2016-01-01

Ebola virus (EBOV) arise attention for their impressive lethality by the poor immune response and high inflammatory reaction in the patients. It causes a severe hemorrhagic fever with case fatality rates of up to 90%. The mechanism underlying this lethal outcome is poorly understood. In 2014, a major outbreak of Ebola virus spread amongst several African countries, including Leone, Sierra, and Guinea. Although infections only occur frequently in Central Africa, but the virus has the potential to spread globally. Presently, there is no vaccine or treatment is available to counteract Ebola virus infections due to poor understanding of its interaction with the immune system. Accumulating evidence indicates that the virus actively alters both innate and adaptive immune responses and triggers harmful inflammatory responses. In the literature, some reports have shown that alteration of immune signaling pathways could be due to the ability of EBOV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. On the other hand, some reports have demonstrated that EBOV, VP35 proteins act as interferon antagonists. So, how the Ebola virus altered the innate and adaptive immune response signaling pathways is still an open question for the researcher to be explored. Thus, in this review, I try to summarize the mechanisms of the alteration of innate and adaptive immune response signaling pathways by Ebola virus which will be helpful for designing effective drugs or vaccines against this lethal infection. Further, potential targets, current treatment and novel therapeutic approaches have also been discussed.

Case Study: The Myanmar and Bangladesh Maritime Boundary Dispute in the Bay of Bengal and Its Implications for South China Sea Claims

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Ravi A. Balaram

2012-01-01

Full Text Available This paper seeks to review the pertinent Myanmar and Bangladesh history in overlapping maritime territorial claims leading up to the September 2011 International Tribunal for the Law of the Sea (ITLOS case: Dispute Concerning Delimitation of the Maritime Boundary Between Bangladesh and Myanmar in the Bay of Bengal. It will dissect the legal proceedings as primary source documents and apply the relevant judgement findings to analyse the implications for the respective countries and for South China Sea maritime boundary disputes. While the judgements of this case set certain legal precedents that may be more easily applied to bilateral disputes, the implications, nevertheless, impinge on multilateral claims as well. To the extent that the Bangladesh-Myanmar ITLOS judgement provides a pathway to third-party, independent, and peaceful resolution to the potentially explosive and escalating tensions in the South China Sea, this paper argues that findings are relevant, but limited.

Public health implications of lead poisoning in backyard chickens and cattle: four cases

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Roegner A

2013-04-01

Full Text Available Amber Roegner,1 Federico Giannitti,2 Leslie W Woods,2 Asli Mete,2 Birgit Puschner1,2 1Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA; 2California Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California, Davis, CA, USA Abstract: Lead intoxication in livestock has historically been associated with cattle turned out to pasture and accidental ingestion of lead from drinking crankcase oil, licking grease from machinery, chewing on plumbing or batteries, or drinking water contaminated from leaching materials. Even with the decrease in manufactured items produced with lead, contaminants persist in the landscape and may enter the food supply through animal products. Changing patterns of open range herds moving to new pasture and the increased popularity of urban/suburban backyard chickens or other livestock necessitates public awareness about the clinical signs of lead intoxication, the potential for subclinical animals, public health concerns, particularly for exposure in children, and testing options available. Cases of lead intoxication in livestock demand a thorough case work-up to identify all sources of lead, address subclinical cases, evaluate risk to consumers, and make management suggestions for future prevention. We discuss four recent cases of confirmed lead poisoning in backyard chickens and open range cattle and assess the public health implications therein. Taken as a whole and considering the potential of the remaining herd or flock to be affected without necessarily showing signs, public health officials and veterinarians should be prepared to advise clients on case work-up and management and prevention considerations. Backyard chickens and cattle may not present for suspected lead poisoning as in several of the cases discussed herein yet may still contain concerning tissue or blood levels. The authors believe increased

Engineering responsive supramolecular biomaterials: Toward smart therapeutics.

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Webber, Matthew J

2016-09-01

Engineering materials using supramolecular principles enables generalizable and modular platforms that have tunable chemical, mechanical, and biological properties. Applying this bottom-up, molecular engineering-based approach to therapeutic design affords unmatched control of emergent properties and functionalities. In preparing responsive materials for biomedical applications, the dynamic character of typical supramolecular interactions facilitates systems that can more rapidly sense and respond to specific stimuli through a fundamental change in material properties or characteristics, as compared to cases where covalent bonds must be overcome. Several supramolecular motifs have been evaluated toward the preparation of "smart" materials capable of sensing and responding to stimuli. Triggers of interest in designing materials for therapeutic use include applied external fields, environmental changes, biological actuators, applied mechanical loading, and modulation of relative binding affinities. In addition, multistimuli-responsive routes can be realized that capture combinations of triggers for increased functionality. In sum, supramolecular engineering offers a highly functional strategy to prepare responsive materials. Future development and refinement of these approaches will improve precision in material formation and responsiveness, seek dynamic reciprocity in interactions with living biological systems, and improve spatiotemporal sensing of disease for better therapeutic deployment.

Structurally Based Therapeutic Evaluation: A Therapeutic and Practical Approach to Teaching Medicinal Chemistry.

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Alsharif, Naser Z.; And Others

1997-01-01

Explains structurally based therapeutic evaluation of drugs, which uses seven therapeutic criteria in translating chemical and structural knowledge into therapeutic decision making in pharmaceutical care. In a Creighton University (Nebraska) medicinal chemistry course, students apply the approach to solve patient-related therapeutic problems in…

Implication of Heat Shock Factors in Tumorigenesis: Therapeutical Potential

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Thonel, Aurelie de [INSERM U866, Dijon (France); Faculty of Medicine and Pharmacy, University of Burgundy, 21033 Dijon (France); Mezger, Valerie, E-mail: valerie.mezger@univ-paris-diderot.fr [CNRS, UMR7216 Epigenetics and Cell Fate, Paris (France); University Paris Diderot, 75013 Paris (France); Garrido, Carmen, E-mail: valerie.mezger@univ-paris-diderot.fr [INSERM U866, Dijon (France); Faculty of Medicine and Pharmacy, University of Burgundy, 21033 Dijon (France); CHU, Dijon BP1542, Dijon (France)

2011-03-07

Heat Shock Factors (HSF) form a family of transcription factors (four in mammals) which were named according to the discovery of their activation by a heat shock. HSFs trigger the expression of genes encoding Heat Shock Proteins (HSPs) that function as molecular chaperones, contributing to establish a cytoprotective state to various proteotoxic stresses and in pathological conditions. Increasing evidence indicates that this ancient transcriptional protective program acts genome-widely and performs unexpected functions in the absence of experimentally defined stress. Indeed, HSFs are able to re-shape cellular pathways controlling longevity, growth, metabolism and development. The most well studied HSF, HSF1, has been found at elevated levels in tumors with high metastatic potential and is associated with poor prognosis. This is partly explained by the above-mentioned cytoprotective (HSP-dependent) function that may enable cancer cells to adapt to the initial oncogenic stress and to support malignant transformation. Nevertheless, HSF1 operates as major multifaceted enhancers of tumorigenesis through, not only the induction of classical heat shock genes, but also of “non-classical” targets. Indeed, in cancer cells, HSF1 regulates genes involved in core cellular functions including proliferation, survival, migration, protein synthesis, signal transduction, and glucose metabolism, making HSF1 a very attractive target in cancer therapy. In this review, we describe the different physiological roles of HSFs as well as the recent discoveries in term of non-cogenic potential of these HSFs, more specifically associated to the activation of “non-classical” HSF target genes. We also present an update on the compounds with potent HSF1-modulating activity of potential interest as anti-cancer therapeutic agents.

Implication of Heat Shock Factors in Tumorigenesis: Therapeutical Potential

International Nuclear Information System (INIS)

Thonel, Aurelie de; Mezger, Valerie; Garrido, Carmen

2011-01-01

Heat Shock Factors (HSF) form a family of transcription factors (four in mammals) which were named according to the discovery of their activation by a heat shock. HSFs trigger the expression of genes encoding Heat Shock Proteins (HSPs) that function as molecular chaperones, contributing to establish a cytoprotective state to various proteotoxic stresses and in pathological conditions. Increasing evidence indicates that this ancient transcriptional protective program acts genome-widely and performs unexpected functions in the absence of experimentally defined stress. Indeed, HSFs are able to re-shape cellular pathways controlling longevity, growth, metabolism and development. The most well studied HSF, HSF1, has been found at elevated levels in tumors with high metastatic potential and is associated with poor prognosis. This is partly explained by the above-mentioned cytoprotective (HSP-dependent) function that may enable cancer cells to adapt to the initial oncogenic stress and to support malignant transformation. Nevertheless, HSF1 operates as major multifaceted enhancers of tumorigenesis through, not only the induction of classical heat shock genes, but also of “non-classical” targets. Indeed, in cancer cells, HSF1 regulates genes involved in core cellular functions including proliferation, survival, migration, protein synthesis, signal transduction, and glucose metabolism, making HSF1 a very attractive target in cancer therapy. In this review, we describe the different physiological roles of HSFs as well as the recent discoveries in term of non-cogenic potential of these HSFs, more specifically associated to the activation of “non-classical” HSF target genes. We also present an update on the compounds with potent HSF1-modulating activity of potential interest as anti-cancer therapeutic agents

Consequences of radiopharmaceutical extravasation and therapeutic interventions: a systematic review

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Pol, Jochem van der; Voeoe, Stefan [Maastricht University Medical Centre (MUMC+), Department of Radiology and Nuclear Medicine, Postbox 5800, Maastricht (Netherlands); Bucerius, Jan; Mottaghy, Felix M. [Maastricht University Medical Centre (MUMC+), Department of Radiology and Nuclear Medicine, Postbox 5800, Maastricht (Netherlands); University Hospital, RWTH Aachen University, Department of Nuclear Medicine, Aachen (Germany)

2017-07-15

Radiopharmaceutical extravasation can potentially lead to severe soft tissue damage, but little is known about incidence, medical consequences, possible interventions, and effectiveness of these. The aims of this study are to estimate the incidence of extravasation of diagnostic and therapeutic radiopharmaceuticals, to evaluate medical consequences, and to evaluate medical treatment applied subsequently to those incidents. A sensitive and elaborate literature search was performed in Embase and PubMed using the keywords ''misadministration'', ''extravasation'', ''paravascular infiltration'', combined with ''tracer'', ''radionuclide'', ''radiopharmaceutical'', and a list of keywords referring to clinically used tracers (i.e. ''Technetium-99m'', ''Yttrium-90''). Reported data on radiopharmaceutical extravasation and applied interventions was extracted and summarised. Thirty-seven publications reported 3016 cases of diagnostic radiopharmaceutical extravasation, of which three cases reported symptoms after extravasation. Eight publications reported 10 cases of therapeutic tracer extravasation. The most severe symptom was ulceration. Thirty-four different intervention and prevention strategies were performed or proposed in literature. Extravasation of diagnostic radiopharmaceuticals is common. {sup 99m}Tc, {sup 123}I, {sup 18}F, and {sup 68}Ga labelled tracers do not require specific intervention. Extravasation of therapeutic radiopharmaceuticals can give severe soft tissue lesions. Although not evidence based, surgical intervention should be considered. Furthermore, dispersive intervention, dosimetry and follow up is advised. Pharmaceutical intervention has no place yet in the immediate care of radiopharmaceutical extravasation. (orig.)

Shigella Vulvovaginitis in Childhood: A Case Report

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Rajkumar, Solomon; Narayanaswamy, Geetha; Laude, Teresita Awa

1979-01-01

Vulvovaginitis due to Shigella sonnei is reported in a four-year-old child. Shigella sonnei as a rare primary pathogen causing vulvovaginitis, the prolonged nature of the clinical course, and the therapeutic implications of increasing resistance to ampicillin by the organism are discussed. PMID:395325

FDG PET evaluation of therapeutic response and toxicity after radiotherapy for NSCLC

International Nuclear Information System (INIS)

Hicks, R.J.; MacManus, M.P.; Matthews, J.P.; Rischin, D.; Binns, D.; McKenzie, A.F.; Ball, D.L.

2002-01-01

Full text: Positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) is recognised for staging and therapeutic planning of patients with non-small cell carcinoma of the lung (NSCLC). The potential for this technique to be used in the assessment of therapeutic response has also been highlighted but may be limited by false positive results due to inflammatory response, particularly early after radiotherapy (RT). To evaluate the utility of FEX PET for therapeutic monitoring early (<12 weeks) after completion of radical RT we prospectively evaluated metabolic response and radiation toxicity using a standardised scoring system in 73 consecutive patients. All 73 had evaluable PET scans but 6 of the CT scan results were considered non-evaluable for therapeutic response using WHO criteria. PET therapeutic response category differed from that by CT in 40/67 (60%) cases and in 80% of such cases suggested a more marked response than suggested by CT (p 0.0002). Multifactor analysis including PET response, CT response, performance status, weight loss and stage revealed that PET response was the only significant predictor of survival (p 0.0001). Radiation toxicity scores were inversely related to therapeutic response on both PET (p = 0.022) and CT (p =0.029). In particular, more severe (grade 2 or 3) radiotoxicity scores on PET were associated with a greater proportion of partial or complete responses on both PET and CT than were lower (grade 0 and 1) scores (p =0.0044 and 0.041 respectively) consistent with the known relationship between the radiosensitivity of normal host and tumoral tissues. Early after completion of radiotherapy for NSCLC, PET response provides better prognostic stratification than CT response. PET can also identify typical radiation toxicity changes which are associated with response to treatment. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

Therapeutic bronchoscopy in a child with sand aspiration and respiratory failure from near drowning--case report and literature review.

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Kapur, N; Slater, A; McEniery, J; Greer, M L; Masters, I B; Chang, A B

2009-10-01

Foreign matter aspiration occurs relatively commonly in drowning and near-drowning events. In most cases, stomach contents are aspirated. Sand aspiration rarely occurs and there are no reported cases in children with near drowning. Limited data are available on clinical presentation and management of sand aspiration with accidental burial. We report a 3-year-old boy who nearly drowned while swimming in brackish waters and was found face down in sand. Sand aspiration was suspected when the child continued to have persistent wheezing and high ventilatory requirement despite intensive bronchodilator and corticosteroids therapy with an inability to wean after 4 days post-near-drowning event. Radiology was non-specific in the absence of sand bronchogram. Presence of sand in the airways was confirmed when a bronchoscopy was undertaken and sand seen in the bronchoalveolar lavage fluid. Sequential lung washing followed by exogenous surfactant administration (3 ml/kg) was undertaken and lead to significant improvement such that within 12 hr post-therapeutic lavage, his ventilatory requirements reduced substantially. The child was extubated 4 days post-lavage and on review 2 months post-event, was clinically well with airway resistance within normal predicted values measured on forced oscillatory spirometry (IOS).

Design of therapeutic vaccines as a novel antibody therapy for cardiovascular diseases.

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Nakagami, Hironori

2017-09-01

Vaccines are primarily used worldwide as a preventive medicine for infectious diseases and have recently been applied to cancer. We and others have developed therapeutic vaccines designed for cardiovascular diseases that are notably different from previous vaccines. In the case of cancer vaccines, a specific protein in cancer cells is a target antigen, and the activation of cytotoxic T cells (CTL) is required to kill and remove the antigen-presenting cancer cells. Our therapeutic vaccines work against hypertension by targeting angiotensin II (Ang II) as the antigen, which is an endogenous hormone. Therapeutic vaccines must avoid CTL activation and induce the blocking antibodies for Ang II. The goal of our therapeutic vaccine for cardiovascular diseases is to induce the specific antibody response toward the target protein without inducing T-cell or antibody-mediated inflammation through the careful selection of the target antigen, carrier protein and adjuvants. The goal of our therapeutic vaccine is similar to that of antibody therapy. Recently, multiple antibody-based drugs have been developed for cancer, immune-related diseases, and dyslipidemia, which are efficient but expensive. If the effect of a therapeutic vaccine is nearly equivalent to antibody therapy as an alternative approach, the lower medical cost and improvement in drug adherence can be advantages of therapeutic vaccines. In this review, we will describe our concept of therapeutic vaccines for cardiovascular diseases and the future directions of therapeutic vaccines as novel antibody therapies. Copyright © 2017. Published by Elsevier Ltd.

A rare case of persistent metopic suture in an elderly individual: Incidental autopsy finding with clinical implications

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S Vikram

2014-01-01

Full Text Available Metopic suture is a dense fibrous joint extending from the nasion to the bregma. Normally, closure of this suture takes place between 1-8 years of age. Failure of this closure beyond 8 years leads to persistent metopic suture. A rare case of persistent metopic suture in a 60-year-old male is documented, who committed suicide by alleged consumption of organophosphorous compound at District Govt. Wenlock Hospital, Mangalore, Karnataka, India. Metopic suture may mimic skull fracture and may mislead an inexperienced forensic expert. Neurosurgeon should also be aware of this anatomical variation while performing frontal craniotomy, as the persistent metopic suture may mimic vertical fracture of the skull. Hence, in this case report, the clinical and medico-legal implications of the persistent metopic sutures have been discussed.

Conservative therapeutic management of carpal tunnel syndrome

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Roberto Sérgio Martins

Full Text Available ABSTRACT Carpal tunnel syndrome is the most prevalent nerve compression and can be clinically or surgically treated. In most cases, the first therapeutic alternative is conservative treatment but there is still much controversy regarding the most effective modality of this treatment. In this study, we critically evaluated the options of conservative treatment for carpal tunnel syndrome, aiming to guide the reader through the conventional options used in this therapy.

Therapeutic benefits of ACTH and levetiracetam in STXBP1 encephalopathy with a de novo mutation: A case report and literature review.

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Liu, Shunli; Wang, Liyuan; Cai, Xiao Tang; Zhou, Hui; Yu, Dan; Wang, Zhiling

2018-05-01

The case report aims to discuss the clinical symptoms and treatment of encephalopathy caused by a novel syntaxin- binding protein 1 (STXBP1) genetic mutation. The patient, a girl, was born at 38+4 weeks of gestation. She had frequent spasm attacks accompanied by obvious psychomotor development retardation since the neonatal period. Genetic screening identified a novel STXBP1 genetic mutation. Early-onset epileptic encephalopathy with STXBP1 mutation. We adjusted the antiepileptic strategy to oral levetiracetam and topiramate, and intravenous administration of adrenocorticotropic hormone(ACTH) for 2 weeks. Subsequently, prednisone was continued, and gradually reduced and withdrawn over 3 months. The treatment was effective with complete control of the epileptic seizures and improvements in the electroencephalogram readings. However, the effects on psychomotor ability were slow and limited. A literature review of STXBP1 mutation cases in which ACTH was administered showed that complete seizure control is observed in 60% of cases, 20% are partially affected, and the remaining 20% show no effect. ACTH and levetiracetam had good therapeutic effects in epilepsy control in this case of de novo STXBP1 mutation. ACTH is an effective drug for early-onset epileptic encephalopathy caused by STXBP1 mutation. However, controlling epilepsy using this therapy does not alter the psychomotor development retardation caused by the STXBP1 mutation.

Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases

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Hideyuki eTakeuchi

2014-09-01

Full Text Available Microglia are macrophage-like resident immune cells that contribute to the maintenance of homeostasis in the central nervous system (CNS. Abnormal activation of microglia can cause damage in the CNS, and accumulation of activated microglia is a characteristic pathological observation in neurologic conditions such as trauma, stroke, inflammation, epilepsy, and neurodegenerative diseases. Activated microglia secrete high levels of glutamate, which damages CNS cells and has been implicated as a major cause of neurodegeneration in these conditions. Glutamate-receptor blockers and microglia inhibitors (e.g. minocycline have been examined as therapeutic candidates for several neurodegenerative diseases; however, these compounds exerted little therapeutic benefit because they either perturbed physiological glutamate signals or suppressed the actions of protective microglia. The ideal therapeutic approach would hamper the deleterious roles of activated microglia without diminishing their protective effects. We recently found that abnormally activated microglia secrete glutamate via gap-junction hemichannels on the cell surface. Moreover, administration of gap-junction inhibitors significantly suppressed excessive microglial glutamate release and improved disease symptoms in animal models of neurologic conditions such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer’s disease. Recent evidence also suggests that neuronal and glial communication via gap junctions amplifies neuroinflammation and neurodegeneration. Elucidation of the precise pathologic roles of gap junctions and hemichannels may lead to a novel therapeutic strategies that can slow and halt the progression of neurodegenerative diseases.

Aerosol exposure to Rift Valley fever virus causes earlier and more severe neuropathology in the murine model, which has important implications for therapeutic development.

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Christopher Reed

Full Text Available Rift Valley fever virus (RVFV is an important mosquito-borne veterinary and human pathogen that can cause severe disease including acute-onset hepatitis, delayed-onset encephalitis, retinitis and blindness, or a hemorrhagic syndrome. Currently, no licensed vaccine or therapeutics exist to treat this potentially deadly disease. Detailed studies describing the pathogenesis of RVFV following aerosol exposure have not been completed and candidate therapeutics have not been evaluated following an aerosol exposure. These studies are important because while mosquito transmission is the primary means for human infection, it can also be transmitted by aerosol or through mucosal contact. Therefore, we directly compared the pathogenesis of RVFV following aerosol exposure to a subcutaneous (SC exposure in the murine model by analyzing survival, clinical observations, blood chemistry, hematology, immunohistochemistry, and virus titration of tissues. Additionally, we evaluated the effectiveness of the nucleoside analog ribavirin administered prophylactically to treat mice exposed by aerosol and SC. The route of exposure did not significantly affect the survival, chemistry or hematology results of the mice. Acute hepatitis occurred despite the route of exposure. However, the development of neuropathology occurred much earlier and was more severe in mice exposed by aerosol compared to SC exposed mice. Mice treated with ribavirin and exposed SC were partially protected, whereas treated mice exposed by aerosol were not protected. Early and aggressive viral invasion of brain tissues following aerosol exposure likely played an important role in ribavirin's failure to prevent mortality among these animals. Our results highlight the need for more candidate antivirals to treat RVFV infection, especially in the case of a potential aerosol exposure. Additionally, our study provides an account of the key pathogenetic differences in RVF disease following two potential

Isolated persistent left superior vena cava: A case report and its clinical implications

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Samarjit Bisoyi

2017-01-01

Full Text Available The venous anomaly of a persistent left superior vena cava (PLSVC affects 0.3%-0.5% of the general population. PLSVC with absent right superior vena cava, also termed as "isolated PLSVC," is an extremely rare venous anomaly. Almost half of the patients with isolated PLSVC have cardiac anomalies in the form of atrial septal defect, endocardial cushion defects, or tetralogy of Fallot. Isolated PLSVC is usually innocuous. Its discovery, however, has important clinical implications. It can pose clinical difficulties with central venous access, cardiothoracic surgeries, and pacemaker implantation. When it drains to the left atrium, it may create a right to left shunt. In this case report, we present the incidental finding of isolated PLSVC in a patient who underwent aortic valve replacement. Awareness about this condition and its variations is important to avoid complications.

Polyarticular gout attacks following cerebrovascular accidents: is hemiparesis in fact protective? 2 cases and a review of the literature.

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Hsiao, Susan J; Vaynrub, Maksim; Furer, Victoria; Samuels, Jonathan

2010-09-01

Cerebrovascular disease appears to have implications on rheumatic diseases, including gout. Accumulating evidence suggests that hemiparesis exerts a protective effect against gout via the down-regulation of mechanical and neural modulators of inflammation in neurologically impaired extremities. We present 2 divergent cases of unilateral gout following cerebrovascular events. One patient with a hemorrhagic stroke developed polyarticular gout only on the ipsilateral side to his hemiparesis, while another patient with basilar artery thrombosis and locked-in syndrome suffered a polyarticular gout flare only on the side that had regained limited function. As suggested by these cases, the effect of hemiparesis on gout is complex. Further insight into the interplay between gouty flares and hemiparesis may lead to novel therapeutic strategies for gout.

[Thoracic wounds. Therapeutic approach. Apropos of 77 cases].

Science.gov (United States)

Lamour, A; Azorin, J; Destable, M D; Hoang, P; Lapandry, C; de Saint-Florent, G

1987-05-01

We have led over a four year period, from 1981 to 1985, a prospective study on all cases of penetrating chest wounds (77 cases) in the intensive Care unit and the Department of Thoracic Surgery at the Avicenne Hospital. These wounds, involving young males, are fortunately mostly benign. Their seriousness is based on the abdominal or mediastinal hemorrhage as well as lesions to the vital organs which need an emergency intervention. The latter, nevertheless, with the help of the mobile reanimation service for transfering the patient, has diminished the mortality rate to 2.6 per cent. Following their experiment and after a review of the literature, the authors expose their method of management of the penetrating chest wounds.

Idiopathic granulomatous mastitis: in search of a therapeutic paradigm.

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Wilson, Jason P; Massoll, Nicole; Marshall, Julia; Foss, Robin M; Copeland, Edward M; Grobmyer, Stephen R

2007-08-01

Idiopathic granulomatous mastitis, also known as idiopathic granulomatous lobular mastitis, is a benign breast lesion that represents both a diagnostic and therapeutic dilemma. We report two cases of granulomatous mastitis recently evaluated and managed at our institution. To better understand this rare disease, we analyzed treatment outcomes in reported cases of granulomatous mastitis. One hundred sixteen cases were subsequently analyzed. Primary management strategies included observation (n = 9), steroids (n = 29), partial mastectomy (n = 75), and mastectomy (n = 3). Success rates with each treatment were observation, 56 per cent; steroids, 42 per cent; partial mastectomy, 79 per cent; and mastectomy, 100 per cent. Based on this analysis, we propose a clinically useful algorithm for both workup and management of these challenging cases.

Modelling hemoglobin and hemoglobin:haptoglobin complex clearance in a non-rodent species– pharmacokinetic and therapeutic implications

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Felicitas S Boretti

2014-10-01

Full Text Available Preclinical studies suggest that haptoglobin (Hp supplementation could be an effective therapeutic modality during acute or chronic hemolytic diseases. Hp prevents Hb extravasation and neutralizes Hb’s oxidative and NO scavenging activity in the vasculature. Small animal models such as mouse, rat and guinea pig appear to be valuable to provide proof-of-concept for Hb neutralization by Hp in diverse pre-clinical conditions. However, these species differ significantly from human in the clearance of Hb:Hp complexes, which leads to long persistence of circulating Hb:Hp complexes after administration of human plasma derived Hp. Alternative animal models must therefore be explored to guide pre-clinical development of these potential therapeutics. In contrast to rodents, dogs have high Hp plasma concentrations comparable to human. In this study we show that like human macrophages, dog peripheral blood monocyte derived macrophages express a glucocorticoid inducible endocytic clearance pathways with a high specificity for the Hb:Hp complex. Evaluating the Beagle dog as a non-rodent model species we provide the first pharmacokinetic parameter estimates of free Hb and Hb:Hp phenotype complexes. The data reflect a drastically reduced volume of distribution (Vc of the complex compared to free Hb, increased exposures (Cmax and AUC and significantly reduced total body clearance (CL with a terminal half-life (t1/2 of approximately 12 hours. Distribution and clearance was identical for dog and human Hb (± glucocorticoid stimulation and for dimeric and multimeric Hp preparations bound to Hb. Collectively, our study supports the dog as a non-rodent animal model to study pharmacological and pharmacokinetic aspects of Hb clearance systems and apply the model to studying Hp therapeutics.

A Case Report of Hodgkin’s Lymphoma in a Patient with Carcinosarcoma of the Bladder

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Anthony Perre

2011-12-01

Full Text Available The screening of patients with a known primary extrathoracic malignancy for pulmonary metastasis may result in the identification of solitary or multiple pulmonary nodules. Radiologic features of these pulmonary nodules may suggest a diagnosis, but these features cannot reliably distinguish between benign and malignant etiologies. We present the case of a patient, diagnosed with carcinosarcoma of the bladder, who was found to have multiple pulmonary nodules by CT evaluation. Physical examination of the patient demonstrated the presence of cervical and axillary lymphadenopathy. An excisional biopsy of an axillary lymph node confirmed the diagnosis of Hodgkin’s lymphoma. This case report demonstrates that radiographic information obtained by CT scan must be carefully correlated with the history and physical examination of the patient. This case report also demonstrates the importance of diagnostic biopsy of pulmonary nodularity discovered in patients with a known primary extrathoracic malignancy. The assumption that these pulmonary nodules represented metastatic malignancies would have had crucial prognostic and therapeutic implications.

Genetics of rare mesenchymal tumors: implications for targeted treatment in DFSP, ASPS, CCS, GCTB and PEComa.

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Rutkowski, Piotr; Przybył, Joanna; Świtaj, Tomasz

2014-08-01

Soft tissue and bone sarcomas comprise a heterogeneous group of mesenchymal tumors that include roughly 130 distinct diagnostic entities. Many of them are exceptionally rare, with only few cases diagnosed worldwide each year. Development of novel targeted treatment in this group of tumors is of special importance since many sarcoma subtypes are resistant to conventional chemotherapy and the effective therapeutic options are limited. In this review we aim to discuss the molecular implications for targeted therapy in selected rare soft tissue and bone sarcoma subtypes, including dermatofibrosarcoma protuberans (DFSP), alveolar soft part sarcoma (ASPS), clear cell sarcoma (CCS), giant cell tumor of bone (GCTB) and perivascular epithelioid cell neoplasms (PEComas). This article is part of a Directed Issue entitled: Rare cancers. Copyright © 2014 Elsevier Ltd. All rights reserved.

In vitro and in vivo delivery of therapeutic proteins using cell penetrating peptides.

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Bolhassani, Azam; Jafarzade, Behnaz Sadat; Mardani, Golnaz

2017-01-01

The failure of proteins to penetrate mammalian cells or target tumor cells restricts their value as therapeutic tools in a variety of diseases such as cancers. Recently, protein transduction domains (PTDs) or cell penetrating peptides (CPPs) have been shown to promote the delivery of therapeutic proteins or peptides into live cells. The successful delivery of proteins mainly depends on their physicochemical properties. Although, linear cell penetrating peptides are one of the most effective delivery vehicles; but currently, cyclic CPPs has been developed to potently transport bioactive full-length proteins into cells. Up to now, several small protein transduction domains from viral proteins including Tat or VP22 could be fused to other peptides or proteins to entry them in various cell types at a dose-dependent approach. A major disadvantage of PTD-fusion proteins is primary uptake into endosomal vesicles leading to inefficient release of the fusion proteins into the cytosol. Recently, non-covalent complex formation (Chariot) between proteins and CPPs has attracted a special interest to overcome some delivery limitations (e.g., toxicity). Many preclinical and clinical trials of CPP-based delivery are currently under evaluation. Generally, development of more efficient protein transduction domains would significantly increase the potency of protein therapeutics. Moreover, the synergistic or combined effects of CPPs with other delivery systems for protein/peptide drug delivery would promote their therapeutic effects in cancer and other diseases. In this review, we will describe the functions and implications of CPPs for delivering the therapeutic proteins or peptides in preclinical and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Therapeutic potential of agmatine for CNS disorders.

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Neis, Vivian B; Rosa, Priscila B; Olescowicz, Gislaine; Rodrigues, Ana Lúcia S

2017-09-01

Agmatine is a neuromodulator that regulates multiple neurotransmitters and signaling pathways. Several studies have focused on elucidating the mechanisms underlying the neuroprotective effects of this molecule, which seems to be mediated by a reduction in oxidative damage, neuroinflammation, and proapoptotic signaling. Since these events are implicated in acute and chronic excitotoxicity-related disorders (ischemia, epilepsy, traumatic brain injury, spinal cord injury, neurodegenerative, and psychiatric disorders) as well as in nociception, agmatine has been proposed as a therapeutic strategy for the treatment of central nervous system (CNS) disorders. Agmatine also stimulates the expression of trophic factors and adult neurogenesis, contributing to its ability to induce endogenous repair mechanisms. Therefore, considering its wide range of biological effects, this review summarizes the current knowledge about its protective and regenerative properties in the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pathogenesis of Graves` disease and therapeutic implications; Pathogenese des Morbus Basedow und therapeutische Implikationen

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Seif, F.J. [Tuebingen Univ. (Germany). Medizinische Klinik und Poliklinik

1997-12-01

Graves` disease presents itself clinically mainly as hyperthyroidism and infiltrative ophthalmopathy and to a minimal extent also as dermopathy and acropachy. Autoimmune processes are the basic pathogenesis. Stimulating antibodies against the TSH receptor cause hyperthyroidism. Autoantibodies and autoreactive T lymphocytes against primarily thyroidal antigens cross-react with similar antigens of the eye muscles and orbital connective tissue, thus spreading the disease from the thyroid to the eyes. The therapeutic goal comprises not only the treatment of hyperthyroidism, but also the induction of a steady immuntolerance in order to minimize the irreversible damage to the eye. The therapeutic armamentarium is formed by antithyroid drugs, glucocorticoids, retrobulbar radition and thyroid ablation, either by nearly total thyroidectomy or by radioiodine. The different indications for both ablative procedures are discussed. (orig.) [Deutsch] Der Morbus Basedow manifestiert sich klinisch hauptsaechlich als Hyperthyreose und infiltrative Orbitopathie, waehrend Demopathie und Akropathie selten sind. Der Krankheit liegt ein Autoimmunprozess zugrunde, wobei stimuliernde Autoantikoerper gegen den TSH-Rezeptor die Hyperthyreose hervorrufen. Autoantikoerper und T-Lymphozyten gegen primaer thyreoidale Antigene verursachen durch Kreuzreaktion mit aehnlichen Antigenen an den Augenmuskeln und orbitalem Bindegewebe die Orbitopathie. Das therapeutsiche Ziel besteht nicht nur in der Behandlung der Hyperthyreose, sondern vor allem in der Induktion einer immuntoleranten Remission, um die irreversiblen Schaeden am Auge zu minimieren. Die Therapie umfasst Thyreostatika, Glukokortikoide und Orbitaspitzenbestrahlung sowie eine Schilddruesenablation entweder durch fast totale Schilddruesenresektion oder durch Radiojodtherapie. Die Differentialindikationen fuer die beiden ablativen Massnahmen werden eroertert. (orig.)

Contact refusal by children following acrimonious separation: therapeutic approaches with children and parents.

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Dejong, Margaret; Davies, Hilary

2013-04-01

This paper aims to build on the existing literature, by presenting some thoughts based on clinical experience with nine families of children referred for intractable contact refusal with one parent following marital separation. This particular group of high-conflict divorce cases engenders an inordinate amount of frustration both within the courts and therapeutic agencies. We outline here our assessment process and therapeutic strategies, as well as consideration of the role of the wider professional system and the courts. We conclude that whether or not direct contact with the rejected parent is achieved, useful therapeutic work can be carried out to assist children in moving on with their lives.

A measurable impact of a self-practice/self-reflection programme on the therapeutic skills of experienced cognitive-behavioural therapists.

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Davis, Melanie L; Thwaites, Richard; Freeston, Mark H; Bennett-Levy, James

2015-01-01

The need for effective training methods for enhancing cognitive-behavioural therapist competency is not only relevant to new therapists but also to experienced therapists looking to retain and further enhance their skills. Self-practice/self-reflection (SP/SR) is a self-experiential cognitive-behavioural therapy (CBT) training programme, which combines the experience of practicing CBT methods on oneself with structured reflection on the implications of the experience for clinical practice. In order to build on previous qualitative studies of SP/SR, which have mainly focused on trainee CBT therapists, the aim of the current study was to quantify the impact of SP/SR on the therapeutic skills of an experienced cohort of CBT therapists. Fourteen CBT therapists were recruited to participate in an SP/SR programme specifically adapted for experienced therapists. In the context of a quasi-experimental design including multiple baselines within a single-case methodology, therapists provided self-ratings of technical cognitive therapy skill and interpersonal empathic skill at four critical time points: baseline, pre-SP/SR and post-SP/SR and follow-up. Analysis of programme completers (n = 7) indicated that SP/SR enhances both technical skill and interpersonal therapeutic skill. Further intention-to-treat group (n = 14) analyses including both those who left the programme early (n = 3) and those who partially completed the programme (n = 4) added to the robustness of findings with respect to technical cognitive therapy skills but not interpersonal empathic skills. It was concluded that SP/SR, as a training and development programme, could offer an avenue to further therapeutic skill enhancement in already experienced CBT therapists. Copyright © 2014 John Wiley & Sons, Ltd.

Innovations in monoclonal antibody tumor targeting; Diagnostic and therapeutic implications

International Nuclear Information System (INIS)

Schlom, J.

1989-01-01

The detection of carcinoma lesions not identified by conventional radiological and physical examinations remains a major problem in the treatment of many carcinomas. This article reviews potential new modalities and areas of research for carcinoma diagnosis and treatment. A case history is presented

Metastatic nasopharyngeal carcinoma: clinical study and therapeutic results of 95 cases

International Nuclear Information System (INIS)

Khanfir, A.; Frikha, M.; Ghorbel, A.; Drira, M.M.; Karray, H.; Daoud, J.

2006-01-01

Purpose. -- The objective of this retrospective study was to discuss the epidemio-clinical criteria and the therapeutic results of metastatic nasopharyngeal carcinoma. Patients and methods. - The current study concerned 95 patients with histologically proven nasopharyngeal carcinoma who were metastatic at diagnosis or who had developed late metastasis. We reviewed the epidemio-clinical records of all the patients. Patients were treated with chemotherapy (BEC regimen: bleomycin, epirubicin and cisplatin or PBF regimen: bleomycin, 5-fluorouracil and cisplatin) and radiotherapy of pauci metastatic localizations (single or double) or bone metastasis with high risk of compression or fracture ±associated with locoregional radiotherapy for patients who were metastatic at diagnosis. Response was assessed according to the WHO criteria. Overall survival was calculated according to the Kaplan-Meier method. A long-term disease-free survival was defined from 36 months. Results. - There were 34 patients who were metastatic at diagnosis and 61 patients who had developed late metastasis. The mean age was 41.5 years (sex-ratio: 3.1). Bone metastases were the most frequent (83%). Objective and complete response rates were respectively 75% and 70%, and 32% and 16% for BEC and PBF regimens. Twenty-five patients received radiotherapy for pauci metastatic localizations, among whom 19 patients who were metastatic at diagnosis received locoregional irradiation. The overall survival probability was of 15% for three years. Eleven patients were long survivors (extremes: 36 and 134 months). Conclusion. - Therapeutic results were comparable to those reported in other series using platin combination chemotherapy. Radiotherapy of metastasis yielded to long-term survival. (authors)

Therapeutic drug monitoring in pregnancy.

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Matsui, Doreen M

2012-10-01

Therapeutic drug monitoring (TDM) is commonly recommended to optimize drug dosing regimens of various medications. It has been proposed to guide therapy in pregnant women, in whom physiological changes may lead to altered pharmacokinetics resulting in difficulty in predicting the appropriate drug dosage. Ideally, TDM may play a role in enhancing the effectiveness of treatment while minimizing toxicity of both the mother and fetus. Monitoring of drug levels may also be helpful in assessing adherence to prescribed therapy in selected cases. Limitations exist as therapeutic ranges have only been defined for a limited number of drugs and are based on data obtained in nonpregnant patients. TDM has been suggested for anticonvulsants, antidepressants, and antiretroviral drugs, based on pharmacokinetic studies that have shown reduced drug concentrations. However, there is only relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Further studies are required to determine whether implementation of TDM during pregnancy improves outcome and is associated with any benefit beyond that achieved by clinical judgment alone. The cost effectiveness of TDM programs during pregnancy also remains to be examined.

Targeting lipid metabolism of cancer cells: A promising therapeutic strategy for cancer.

Science.gov (United States)

Liu, Qiuping; Luo, Qing; Halim, Alexander; Song, Guanbin

2017-08-10

One of the most important metabolic hallmarks of cancer cells is deregulation of lipid metabolism. In addition, enhancing de novo fatty acid (FA) synthesis, increasing lipid uptake and lipolysis have also been considered as means of FA acquisition in cancer cells. FAs are involved in various aspects of tumourigenesis and tumour progression. Therefore, targeting lipid metabolism is a promising therapeutic strategy for human cancer. Recent studies have shown that reprogramming lipid metabolism plays important roles in providing energy, macromolecules for membrane synthesis, and lipid signals during cancer progression. Moreover, accumulation of lipid droplets in cancer cells acts as a pivotal adaptive response to harmful conditions. Here, we provide a brief review of the crucial roles of FA metabolism in cancer development, and place emphasis on FA origin, utilization and storage in cancer cells. Understanding the regulation of lipid metabolism in cancer cells has important implications for exploring a new therapeutic strategy for management and treatment of cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Toxicological perspectives of inhaled therapeutics and nanoparticles.

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Hayes, Amanda J; Bakand, Shahnaz

2014-07-01

The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges. This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery. Traditionally, inhalation toxicity has been performed on test animals to identify the median lethal concentration of airborne materials. Later maximum tolerable concentration denoted by LC0 has been introduced as a more ethically acceptable end point. More recently, in vitro methods have been developed, allowing the direct exposure of airborne material to cultured human target cells on permeable porous membranes at the air-liquid interface. Modifications of current inhalation therapies, new pulmonary medications for respiratory diseases and implementation of the respiratory tract for systemic drug delivery are providing new challenges when conducting well-designed inhalation toxicology studies. In particular, the area of nanoparticles and nanocarriers is of critical toxicological concern. There is a need to develop toxicological test models, which characterise the toxic response and cellular interaction between inhaled particles and the respiratory system.

Case report

African Journals Online (AJOL)

ebutamanya

28 août 2015 ... (intra-osseous synovial cyst) Clinical and therapeutic aspect: case report. Chir Main. 2009 Feb; 28(1):37-41. PubMed |. Google Scholar. 10. Chantelot C, Laffargue P, Masmejean E, Peltier B, Barouk P,. Fontaine C. Fracture of the scaphoid carpal bone secondary to an intraosseous cyst: apropos of a case.

Clinical case

International Nuclear Information System (INIS)

Garcia Fontes, M

2012-01-01

This presentation is about a case of a patient with liver tumor. The ultrasound scan and Tc technique were used for the diagnosis and treatment. The application of PET - CT FDG contributed to detect peripheral cholangiocarcinoma, the lymph node distance to guide the therapeutic and the recurrence in case of a negative morphological methods.

Traumatic abdominal wall hernia: A case report and literature review

Directory of Open Access Journals (Sweden)

Osama S. Al Beteddini

2016-01-01

Conclusion: Traumatic abdominal wall hernia presents a diagnostic as well as a therapeutic challenge. The therapeutic approach is governed by a multitude of factors emphasizing the need of a patient-tailored, case by case management plan.

Implications of the Incidental Finding of a MYCN Amplified Adrenal Tumor: A Case Report and Update of a Pediatric Disease Diagnosed in Adults

Directory of Open Access Journals (Sweden)

Anna Koumarianou

2013-01-01

Full Text Available MYCN is a well-known oncogene overexpressed in different human malignancies including neuroblastoma, rhabdomyosarcoma, medulloblastoma, astrocytoma, Wilms’ tumor, and small cell lung cancer. While neuroblastoma is one of the most common childhood malignancies, in adults it is extremely rare and its treatment is based on pediatric protocols that take into consideration stage and genotypic features, such as MYCN amplification. Although neuroblastoma therapy has evolved, identification of early stage patients who need chemotherapy continues to pose a therapeutic challenge. The emerging prognostic role of MYCN phenotype of this disease is currently under investigation as it may redefine MYCN amplified subgroups. We describe an unusual case of adult neuroblastoma with MYCN amplification diagnosed incidentally and discuss possible therapeutic dilemmas.

Threaded biliary inside stents are a safe and effective therapeutic option in cases of malignant hilar obstruction.

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Inatomi, Osamu; Bamba, Shigeki; Shioya, Makoto; Mochizuki, Yosuke; Ban, Hiromitsu; Tsujikawa, Tomoyuki; Saito, Yasuharu; Andoh, Akira; Fujiyama, Yoshihide

2013-02-14

Although endoscopic biliary stents have been accepted as part of palliative therapy for cases of malignant hilar obstruction, the optimal endoscopic management regime remains controversial. In this study, we evaluated the safety and efficacy of placing a threaded stent above the sphincter of Oddi (threaded inside plastic stents, threaded PS) and compared the results with those of other stent types. Patients with malignant hilar obstruction, including those requiring biliary drainage for stent occlusion, were selected. Patients received either one of the following endoscopic indwelling stents: threaded PS, conventional plastic stents (conventional PS), or metallic stents (MS). Duration of stent patency and the incident of complication were compared in these patients. Forty-two patients underwent placement of endoscopic indwelling stents (threaded PS = 12, conventional PS = 17, MS = 13). The median duration of threaded PS patency was significantly longer than that of conventional PS patency (142 vs. 32 days; P = 0.04, logrank test). The median duration of threaded PS and MS patency was not significantly different (142 vs. 150 days, P = 0.83). Stent migration did not occur in any group. Among patients who underwent threaded PS placement as a salvage therapy after MS obstruction due to tumor ingrowth, the median duration of MS patency was significantly shorter than that of threaded PS patency (123 vs. 240 days). Threaded PS are safe and effective in cases of malignant hilar obstruction; moreover, it is a suitable therapeutic option not only for initial drainage but also for salvage therapy.

Essential oils, their therapeutic properties, and implication in dentistry: A review.

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Dagli, Namrata; Dagli, Rushabh; Mahmoud, Rasha Said; Baroudi, Kusai

2015-01-01

Antibacterial treatments currently used for treatment cause several side effects, and bacterial resistance to the antibiotics is also increasing. Therefore, there is need to find better alternatives. Essential oils (EOs) have been used for treatment of various ailments since ancient times and have gained popularity over the years. Safety and efficacy of EOs have been proved by several clinical trials. This review gives an overview on the EOs, their uses, and adverse effects. A literature search was performed in the PubMed for clinical trial studies and review articles on EOs published up to February 2015. The search was performed during March 2015. The following keywords were used: "Lavender essential oil," "cinnamon oil," "clove oil," "eucalyptus oil," "peppermint oil," "lemon EOs," and "tea tree oil." Total 70 relevant articles were found in PubMed database. After screening of abstracts, 52 articles were selected to be included in the present review. On the basis of the available information, it can be concluded that EOs have the potential to be developed as preventive or therapeutic agents for various oral diseases, but further clinical trials are required to establish their safety and efficacy.

Molecular and clinical pharmacology of intranasal corticosteroids: clinical and therapeutic implications.

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Derendorf, H; Meltzer, E O

2008-10-01

Intranasal corticosteroids (INSs) are effective treatments for allergic rhinitis, rhinosinusitis, and nasal polyposis. In recent years, increased understanding of corticosteroid and glucocorticoid receptor pharmacology has enabled the development of molecules designed specifically to achieve potent, localized activity with minimal risk of systemic exposure. Pharmacologic potency studies using affinity and other assessments have produced similar rank orders of potency, with the most potent being mometasone furoate, fluticasone propionate, and its modification, fluticasone furoate. The furoate and propionate ester side chains render these agents highly lipophilic, which may facilitate their absorption through nasal mucosa and uptake across phospholipid cell membranes. These compounds demonstrate negligible systemic absorption. Systemic absorption rates are higher among the older corticosteroids (flunisolide, beclomethasone dipropionate, triamcinolone acetonide, and budesonide), which have bioavailabilities in the range of 34-49%. Studies, including 1-year studies with mometasone furoate, fluticasone propionate, and budesonide that evaluated potential systemic effects of INSs in children have generally found no adverse effects on hypothalamic-pituitary-adrenal axis function or growth. Clinical data suggest no significant differences in efficacy between the INSs. Theoretically, newer agents with lower systemic availability may be preferable, and may come closer to the pharmacokinetic/pharmacologic criteria for the ideal therapeutic choice.

Using therapeutic jurisprudence and preventive law to examine disputants' best interests in mediating cases about physicians' practices: a guide for medical regulators.

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Ferris, Lorraine E

2004-01-01

Therapeutic jurisprudence (TJ) and preventive law (PL) are used as two theoretical perspectives from which to examine the best interests of parties in mediation because of a dispute about a physician's practice. The focus is mediation provided by and/or for the medical regulator. The paper reviews the literature on TJ and PL, and their relationship to mediation, and demonstrates how medical regulators could benefit by working within a framework reflecting both these perspectives providing it does not involve an egregious matter. A TJ and PL framework would be of particular value in identifying cases for mediation and in evaluating resolutions to mediated disputes.

Therapeutic communication in nursing students: A Walker & Avant concept analysis

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Abdolrahimi, Mahbobeh; Ghiyasvandian, Shahrzad; Zakerimoghadam, Masoumeh; Ebadi, Abbas

2017-01-01

Background and aim Therapeutic communication, the fundamental component of nursing, is a complex concept. Furthermore, the poor encounters between nursing student and patient demonstrate the necessity of instruction regarding therapeutic communication. The aim of this study was to define and clarify this important concept for including this subject in the nursing curriculum with more emphasis. Methods A literature search was conducted using keywords such as “nursing student”, “patient” and “therapeutic communication” and Persian-equivalent words in Persian databases (including Magiran and Medlib) and English databases (including PubMed, ScienceDirect, Scopus and ProQuest) without time limitation. After extracting concept definitions and determining characteristic features, therapeutic communication in nursing students was defined. Then, sample cases, antecedents, consequences and empirical referents of concept were determined. Results After assessing 30 articles, therapeutic communication defining attributes were as follows: “an important means in building interpersonal relationships”, “a process of information transmission”, “an important clinical competency”, “a structure with two different sections” and “a significant tool in patient centered care”. Furthermore, theoretical and clinical education and receiving educators’ feedback regarding therapeutic communication were considered as antecedents of the concept. Improving physical and psychological health status of patient as well as professional development of nursing students were identified as consequences of the concept. Conclusion Nursing instructors can use these results in order to teach and evaluate therapeutic communication in nursing students and train qualified nurses. Also, nursing students may apply the results to improve the quality of their interactions with patients, perform their various duties and meet patients’ diverse needs. PMID:28979730

An analysis of policies for cotrimoxazole, amoxicillin and azithromycin use in Namibia's public sector: Findings and therapeutic implications.

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Kibuule, Dan; Mubita, Mwangana; Naikaku, Ester; Kalemeera, Francis; Godman, Brian B; Sagwa, Evans

2017-02-01

Despite Namibia's robust medicine use systems and policies, antibiotic use indicators remain suboptimal. Recent medicine use surveys rank cotrimoxazole, amoxicillin and azithromycin (CAA) among the most used medicines. However, there is rising resistance to CAA (55.9%-96.7%). Unfortunately, to date, there have been limited studies evaluating policies to improve antibiotic use in Namibia. To evaluate public sector pharmaceutical policies and guidelines influencing the therapeutic use of CAA antibiotics in Namibia. Evaluate Namibia's pharmaceutical policies and guidelines for CAA use through quantitative text analysis. The main outcome variables were the existence of antibiotic policies, therapeutic indications per antibiotic and the type/level of healthcare facility allowed to use the antibiotic. Policies for antibiotic use were limited, with only the draft Namibia Medicines Policy having a statement on antibiotic use. Several essential antibiotics had no therapeutic indications mentioned in the guidelines. Twenty-nine antibiotics were listed for 69 therapeutic indications; CAA (49.3%) antibiotics and ATC J01C/J01D (48%) having the highest indications per antibiotic. For CAA antibiotics, this suggested use was mainly for acute respiratory infections (n=22, 37.2%). Published policies (58.6%-17/29) recommended antibiotics for use at the primary healthcare (PHC) level, with CAA antibiotics recommended mostly for respiratory tract infections and genitourinary infections. Policy and guidelines for antibiotic use in Namibia are not comprehensive and are skewed towards PHCs. Existing policies promote the wide use of CAA antibiotics, which may inadvertently result in their inappropriate use enhancing resistance rates. This calls for the development of more comprehensive antibiotic guidelines and essential medicine lists in tandem with local antimicrobial resistance patterns. In addition, educational initiatives among all key stakeholder groups. © 2017 John Wiley & Sons Ltd.

Smoking, nicotine and psychiatric disorders: evidence for therapeutic role, controversies and implications for future research.

Science.gov (United States)

Dursun, S M; Kutcher, S

1999-02-01

Researchers interested in investigating the possible therapeutic effects and the mechanisms of action of nicotine in neuropsychiatric disorders face a social-scientific-ethical dilemma. This dilemma comprises three components: (1) the known addictive potential of nicotine makes careful evaluation of the therapeutic potential of this compound socially unattractive; (2) the potential misuse of scientifically determined data by the tobacco 'lobby' creates ethical concerns; and (3) the possible confusion between the differential effects of nicotine in human smokers versus non-smokers creates difficulties in study designs in voluntary human subjects. Therefore, it is imperative that, at the onset of this review, the authors stress that they do not advocate cigarette-smoking as a route of nicotine intake under any circumstances on the basis that controlled dosing of nicotine may be of potential benefit in some neuropsychiatric disorders. In this article, we review the psychopharmacology of nicotine and its effects in a variety of neuropsychiatric disorders including schizophrenia, depression, anxiety and Tourette's syndrome. Possible mechanisms of action of nicotine directly or indirectly via its interaction with other neurotransmitter systems (i.e. serotonin, dopamine and noradrenaline) in relation to its potential role in these disorders are discussed. It is postulated that new drugs may need to be developed that selectively interact with nicotinic receptors without addiction potential.

Experiences of women with stress-related ill health in a therapeutic gardening program.

Science.gov (United States)

Eriksson, Therese; Westerberg, Yvonne; Jonsson, Hans

2011-12-01

Stress-related ill health, e.g. burnout, is of great concern worldwide. Effective rehabilitation programs need to be developed and their therapeutic aspects understood. To explore and describe how women with stress-related ill health who are on sick leave experience the rehabilitation process in a therapeutic garden and how these experiences connect to their everyday lives. This longitudinal study used methods from grounded theory. Five women completed three semi-structured interviews at three weekly intervals during rehabilitation and one interview three months after. Data were analyzed using a constant comparative approach. A secure environment facilitated engagement in activities that provided feelings of enjoyment. These experiences inspired participants to add enjoyable activities in their everyday lives, contributing to occupational balance, despite worries of not be able to continue performing enjoyable activities. Implications. Effective rehabilitation programs need to focus on enjoyable activities in a protective environment to support achievement of occupational balance.

Ebola virus outbreak, updates on current therapeutic strategies.

Science.gov (United States)

Elshabrawy, Hatem A; Erickson, Timothy B; Prabhakar, Bellur S

2015-07-01

Filoviruses are enveloped negative-sense single-stranded RNA viruses, which include Ebola and Marburg viruses, known to cause hemorrhagic fever in humans with a case fatality of up to 90%. There have been several Ebola virus outbreaks since the first outbreak in the Democratic Republic of Congo in 1976 of which, the recent 2013-2015 epidemic in Guinea, Liberia, and Sierra Leone is the largest in recorded history. Within a few months of the start of the outbreak in December 2013, thousands of infected cases were reported with a significant number of deaths. As of March 2015, according to the Centers for Disease Control and Prevention, there have been nearly 25,000 suspected cases, with 15,000 confirmed by laboratory testing, and over 10,000 deaths. The large number of cases and the high mortality rate, combined with the lack of effective Food and Drug Administration-approved treatments, necessitate the development of potent and safe therapeutic measures to combat the current and future outbreaks. Since the beginning of the outbreak, there have been considerable efforts to develop and characterize protective measures including vaccines and antiviral small molecules, and some have proven effective in vitro and in animal models. Most recently, a cocktail of monoclonal antibodies has been shown to be highly effective in protecting non-human primates from Ebola virus infection. In this review, we will discuss what is known about the nature of the virus, phylogenetic classification, genomic organization and replication, disease transmission, and viral entry and highlight the current approaches and efforts, in the development of therapeutics, to control the outbreak. Copyright © 2015 John Wiley & Sons, Ltd.

THERAPEUTIC EFFECTS OF ELECTROACUPUNCTURE PLUS POINT-PENETRATION FOR CHRONIC ANKLE JOINT SPRAIN

Institute of Scientific and Technical Information of China (English)

ZHAO Yi-zao

2005-01-01

Objective: To observe clinical therapeutic effects of electroacupuncture plus point-penetration for chronic ankle joint sprain. Methods: 76 patients were randomly divided into treatment group (n=43) and control group (n=33).In teatment group, penetration needling from Qiuxu (丘墟 GB 40) to Zhaohai (照海 KI 6) was performed, combined with electrical stimulation for 30 min. Patients of control group were ordered to take Antinfan (50 mg,b.I.d.),supplemented with local external application of Votalin cream (b.I.d.).After 14 treatments (two courses), the therapeutic effect was assessed. Results: Following two courses of treatment, of the 43 cases and 33 cases in treatment and control groups,33 (76.7%) and 15 (45.5%) were cured, 4 (9.3%) and 7 (21.2%) had marked improvement in their symptoms, 3 (7.0%) and 2 (6.1%) had improvement, and 3 (7.0%) and 9(27.3%) failed, with the effective rates being 93.0% and 72.7% respectively. The therapeutic effect of treatment group was significantly superior to that of control group (P<0.05). Conclusion: Penetrative needling plus EA is significantly superior to medication in relieving chronic ankle spain patient's clinical symptoms and signs.

ER Stress: A Therapeutic Target in Rheumatoid Arthritis?

Science.gov (United States)

Rahmati, Marveh; Moosavi, Mohammad Amin; McDermott, Michael F

2018-04-22

Diverse physiological and pathological conditions that impact on protein folding of the endoplasmic reticulum (ER) cause ER stress. The unfolded protein response (UPR) and the ER-associated degradation (ERAD) pathway are activated to cope with ER stress. In rheumatoid arthritis (RA), inflammation and ER stress work in parallel by driving inflammatory cells to release cytokines that induce chronic ER stress pathways. This chronic ER stress may contribute to the pathogenesis of RA through synoviocyte proliferation and proinflammatory cytokine production. Therefore, ER stress pathways and their constituent elements are attractive targets for RA drug development. In this review, we integrate current knowledge of the contribution of ER stress to the overall pathogenesis of RA, and suggest some therapeutic implications of these discoveries. Copyright © 2018 Elsevier Ltd. All rights reserved.

Infrapopliteal calcification patterns in critical limb ischemia: diagnostic, pathologic and therapeutic implications in the search for the endovascular holy grail.

Science.gov (United States)

Mustapha, Jihad A; Diaz-Sandoval, Larry J; Saab, Fadi

2017-06-01

Critical limb ischemia (CLI) represents the terminal stage of peripheral arterial disease (PAD) and is characterized by multilevel and multivessel disease. Amongst patients with infrainguinal disease, approximately one third have predominantly isolated infrapopliteal disease and the remaining two thirds, a combination of femoropopliteal and infrapopliteal disease. Isolated infrapopliteal disease is mainly seen in the elderly, diabetic, or dialysis-dependent patients. These patients have higher risk of amputation and shorter amputation-free survival. Infrapopliteal disease presents with either complex high-grade calcified tandem lesions in multiple vessels or with long chronic total occlusion (CTO) segments with plaques characterized by higher calcium and lower fibro-fatty content than the inflow vessels, as arterial calcium deposition increases as we progress distally in the arterial tree. Vascular calcification occurs in both intima and media. Intimal calcification leads to development of calcified atheroma and occlusive lesions. Medial calcification leads to stiffening and decrease in arterial wall elasticity and compliance leading to atherosclerosis, reduced perfusion, and PAD, increasing cardiovascular mortality among patients with end-stage renal disease. This article attempts to review the implications of the diverse pathologic patterns of calcium distribution in infrapopliteal vessels of CLI patients, on the diagnostic modalities, technological developments, and the evolution of therapeutic approaches to improve outcomes among these patients. A critical analysis of the currently available data is provided, pointing to the surprising omission on the role of calcium on outcomes, and future directions are discussed. Is infrapopliteal calcium a roadblock or the avenue towards new paths? Necessity remains the mother of invention.

Environmental implications of electricity purchase from independent power producers: a case study from Thailand

International Nuclear Information System (INIS)

Rabin Shrestha; Ram M Shrestha

2003-01-01

This paper analyses the effect on the environment of electricity purchase from independent power producers (IPPs) in the case of Thailand. The environmental implication is evaluated in terms of the net change in emission of air pollutants with electricity purchase from IPPs by a utility. The main finding of the study is that electricity purchase from a non-dispatchable IPP plant based on coal-fired generation would increase the net emissions compared with that without the purchase from IPPs. The study also shows that the lower plant factor of the IPP plant would also increase the emission of air pollutants. Furthermore, with non-dispatchable IPP plants, the total emission of air pollutants would increase, whereas with dispatchable IPP plants the total emission would decrease with the level of electricity purchases. (author)

Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value?

Science.gov (United States)

Allen, Patricia J.

2012-01-01

Athletes, body builders, and military personnel use dietary creatine as an ergogenic aid to boost physical performance in sports involving short bursts of high-intensity muscle activity. Lesser known is the essential role creatine, a natural regulator of energy homeostasis, plays in brain function and development. Creatine supplementation has shown promise as a safe, effective, and tolerable adjunct to medication for the treatment of brain-related disorders linked with dysfunctional energy metabolism, such as Huntington’s Disease and Parkinson’s Disease. Impairments in creatine metabolism have also been implicated in the pathogenesis of psychiatric disorders, leaving clinicians, researchers and patients alike wondering if dietary creatine has therapeutic value for treating mental illness. The present review summarizes the neurobiology of the creatine-phosphocreatine circuit and its relation to psychological stress, schizophrenia, mood and anxiety disorders. While present knowledge of the role of creatine in cognitive and emotional processing is in its infancy, further research on this endogenous metabolite has the potential to advance our understanding of the biological bases of psychopathology and improve current therapeutic strategies. PMID:22465051

Therapeutic Approaches Using Riboflavin in Mitochondrial Energy Metabolism Disorders.

Science.gov (United States)

Henriques, Bárbara J; Lucas, Tânia G; Gomes, Cláudio M

2016-01-01

Riboflavin, or vitamin B2, plays an important role in the cell as biological precursor of FAD and FMN, two important flavin cofactors which are essential for the structure and function of flavoproteins. Riboflavin has been used in therapeutic approaches of various inborn errors of metabolism, notably in metabolic disorders resulting either from defects in proteins involved in riboflavin metabolism and transport or from defects in flavoenzymes. The scope of this review is to provide an updated perspective of clinical cases in which riboflavin was used as a potential therapeutic agent in disorders affecting mitochondrial energy metabolism. In particular, we discuss available mechanistic insights on the role of riboflavin as a pharmacological chaperone for the recovery of misfolded metabolic flavoenzymes.

A case of metronidazole-resistant Trichomonas vaginalis in pregnancy.

Science.gov (United States)

Forbes, Georgina L; Drayton, Rachel; Forbes, Gavin D

2016-09-01

Trichomonas vaginalis is a sexually transmitted protozoan infection resulting in vulvo-vaginitis and altered vaginal discharge in symptomatic women. Trichomoniasis has been implicated in causing adverse pregnancy outcomes such as low birth weight and pre-term labour. Metronidazole is the recommended first-line treatment for trichomonal infection. Other nitroimidazoles, such as tinidazole, are used as alternative regimens with similar activity but at a greater expense. Treatment failure usually represents patient non-compliance or re-infection, although metronidazole resistance has previously been documented. Antimicrobial susceptibility testing for T. vaginalis is currently not available in the UK. Patients with disease unresponsive to first-line treatments pose a major challenge, as therapeutic options are limited. We present the case of a patient with presumed resistant infection during pregnancy, and the additional treatment issues that this presented. © The Author(s) 2015.

Immunological mechanism underlying the immune response to tecombinant human protein therapeutics

NARCIS (Netherlands)

Sauerborn, M.S.; Brinks, V.; Jiskoot, W.; Schellekens, H.

2010-01-01

Recombinant human (rhu) protein therapeutics are powerful tools to treat several severe diseases such as multiple sclerosis and diabetes mellitus, among others. A major drawback of these proteins is the production of anti-drug antibodies (ADAs). In some cases, these ADAs have neutralizing capacity

Therapeutic vaccine for acute and chronic motor neuron diseases: implications for amyotrophic lateral sclerosis.

Science.gov (United States)

Angelov, D N; Waibel, S; Guntinas-Lichius, O; Lenzen, M; Neiss, W F; Tomov, T L; Yoles, E; Kipnis, J; Schori, H; Reuter, A; Ludolph, A; Schwartz, M

2003-04-15

Therapeutic vaccination with Copaxone (glatiramer acetate, Cop-1) protects motor neurons against acute and chronic degenerative conditions. In acute degeneration after facial nerve axotomy, the number of surviving motor neurons was almost two times higher in Cop-1-vaccinated mice than in nonvaccinated mice, or in mice injected with PBS emulsified in complete Freund's adjuvant (P amyotrophic lateral sclerosis, Cop-1 vaccination prolonged life span compared to untreated matched controls, from 211 +/- 7 days (n = 15) to 263 +/- 8 days (n = 14; P sclerosis. The protocol for non-autoimmune neurodegenerative diseases such as amyotrophic lateral sclerosis, remains to be established by future studies.

[Therapeutic drug monitoring of three antiepileptic drugs - Back on twenty years of experience].

Science.gov (United States)

Serragui, Samira; Zalagh, Fatima; Tanani, Driss Soussi; Ouammi, Lahcen; Moussa, Latifa Ait; Badrane, Narjis; Bencheikh, Rachida Soulaymani

2016-01-01

The therapeutic drug monitoring (TDM) of antiepileptic drugs is a tool widely used in the management of epilepsy. In Morocco, this monitoring is carried out by the Centre Anti Poison et Pharmacovigilance (CAPM) since April 1995. This is a retrospective study spanning 20 years. It concerns the therapeutic drug monitoring of Phenobarbital (PB) of carbamazepine (CBZ) and valproic acid (VPA). Therapeutic drug monitoring of the 3 antiepileptic drugs represent 58.85% of all applications received by the CAPM. The dosage of PB was ranked first followed by that of CBZ and finally by the VPA. Weak demand for therapeutic drug monitoring in Morocco could be explained by the low number of neurologists in addition to social factors. With its affordable price by patients, PB is the most prescribed antiepileptic drug in our country, which explains the high demand for its dosage. As for the therapeutic drug monitoring of the antiepileptic drug, they were mainly related to age, the occurrence of adverse effects, the association antiepileptic drugs or in the case of verification of patient compliance. Efforts are required for promoting the interests of therapeutic drug monitoring of antiepileptic drug in the management of epilepsy in Morocco.

Dry eye syndrome. Etiological and therapeutic aspects.

Science.gov (United States)

Apostol, Silvia; Filip, M; Dragne, Carmen; Filip, A

2003-01-01

"Dry eye syndrome" is a common disorder of the tear film that results from inadequate tear production, excessive tear evaporation or abnormality in mucin or lipid components of the tear film. A number of 53 patients suffering from dry eye syndrome were followed up for a period of 18 months. The study group was heterogeneous, including a lot of conditions accompanied by dry eye syndrome: Syogren's syndrome, lupus erythematous, ocular rosacea, patients with systemic treatments with antidepressants, betablockers, diuretics, oral contraceptives, glaucomatous patients with topical beta-blockers, postmenopausal women, aging people, computer users and long-term contact lens wearers. The therapeutical options were dictated by the severity of the syndrome: substitution therapy, treatment of the underlying eyelid diseases, modifying of the environmental conditions and treatment of the complications in the most severe cases. The new pathological approach is innovative and it may provide a real therapeutical measure for this condition: topical A Cyclosporine and androgen drops.

[Therapeutic strategy for different types of epicanthus].

Science.gov (United States)

Gaofeng, Li; Jun, Tan; Zihan, Wu; Wei, Ding; Huawei, Ouyang; Fan, Zhang; Mingcan, Luo

2015-11-01

To explore the reasonable therapeutic strategy for different types of epicanthus. Patients with epicanthus were classificated according to the shape, extent and inner canthal distance and treated with different methods appropriately. Modified asymmetric Z plasty with two curve method was used in lower eyelid type epicanthus, inner canthus type epicanthus and severe upper eyelid type epicanthus. Moderate upper epicanthus underwent '-' shape method. Mild Upper epicanthus in two conditions which underwent nasal augumentation and double eyelid formation with normal inner canthal distance need no correction surgery. The other mild epicanthus underwent '-' shape method. A total of 66 cases underwent the classification and the appropriate treatment. All wounds healed well. During 3 to 12 months follow-up period, all epicanthus were corrected completely with natural contour and unconspicuous scars. All patients were satisfied with the results. Classification of epicanthus hosed on the shape, extent and inner canthal distance and correction with appropriate methods is a reasonable therapeutic strategy.

DISC1 pathway in brain development: exploring therapeutic targets for major psychiatric disorders

Directory of Open Access Journals (Sweden)

Atsushi eKamiya

2012-03-01

Full Text Available Genetic risk factors for major psychiatric disorders play key roles in neurodevelopment. Thus, exploring the molecular pathways of risk genes is important not only for understanding the molecular mechanisms underlying brain development, but also to decipher how genetic disturbances affect brain maturation and functioning relevant to major mental illnesses. During the last decade, there has been significant progress in determining the mechanisms whereby risk genes impact brain development. Nonetheless, given that the majority of psychiatric disorders have etiological complexities encompassing multiple risk genes and environmental factors, the biological mechanisms of these diseases remain poorly understood. How can we move forward in our research for discovery of the biological markers and novel therapeutic targets for major mental disorders? Here we review recent progress in the neurobiology of Disrupted in schizophrenia 1 (DISC1, a major risk gene for major mental disorders, with a particular focus on its roles in cerebral cortex development. Convergent findings implicate DISC1 as part of a large, multi-step pathway implicated in various cellular processes and signal transduction. We discuss links between the DISC1 pathway and environmental factors, such as immune/inflammatory responses, which may suggest novel therapeutic targets. Existing treatments for major mental disorders are hampered by a limited number of pharmacological targets. Consequently, elucidation of the DISC1 pathway, and its association with neuropsychiatric disorders, may offer hope for novel treatment interventions.

French healthcare professionals' perceived barriers to and motivation for therapeutic patient education: A qualitative study.

Science.gov (United States)

Lelorain, Sophie; Bachelet, Adeline; Bertin, Nicole; Bourgoin, Maryline

2017-09-01

Therapeutic patient education is effective for various patient outcomes; however, healthcare professionals sometimes lack the motivation to carry out patient education. Surprisingly, this issue has rarely been addressed in research. Therefore, this study explores healthcare professionals' perceived barriers to and motivation for therapeutic patient education. Healthcare professionals, mainly nurses, working in different French hospitals were interviewed. Thematic content analysis was performed. Findings included a lack of skills, knowledge, and disillusionment of the effectiveness of therapeutic patient education were features of a demotivated attitude. In contrast, a positive attitude was observed when therapeutic patient education met a need to work differently and more effectively. A key factor motivating professionals was the integration of therapeutic patient education in routine care within a multidisciplinary team. To keep healthcare professionals motivated, managers should ensure that therapeutic patient education is implemented in accordance with its core principles: a patient-centered approach within a trained multidisciplinary team. In the latter case, therapeutic patient education is viewed as an efficient and rewarding way to work with patients, which significantly motivates healthcare professionals. © 2017 John Wiley & Sons Australia, Ltd.

Alzheimer disease therapeutics: focus on the disease and not just plaques and tangles.

Science.gov (United States)

Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

2014-04-15

The bulk of AD research during the last 25 years has been Aβ-centric based on a strong faith in the Amyloid Cascade Hypothesis which is not supported by the data on humans. To date, Aβ-based therapeutic clinical trials on sporadic cases of AD have been negative. Although most likely the major reason for the failure is that Aβ is not an effective therapeutic target for sporadic AD, initiation of the treatment at mild to moderate stages of the disease is blamed as too late to be effective. Clinical trials on presymptomatic familial AD cases have been initiated with the logic that Aβ is a trigger of the disease and hence initiation of the Aβ immunotherapies several years before any clinical symptoms would be effective. There is an urgent need to explore targets other than Aβ. There is now increasing interest in inhibiting tau pathology, which does have a far more compelling rationale than Aβ. AD is multifactorial and over 99% of the cases are the sporadic form of the disease. Understanding of the various etiopathogenic mechanisms of sporadic AD and generation of the disease-relevant animal models are required to develop rational therapeutic targets and therapies. Treatment of AD will require both inhibition of neurodegeneration and regeneration of the brain. Copyright © 2014 Elsevier Inc. All rights reserved.

Design and Pharmacokinetic Characterization of Novel Antibody Formats for Ocular Therapeutics.

Science.gov (United States)

Gadkar, Kapil; Pastuskovas, Cinthia V; Le Couter, Jennifer E; Elliott, J Michael; Zhang, Jianhuan; Lee, Chingwei V; Sanowar, Sarah; Fuh, Germaine; Kim, Hok Seon; Lombana, T Noelle; Spiess, Christoph; Nakamura, Makia; Hass, Phil; Shatz, Whitney; Meng, Y Gloria; Scheer, Justin M

2015-08-01

To design and select the next generation of ocular therapeutics, we performed a comprehensive ocular and systemic pharmacokinetic (PK) analysis of a variety of antibodies and antibody fragments, including a novel-designed bispecific antibody. Molecules were administrated via intravitreal (IVT) or intravenous (IV) injections in rabbits, and antibody concentrations in each tissue were determined by ELISA. A novel mathematical model was developed to quantitate the structure-PK relationship. After IVT injection, differences in vitreal half-life observed across all molecules ranged between 3.2 and 5.2 days. Modification or elimination of the fragment crystallizable (Fc) region reduced serum half-life from 9 days for the IgG to 5 days for the neonatal Fc receptor (FcRn) null mAb, to 3.1 to 3.4 days for the other formats. The F(ab')2 was the optimal format for ocular therapeutics with comparable vitreal half-life to full-length antibodies, but with minimized systemic exposure. Concomitantly, the consistency among mathematical model predictions and observed data validated the model for future PK predictions. In addition, we showed a novel design to develop bispecific antibodies, here with activity targeting multiple angiogenesis pathways. We demonstrated that protein molecular weight and Fc region do not play a critical role in ocular PK, as they do systemically. Moreover, the mathematical model supports the selection of the "ideal therapeutic" by predicting ocular and systemic PK of any antibody format for any dose regimen. These findings have important implications for the design and selection of ocular therapeutics according to treatment needs, such as maximizing ocular half-life and minimizing systemic exposure.

Intra-firm knowledge transfer-a qualitative case study of knowledge transfer and its implications in a soft service firm

OpenAIRE

Zheleva, Denitsa; Viklund, Alexandra

2014-01-01

The following case study aims to explore the knowledge transfer and its implications in the context of a soft service firm. The complexity of knowledge itself and the knowledge transfer process in service firms brings new challenges. The phenomenon was investigated by the application of grounded theory. Interviews were conducted with employees at a company present in the Quick Service Restaurant segment. It resulted in several findings that were not reported by previous literature. Firstly, w...

Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It's Been ….

Science.gov (United States)

Baron, Eric P

2015-06-01

The use of cannabis, or marijuana, for medicinal purposes is deeply rooted though history, dating back to ancient times. It once held a prominent position in the history of medicine, recommended by many eminent physicians for numerous diseases, particularly headache and migraine. Through the decades, this plant has taken a fascinating journey from a legal and frequently prescribed status to illegal, driven by political and social factors rather than by science. However, with an abundance of growing support for its multitude of medicinal uses, the misguided stigma of cannabis is fading, and there has been a dramatic push for legalizing medicinal cannabis and research. Almost half of the United States has now legalized medicinal cannabis, several states have legalized recreational use, and others have legalized cannabidiol-only use, which is one of many therapeutic cannabinoids extracted from cannabis. Physicians need to be educated on the history, pharmacology, clinical indications, and proper clinical use of cannabis, as patients will inevitably inquire about it for many diseases, including chronic pain and headache disorders for which there is some intriguing supportive evidence. To review the history of medicinal cannabis use, discuss the pharmacology and physiology of the endocannabinoid system and cannabis-derived cannabinoids, perform a comprehensive literature review of the clinical uses of medicinal cannabis and cannabinoids with a focus on migraine and other headache disorders, and outline general clinical practice guidelines. The literature suggests that the medicinal use of cannabis may have a therapeutic role for a multitude of diseases, particularly chronic pain disorders including headache. Supporting literature suggests a role for medicinal cannabis and cannabinoids in several types of headache disorders including migraine and cluster headache, although it is primarily limited to case based, anecdotal, or laboratory-based scientific research. Cannabis

Strategies of Echinococcus species responses to immune attacks: implications for therapeutic tool development.

Science.gov (United States)

Zheng, Yadong

2013-11-01

Echinococcus species have been studied as a model to investigate parasite-host interactions. Echinococcus spp. can actively communicate dynamically with a host to facilitate infection, growth and proliferation partially via secretion of molecules, especially in terms of harmonization of host immune attacks. This review systematically outlines our current knowledge of how the Echinococcus species have evolved to adapt to their host's microenvironment. This understanding of parasite-host interplay has implications in profound appreciation of parasite plasticity and is informative in designing novel and effective tools including vaccines and drugs for the treatment of echinococcosis and other diseases. © 2013.

[Therapeutic effects of the integrated acupuncture and Chinese herbal medicine on reflux esophagitis].

Science.gov (United States)

Zhang, Wan; Li, Bolin; Sun, Jianhui; Wang, Zhikun; Zhang, Nana; Shi, Fang; Pei, Lin

2017-07-12

To compare the differences in the clinical therapeutic effects on reflux esophagitis among the combined therapy of huazhuo jiedu jiangni decoction (the decoction for resolving the turbid, detoxification and reducing the pathologic upward qi in short) and acupuncture, omeprazole and Chinese herbal medicine. Ninety patients were randomized into 3 groups, 4 cases of them were dropped off. Finally, there were 29 cases in the combined therapy group with acupuncture and the decoction, 29 cases in the western medication group and 28 cases in the Chinese herbal medicine group in the statistical analysis. In the combined therapy group with acupuncture and the decoction, the decoction was prescribed recurrence rate. The therapeutic effects are better than the simple application of either Chinese herbal medicine or omeprazole. for oral administration. Additionally, acupuncture was applied to Neiguan (PC 6), Zusanli (ST 36), Zhongwan (CV 12), Ganshu (BL 18), Danshu (BL 19) and Taichong (LR 3). The decoction was applied one dose a day and acupuncture was once a day. In the western medication group, omeprazole capsules, 20 mg were prescribed for oral administration, twice a day. In the Chinese herbal medicine group, the decoction was simply applied. The treatment was 8 weeks in the 3 groups and the follow-up visit was 6 months. The score of reflux disorder questionnaire (RDQ) and the changes in esophageal mucosa under gastroscope were observed before and after treatment; the clinical therapeutic effects and recurrence rate were evaluated in the 3 groups. In 4 and 8 weeks of treatment, RDQ scores in the 3 groups were all reduced as compared with those before treatment (all P herbal medicine was lower than that in the western medication group ( P herbal medicine was lower than those in the western medication group and the Chinese herbal medicine group (both P herbal medicine group (all P <0.05). The combined therapy of huazhuo jiedu jiangni decoction and acupuncture achieve the

Influence of perfusion and ventilation scans on therapeutic decision making and outcome in cases of possible embolism

International Nuclear Information System (INIS)

Mercandetti, A.J.; Kipper, M.S.; Moser, K.M.

1985-01-01

The authors examined the influence of perfusion (Q) and ventilation (V) scans on therapeutic decision making and outcome among 229 patients referred for lung scans because embolism was suggested and found that specific V/Q scan patterns strongly influenced postscan decisions regarding initiation, maintenance or cessation of heparin therapy. These therapeutic decisions bore a relationship to outcome (recurrences and death) and disclosed decision-making deficits that need remedy by future investigational and educational efforts. 25 references, 5 tables

DEPDC5 as a potential therapeutic target for epilepsy.

Science.gov (United States)

Myers, Kenneth A; Scheffer, Ingrid E

2017-06-01

Dishevelled, Egl-10 and Pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a protein subunit of the GTPase-activating proteins towards Rags 1 (GATOR1) complex. GATOR1 is a recently identified modulator of mechanistic target of rapamycin (mTOR) activity. mTOR is a key regulator of cell proliferation and metabolism; disruption of the mTOR pathway is implicated in focal epilepsy, both acquired and genetic. Tuberous sclerosis is the prototypic mTOR genetic syndrome with epilepsy, however GATOR1 gene mutations have recently been shown to cause lesional and non-lesional focal epilepsy. Areas covered: This review summarizes the mTOR pathway, including regulators and downstream effectors, emphasizing recent developments in the understanding of the complex role of the GATOR1 complex. We review the epilepsy types associated with mTOR overactivity, including tuberous sclerosis, polyhydramnios megalencephaly symptomatic epilepsy, cortical dysplasia, non-lesional focal epilepsy and post-traumatic epilepsy. Currently available mTOR inhibitors are discussed, primarily rapamycin analogs and ATP competitive mTOR inhibitors. Expert opinion: DEPDC5 is an attractive therapeutic target in focal epilepsy, as effects of DEPDC5 agonists would likely be anti-epileptogenic and more selective than currently available mTOR inhibitors. Therapeutic effects might be synergistic with certain existing dietary therapies, including the ketogenic diet.

The therapeutic short story as a way from resilience. A first approach.

Directory of Open Access Journals (Sweden)

Mónica Bruder

2015-09-01

Full Text Available Starting from the “therapeutic short story” tool, we wonder its possible relationship with the concept of “resiliencia” and the level of influence. Theory is complemented by an experimental study and a model case of example. 

Recent advances in (therapeutic protein drug development [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

H.A. Daniel Lagassé

2017-02-01

Full Text Available Therapeutic protein drugs are an important class of medicines serving patients most in need of novel therapies. Recently approved recombinant protein therapeutics have been developed to treat a wide variety of clinical indications, including cancers, autoimmunity/inflammation, exposure to infectious agents, and genetic disorders. The latest advances in protein-engineering technologies have allowed drug developers and manufacturers to fine-tune and exploit desirable functional characteristics of proteins of interest while maintaining (and in some cases enhancing product safety or efficacy or both. In this review, we highlight the emerging trends and approaches in protein drug development by using examples of therapeutic proteins approved by the U.S. Food and Drug Administration over the previous five years (2011–2016, namely January 1, 2011, through August 31, 2016.

Therapeutic value of selective salpingography for infertile women with patent fallopian tubes: the impact on pregnancy rate.

Science.gov (United States)

Kamiyama, S; Miyagi, H; Kanazawa, K

2000-01-01

To determine the therapeutic value of selective salpingography (SSG) for infertile women with patent fallopian tubes. Retrospective, case-control analysis. University Hospital, infertility clinic. Infertile cases with patent tubes documented by hysterosalpingography (HSG) or by HSG followed by laparoscopic examination (n = 80). Hysteroscopic SSG. Patency rate of tubes by SSG. Pregnancy rate following SSG. Eighty cases were divided into the study group (SSG performed, 37 cases) and the case-control group (SSG not performed, 43 cases). Successful SSG of at least one tube was obtained in all of 37 cases (100%) in whom SSG was attempted. A patency rate of 95.9% was documented in the 73 cannulated tubes of these cases. The total subsequent pregnancy rate (48.6%) within 12 months of follow-up after SSG was significantly higher than that (11.6%) obtained in the control group (p women, either as a sole therapeutic approach or in association with other methods of assisted reproductive technology, even if their fallopian tubes are shown to be patent by HSG. Copyright 2000 S. Karger AG, Basel

Alterations in polyadenylation and its implications for endocrine disease

Directory of Open Access Journals (Sweden)

Anders eRehfeld

2013-05-01

Full Text Available IntroductionPolyadenylation is the process in which the pre-mRNA is cleaved at the poly(A site and a poly(A tail is added - a process necessary for normal mRNA formation. Genes with multiple poly(A sites can undergo alternative polyadenylation, producing distinct mRNA isoforms with different 3’ untranslated regions (3’ UTRs and in some cases different coding regions. Two thirds of all human genes undergo alternative polyadenylation. The efficiency of the polyadenylation process regulates gene expression and alternative polyadenylation plays an important part in post-transcriptional regulation, as the 3’ UTR contains various cis-elements associated with post-transcriptional regulation, such as target sites for microRNAs and RNA-binding proteins.Implications of alterations in polyadenylation for endocrine diseaseAlterations in polyadenylation have been found to be causative of neonatal diabetes and IPEX (immune dysfunction, polyendocrinopathy, enteropathy, X-linked and to be associated with type I and II diabetes, pre-eclampsia, fragile X-associated premature ovarian insufficiency, ectopic Cushing syndrome and many cancer diseases, including several types of endocrine tumor diseases.PerspectivesRecent developments in high-throughput sequencing have made it possible to characterize polyadenylation genome-wide. Antisense elements inhibiting or enhancing specific poly(A site usage can induce desired alterations in polyadenylation, and thus hold the promise of new therapeutic approaches. SummaryThis review gives a detailed description of alterations in polyadenylation in endocrine disease, an overview of the current literature on polyadenylation and summarizes the clinical implications of the current state of research in this field.

Psychodrama Research-Therapy and Theory: A Critical Analysis of an Arrested Modality.

Science.gov (United States)

D'Amato, Rik Carl; Dean, Raymond S.

1988-01-01

Reviewed both theoretical foundation and therapeutic implications of psychodrama, therapy using theatrical principles as clients act out problems. Used social psychological and psychodramatic perspectives to evaluate psychodrama research in areas of therapeutic strategies, case illustration reports, and controlled research. Results suggest need…

Therapeutic action and the analyst's responsibility.

Science.gov (United States)

Greenberg, Jay

2015-02-01

Models of the psychoanalytic situation can usefully be thought of as fictions. Viewed this way, the models can be understood as narrative structures that shape what we are able to see and how we are able to think about what happens between us and our analysands. Theories of therapeutic action are elements of what can be called a "controlling fiction," mediating between these theories and our very real responsibilities, both to our preferred method and to a suffering patient. This venture into comparative psychoanalysis is illustrated by a discussion of published case material. © 2015 by the American Psychoanalytic Association.

Development of Potential Small Molecule Therapeutics for Treatment of Ebola Virus.

Science.gov (United States)

Schafer, Adam Michael; Cheng, Han; Lee, Charles; Du, Ruikun; Han, Julianna; Perez, Jasmine; Peet, Norton; Manicassamy, Balaji; Rong, Lijun

2017-10-10

Ebola virus has caused 26 outbreaks in 10 different countries since its identification in 1976, making it one of the deadliest emerging viral pathogens. The most recent outbreak in West Africa from 2014-16 was the deadliest yet and culminated in 11,310 deaths out of 28,616 confirmed cases. Currently there are no FDA-approved therapeutics or vaccines to treat Ebola virus infections. The slow development of effective vaccines combined with the severity of past outbreaks emphasizes the need to accelerate research into understanding the virus lifecycle and the development of therapeutics for post exposure treatment. Here we present a summary of the major findings on the Ebola virus replication cycle and the therapeutic approaches explored to treat this devastating disease. The major focus of this review is on small molecule inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

New and exploratory therapeutic agents for asthma

National Research Council Canada - National Science Library

Yeadon, Michael; Diamant, Zuzana

2000-01-01

... been accomplished. It is well recognized that new drugs are essentially the result of basic and applied research. Early in this century, the advent of a chemical approach to medicine led to many extraordinary developments. The past few decades have been characterized by a search to understand the mechanisms of disease- a quest spurred by the recognition that if pathogenic processes were known, new therapeutic opportunities would ensue. The validity of this concept is beautifully illustrated in the case of asthma. Here is a d...

The practice and clinical implications of tablet splitting in international health

Science.gov (United States)

Elliott, Ivo; Mayxay, Mayfong; Yeuichaixong, Sengchanh; Lee, Sue J; Newton, Paul N

2014-01-01

Objective Tablet splitting is frequently performed to facilitate correct dosing, but the practice and implications in low-income settings have rarely been discussed. Methods We selected eight drugs, with narrow therapeutic indices or critical dosages, frequently divided in the Lao PDR (Laos). These were split, by common techniques used in Laos, by four nurses and four laypersons. The mean percentage deviation from the theoretical expected weight and weight loss of divided tablets/capsules were recorded. Results Five of eight study drugs failed, on splitting, to meet European Pharmacopoeia recommendations for tablet weight deviation from the expected weight of tablet/capsule halves with 10% deviating by more than 25%. There was a significant difference in splitting accuracy between nurses and laypersons (P = 0.027). Coated and unscored tablets were less accurately split than uncoated (P = 0.03 and 0.0019 for each half) and scored (0.0001 for both halves) tablets. Conclusion These findings have potential clinical implications on treatment outcome and the development of antimicrobial resistance. Investment by drug companies in a wider range of dosage units, particularly for narrow therapeutic index and critical dosage medicines, is strongly recommended. PMID:24702766

[Therapeutic education didactic techniques].

Science.gov (United States)

Valverde, Maite; Vidal, Mercè; Jansa, Margarida

2012-10-01

This article includes an introduction to the role of Therapeutic Education for Diabetes treatment according to the recommendations of the American Diabetes Association (ADA), the Diabetes Education Study Group (DESG) of the "European Association for Study of Diabetes (EASD) and the clinical Practice Guidelines (CPG) of the Spanish Ministry of Health. We analyze theoretical models and the differences between teaching vs. learning as well as current trends (including Internet), that can facilitate meaningful learning of people with diabetes and their families and relatives. We analyze the differences, similarities, advantages and disadvantages of individual and group education. Finally, we describe different educational techniques (metaplan, case method, brainstorming, role playing, games, seminars, autobiography, forums, chats,..) applicable to individual, group or virtual education and its application depending on the learning objective.

Oxidative stress drivers and modulators in obesity and cardiovascular disease: from biomarkers to therapeutic approach.

Science.gov (United States)

Santilli, F; Guagnano, M T; Vazzana, N; La Barba, S; Davi, G

2015-01-01

This review article is intended to describe how oxidative stress regulates cardiovascular disease development and progression. Epigenetic mechanisms related to oxidative stress, as well as more reliable biomarkers of oxidative stress, are emerging over the last years as potentially useful tools to design therapeutic approaches aimed at modulating enhanced oxidative stress "in vivo", thereby mitigating the consequent atherosclerotic burden. As a paradigm, we describe the case of obesity, in which the intertwining among oxidative stress, due to caloric overload, chronic low-grade inflammation induced by adipose tissue dysfunction, and platelet activation represents a vicious cycle favoring the progression of atherothrombosis. Oxidative stress is a major player in the pathobiology of cardiovascular disease (CVD). Reactive oxygen species (ROS)- dependent signaling pathways prompt transcriptional and epigenetic dysregulation, inducing chronic low-grade inflammation, platelet activation and endothelial dysfunction. In addition, several oxidative biomarkers have been proposed with the potential to improve current understanding of the mechanisms underlying CVD. These include ROS-generating and/or quenching molecules, and ROS-modified compounds, such as F2-isoprostanes. There is also increasing evidence that noncoding micro- RNA (mi-RNA) are critically involved in post- transcriptional regulation of cell functions, including ROS generation, inflammation, regulation of cell proliferation, adipocyte differentiation, angiogenesis and apoptosis. These molecules have promising translational potential as both markers of disease and site of targeted interventions. Finally, oxidative stress is a critical target of several cardioprotective drugs and nutraceuticals, including antidiabetic agents, statins, renin-angiotensin system blockers, polyphenols and other antioxidants. Further understanding of ROS-generating mechanisms, their biological role as well as potential therapeutic

The Prognostic, Diagnostic, and Therapeutic Potential of Tumor Antigens

DEFF Research Database (Denmark)

Olsen, Lars Rønn

or abundance in cancer cells is often unique and their roles and functions in tumorigenesis are, in many cases, studied extensively. They, therefore, have the potential to be highly specific biomarkers as well as therapeutic targets, but complex analysis combining basic science, high-throughput methods...... of genomics and proteomics, and clinical studies need to be combined. These analyses produce large amounts of data that require advanced bioinformatics methods for collection, management, integration and interpretation. In this thesis, I have explored the potential of tumor antigens as biomarkers...... and therapeutic agents, by developing and implementing several computational tools and databases for immunotherapy target discovery, and have analyzed the potential of tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas. In this analysis I have shown that the combination of proteomics...

Determining the status of non-transferred embryos in Ireland: a conspectus of case law and implications for clinical IVF practice.

LENUS (Irish Health Repository)

Sills, Eric Scott

2009-01-01

The development of in vitro fertilisation (IVF) as a treatment for human infertilty was among the most controversial medical achievements of the modern era. In Ireland, the fate and status of supranumary (non-transferred) embryos derived from IVF brings challenges both for clinical practice and public health policy because there is no judicial or legislative framework in place to address the medical, scientific, or ethical uncertainties. Complex legal issues exist regarding informed consent and ownership of embryos, particularly the use of non-transferred embryos if a couple separates or divorces. But since case law is only beginning to emerge from outside Ireland and because legislation on IVF and human embryo status is entirely absent here, this matter is poised to raise contractual, constitutional and property law issues at the highest level. Our analysis examines this medico-legal challenge in an Irish context, and summarises key decisions on this issue rendered from other jurisdictions. The contractual issues raised by the Roche case regarding informed consent and the implications the initial judgment may have for future disputes over embryos are also discussed. Our research also considers a putative Constitutional \\'right to procreate\\' and the implications EU law may have for an Irish case concerning the fate of frozen embryos. Since current Medical Council guidelines are insufficient to ensure appropriate regulation of the advanced reproductive technologies in Ireland, the report of the Commission on Assisted Human Reproduction is most likely to influence embryo custody disputes. Public policy requires the establishment and implementation of a more comprehensive legislative framework within which assisted reproductive medical services are offered.

Determining the status of non-transferred embryos in Ireland: a conspectus of case law and implications for clinical IVF practice.

Science.gov (United States)

Sills, Eric Scott; Murphy, Sarah Ellen

2009-07-09

The development of in vitro fertilisation (IVF) as a treatment for human infertilty was among the most controversial medical achievements of the modern era. In Ireland, the fate and status of supranumary (non-transferred) embryos derived from IVF brings challenges both for clinical practice and public health policy because there is no judicial or legislative framework in place to address the medical, scientific, or ethical uncertainties. Complex legal issues exist regarding informed consent and ownership of embryos, particularly the use of non-transferred embryos if a couple separates or divorces. But since case law is only beginning to emerge from outside Ireland and because legislation on IVF and human embryo status is entirely absent here, this matter is poised to raise contractual, constitutional and property law issues at the highest level. Our analysis examines this medico-legal challenge in an Irish context, and summarises key decisions on this issue rendered from other jurisdictions. The contractual issues raised by the Roche case regarding informed consent and the implications the initial judgment may have for future disputes over embryos are also discussed. Our research also considers a putative Constitutional 'right to procreate' and the implications EU law may have for an Irish case concerning the fate of frozen embryos. Since current Medical Council guidelines are insufficient to ensure appropriate regulation of the advanced reproductive technologies in Ireland, the report of the Commission on Assisted Human Reproduction is most likely to influence embryo custody disputes. Public policy requires the establishment and implementation of a more comprehensive legislative framework within which assisted reproductive medical services are offered.

Implications of Biodiesel-Induced Land-Use Changes for CO2 Emissions: Case Studies in Tropical America, Africa, and Southeast Asia

Directory of Open Access Journals (Sweden)

Wouter M. J. Achten

2011-12-01

Full Text Available Biofuels are receiving growing negative attention. Direct and/or indirect land-use changes that result from their cultivation can cause emissions due to carbon losses in soils and biomass and could negate any eventual greenhouse gas (GHG reduction benefit. This paper evaluates the implications of land-use change emission on the climate-change mitigation potential of different biofuel production systems in 12 case studies in six countries. We calculated carbon debts created by conversion of different land-use types, ranging from annual cropland to primary forest. We evaluated case studies using three different biofuel crops: oil palm, Jatropha, and soybean. The time needed for each biofuel production system to pay back its carbon debt was calculated based on a life-cycle assessment of the GHG reduction potentials of the system. Carbon debts range from 39 to 1743.7 Mg C02 ha-1. The oil palm case studies created the largest carbon debts (472.8-1743.7 t C02 ha-1 because most of the area expansion came at the expense of dense tropical forest. The highest debt was associated with plantation on peatland. For all cases evaluated, only soybean in Guarantã do Norte and Alta Floresta, Brazil needed less than one human generation (30 years to repay the initial carbon debt. Highest repayment times were found for Jatropha (76-310 years and oil palm (59-220 years case studies. Oil palm established in peatlands had the greatest repayment times (206-220 years. High repayment times for Jatropha resulted from the combined effects of land-cover change and low CO2 emission reduction rate. These outcomes raise serious questions about the sustainability of biofuel production. The carbon implications of conversion of (semi-natural systems with medium to high biomass indicate that, in order to generate climate benefits, cultivation of biofuel feedstocks should be restricted to areas that already have low carbon content.

The Life Course Implications of Ready to Use Therapeutic Food for Children in Low-Income Countries.

Science.gov (United States)

Bazzano, Alessandra N; Potts, Kaitlin S; Bazzano, Lydia A; Mason, John B

2017-04-11

The development of ready-to-use therapeutic food (RUTF) for the treatment of uncomplicated cases of severe acute malnutrition in young children from 6 months to 5 years old has greatly improved survival through the ability to treat large numbers of malnourished children in the community setting rather than at health facilities during emergencies. This success has led to a surge in demand for RUTF in low income countries that are frequently food insecure due to environmental factors such as cyclical drought. Worldwide production capacity for the supply of RUTF has increased dramatically through the expansion and development of new manufacturing facilities in both low and high income countries, and new business ventures dedicated to ready-to-use foods have emerged not only for emergencies, but increasingly, for supplementing caloric intake of pregnant women and young children not experiencing acute undernutrition. Due to the lack of evidence on the long term health impact these products may have, in the midst of global nutrition transitions toward obesity and metabolic dysfunction, the increased use of manufactured, commercial products for treatment and prevention of undernutrition is of great concern. Using a framework built on the life course health development perspective, the current research presents several drawbacks and limitations of RUTF for nutrition of mothers and young children, especially in non-emergency situations. Recommendations follow for potential strategies to limit the use of these products to the treatment of acute undernutrition only, study the longer term health impacts of RUTF, prevent conflict of interests arising for social enterprises, and where possible, ensure that whole foods are supported for life-long health and nutrition, as well as environmental sustainability.

Therapeutic values, chemical constituents and toxicity of Taiwanese Dysosma pleiantha--a review.

Science.gov (United States)

Karuppaiya, Palaniyandi; Tsay, Hsin Sheng

2015-07-16

Dysosma pleiantha (Hance) Woodson also called as Bajiaolian belongs to the family Berberidaceae, is widely used in Taiwan as traditional Chinese herbal medicine for more than thousands of years. It is usually recommended by various traditional Chinese medical doctors and herbal pharmacies for general remedies including postpartum recovery, treatment of weakness, neck mass, acne, hepatoma, lumbago, snakebite, tumor growth and dysmenorrhea. In the textbooks of traditional Chinese medicine, there is limited information about the toxicity of Bajiaolian. Podophyllotoxin, a lignan is the main toxic ingredient of Bajiaolian rhizome. Therefore, Bajiaolian is documented as the fifth highest cause of poisoning among the herbal medicine in Taiwan. Since the therapeutic and toxic doses are very close, Bajiaolian poisoning cases are frequently reported in Taiwan. Moreover, Dysosma poisoning cases are difficult to diagnosis because physicians are unfamiliar with this medicine's multiple clinical presentations in different stages of intoxication. Therefore, the objective of this review is to represent the collective information available in literatures regarding D. pleiantha, a cytotoxic lignan containing medicinal plant. Specifically, the literatures have been reviewed for articles pertaining to chemical constituents, properties, therapeutical benefits, toxicity, poisoning symptoms, toxic as well as therapeutic dose and medical management. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dendritic cell-based vaccination in cancer: therapeutic implications emerging from murine models

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Soledad eMac Keon

2015-05-01

Full Text Available Dendritic cells (DCs play a pivotal role in the orchestration of immune responses, and are thus key targets in cancer vaccine design. Since the 2010 FDA approval of the first cancer DC-based vaccine (Sipuleucel T there has been a surge of interest in exploiting these cells as a therapeutic option for the treatment of tumors of diverse origin. In spite of the encouraging results obtained in the clinic, many elements of DC-based vaccination strategies need to be optimized. In this context, the use of experimental cancer models can help direct efforts towards an effective vaccine design. This paper reviews recent findings in murine models regarding the antitumoral mechanisms of DC-based vaccination, covering issues related to antigen sources, the use of adjuvants and maturing agents, and the role of DC subsets and their interaction in the initiation of antitumoral immune responses. The summary of such diverse aspects will highlight advantages and drawbacks in the use of murine models, and contribute to the design of successful DC-based translational approaches for cancer treatment.

Colorectal cancer: diagnostic and therapeutic strategies

International Nuclear Information System (INIS)

Vaillant, J.C.

1996-01-01

Technical advances that has been achieved during the past two decades have not dramatically improved the 35 % five-year rate observed in patients with colorectal cancer. These tumours remain one of the most challenging problems in public health policies in western countries. Screening applies to some subgroups of high-risk individuals and the general population aged over 50. In order to improve their efficacy, such screening programs imply large-scale information campaigns and a strong cooperation with the general physicians. The diagnosis is strongly suggested by any recent modification of bowel habits ad by rectal bleeding. It has to be confirmed by rectal examination and by colonoscopy which allows sampling to the tumour. Loco-regional and distant metastatic tumour spread must be assessed precisely before any therapeutic strategy is decided. Surgery, which resects the tumour en bloc with the corresponding lymphatic territories, is the only treatment that can achieve long term cure. In localized tumours, surgery alone can provide patients with 5-years survival rates close to 95 %. On the other hand, surgery alone is not sufficient to cure patients with advances cancers. In recent years, several adjuvant therapeutic modalities have been shown to improve the results of surgery in these cases (rectal cancer: pre-operative radiotherapy or post-operative radio-chemotherapy, colon cancer with nodal metastases: post-operative chemotherapy). There is a hope that a better use of our diagnostic and therapeutic armementarium would be able to avoid or to cure up to 75 % of the colorectal cancers we are dealing with. (author)

The necessary conditions of engagement for the therapeutic relationship in physiotherapy: an interpretive description study.

Science.gov (United States)

Miciak, Maxi; Mayan, Maria; Brown, Cary; Joyce, Anthony S; Gross, Douglas P

2018-01-01

The therapeutic relationship between patient and physiotherapist is a central component of patient-centred care and has been positively associated with better physiotherapy clinical outcomes. Despite its influence, we do not know what conditions enable a physiotherapist and patient to establish and maintain a therapeutic relationship. This knowledge has implications for how clinicians approach their interactions with patients and for the development of an assessment tool that accurately reflects the nature of the therapeutic relationship. Therefore, this study's aim was to identify and provide in-depth descriptions of the necessary conditions of engagement of the therapeutic relationship between physiotherapists and patients. Interpretive description was the qualitative methodological orientation used to identify and describe the conditions that reflect and are practically relevant to clinical practice. Eleven physiotherapists with a minimum 5 years of clinical experience and seven adult patients with musculoskeletal disorders were purposively sampled from private practice clinics in Edmonton, Canada. The in-person, semi-structured interviews were completed in a location of the participant's choice and were audio recorded and transcribed. Qualitative content analysis was used to analyze the textual data and constant comparison techniques were integrated to refine the categories and sub-categories. Rigour strategies used throughout the study were peer debrief, interview notes, reflexive journaling, memoing, member reflections, audit trail, and external audit. Four conditions were identified as necessary for establishing a therapeutic relationship: present , receptive , genuine , and committed . These conditions represent the intentions and attitudes of physiotherapists and patients engaging in the clinical interaction. Although distinct, the conditions appear related as being present and receptive create a foundation for being genuine and committed. These

Activation of sigma-1 receptor chaperone in the treatment of neuropsychiatric diseases and its clinical implication

Directory of Open Access Journals (Sweden)

Kenji Hashimoto

2015-01-01

Full Text Available Endoplasmic reticulum (ER protein sigma-1 receptor represents unique chaperone activity in the central nervous system, and it exerts a potent influence on a number of neurotransmitter systems. Several lines of evidence suggest that activation of sigma-1 receptor plays a role in the pathophysiology of neuropsychiatric diseases, as well as in the mechanisms of some therapeutic drugs and neurosteroids. Preclinical studies showed that some selective serotonin reuptake inhibitors (SSRIs; fluvoxamine, fluoxetine, excitalopram, donepezil, and ifenprodil act as sigma-1 receptor agonists. Furthermore, sigma-1 receptor agonists could improve the N-methyl-D-aspartate (NMDA antagonist phencyclidine (PCP-induced cognitive deficits in mice. A study using positron emission tomography have demonstrated that an oral administration of fluvoxamine or donepezil could bind to sigma-1 receptor in the healthy human brain, suggesting that sigma-1 receptor might be involved in the therapeutic mechanisms of these drugs. Moreover, case reports suggest that sigma-1 receptor agonists, including fluvoxamine, and ifenprodil, may be effective in the treatment of cognitive impairment in schizophrenia, delirium in elderly people, and flashbacks in post-traumatic stress disorder. In this review article, the author would like to discuss the clinical implication of sigma-1 receptor agonists, including endogenous neurosteroids, in the neuropsychiatric diseases.

Therapeutic Riding for a Student with Multiple Disabilities and Visual Impairment: A Case Study.

Science.gov (United States)

Lehrman, Jennifer; Ross, David B.

2001-01-01

A 9-year-old with multiple disabilities and visual impairments was the focus of a 10-week developmental therapeutic riding program incorporating hippotherapy. The program has led to increased mobility, an increase in visual attention span and fixation time, signs of greater verbal communication, and the acquisition of new functional signs.…

Therapeutic embolization in pulmonary hemorrhage

International Nuclear Information System (INIS)

Gasparini, D.

1989-01-01

The author's purpose was to evaluate the efficacy of therapeutic embolization in pulmonary hemorrage performed with fibrin foam (Spongostan) suspended in sclerosing agents (hidroxy-poliethoxy-dodecano 3%, or natrium morruate 5%), and electrocoagulation (Bitrol, spa) as an alternative to surgery. Twenty patients were embolized: 17 with fibrin foam and sclerosing agents only, 2 with the addition of electrocoagulation and a Gianturco coil respectively, and 1 with electrocoagulation alone. The follow-up ranges from 3 to 42 months (average 22). A patient affected by aspergilloma died a few days after hemoptysis. The patient treated by electrocoagulation alone suffers from periodical hematic expectoration (spitting). The remaining 18 patients have not shown any pathological findings. In 2 cases the arterial occlusion was confirmed by angiography, while in 1 case partial arterial recanalization was observed. Such a finding was due to the vessel dimensions and to hyperflux values. In similar cases, obstruction must be completed different techniques (e.g. Gianturco coils, electrocoagulation, detachable balloons, etc.). The absence of flux resulting from embolization improves electrocoagulation efficiency, which should be considered as the technique of choice. Even though additional trials are needed, the techniques have proven quite reliable and suitable to replace surgery in low-aggression lesions

Intrathecal delivery of protein therapeutics to the brain: a critical reassessment.

Science.gov (United States)

Calias, Pericles; Banks, William A; Begley, David; Scarpa, Maurizio; Dickson, Patricia

2014-11-01

Disorders of the central nervous system (CNS), including stroke, neurodegenerative diseases, and brain tumors, are the world's leading causes of disability. Delivery of drugs to the CNS is complicated by the blood-brain barriers that protect the brain from the unregulated leakage and entry of substances, including proteins, from the blood. Yet proteins represent one of the most promising classes of therapeutics for the treatment of CNS diseases. Many strategies for overcoming these obstacles are in development, but the relatively straightforward approach of bypassing these barriers through direct intrathecal administration has been largely overlooked. Originally discounted because of its lack of usefulness for delivering small, lipid-soluble drugs to the brain, the intrathecal route has emerged as a useful, in some cases perhaps the ideal, route of administration for certain therapeutic protein and targeted disease combinations. Here, we review blood-brain barrier functions and cerebrospinal fluid dynamics and their relevance to drug delivery via the intrathecal route, discuss animal and human studies that have investigated intrathecal delivery of protein therapeutics, and outline several characteristics of protein therapeutics that can allow them to be successfully delivered intrathecally. Copyright © 2014 Elsevier Inc. All rights reserved.

Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy.

Directory of Open Access Journals (Sweden)

Julia Pollak

Full Text Available Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer, suggesting that ion channel expression may be perturbed in this population. However, little is known about the expression and functional relevance of ion channels that may contribute to GSC malignancy. Using RNA sequencing, we assessed the enrichment of ion channels in GSC isolates and non-tumor neural cell types. We identified a unique set of GSC-enriched ion channels using differential expression analysis that is also associated with distinct gene mutation signatures. In support of potential clinical relevance, expression of selected GSC-enriched ion channels evaluated in human glioblastoma databases of The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project correlated with patient survival times. Finally, genetic knockdown as well as pharmacological inhibition of individual or classes of GSC-enriched ion channels constrained growth of GSCs compared to normal neural stem cells. This first-in-kind global examination characterizes ion channels enriched in GSCs and explores their potential clinical relevance to glioblastoma molecular subtypes, gene mutations, survival outcomes, regional tumor expression, and experimental responses to loss-of-function. Together, the data support the potential biological and therapeutic impact of ion channels on GSC malignancy and provide strong rationale for further examination of their mechanistic and therapeutic importance.

Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy.

Science.gov (United States)

Pollak, Julia; Rai, Karan G; Funk, Cory C; Arora, Sonali; Lee, Eunjee; Zhu, Jun; Price, Nathan D; Paddison, Patrick J; Ramirez, Jan-Marino; Rostomily, Robert C

2017-01-01

Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs) are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer, suggesting that ion channel expression may be perturbed in this population. However, little is known about the expression and functional relevance of ion channels that may contribute to GSC malignancy. Using RNA sequencing, we assessed the enrichment of ion channels in GSC isolates and non-tumor neural cell types. We identified a unique set of GSC-enriched ion channels using differential expression analysis that is also associated with distinct gene mutation signatures. In support of potential clinical relevance, expression of selected GSC-enriched ion channels evaluated in human glioblastoma databases of The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project correlated with patient survival times. Finally, genetic knockdown as well as pharmacological inhibition of individual or classes of GSC-enriched ion channels constrained growth of GSCs compared to normal neural stem cells. This first-in-kind global examination characterizes ion channels enriched in GSCs and explores their potential clinical relevance to glioblastoma molecular subtypes, gene mutations, survival outcomes, regional tumor expression, and experimental responses to loss-of-function. Together, the data support the potential biological and therapeutic impact of ion channels on GSC malignancy and provide strong rationale for further examination of their mechanistic and therapeutic importance.

Autophagy and Alzheimer’s Disease: From Molecular Mechanisms to Therapeutic Implications

Directory of Open Access Journals (Sweden)

Md. Sahab Uddin

2018-01-01

Full Text Available Alzheimer’s disease (AD is the most common cause of progressive dementia in the elderly. It is characterized by a progressive and irreversible loss of cognitive abilities and formation of senile plaques, composed mainly of amyloid β (Aβ, and neurofibrillary tangles (NFTs, composed of tau protein, in the hippocampus and cortex of afflicted humans. In brains of AD patients the metabolism of Aβ is dysregulated, which leads to the accumulation and aggregation of Aβ. Metabolism of Aβ and tau proteins is crucially influenced by autophagy. Autophagy is a lysosome-dependent, homeostatic process, in which organelles and proteins are degraded and recycled into energy. Thus, dysfunction of autophagy is suggested to lead to the accretion of noxious proteins in the AD brain. In the present review, we describe the process of autophagy and its importance in AD. Additionally, we discuss mechanisms and genes linking autophagy and AD, i.e., the mTOR pathway, neuroinflammation, endocannabinoid system, ATG7, BCL2, BECN1, CDK5, CLU, CTSD, FOXO1, GFAP, ITPR1, MAPT, PSEN1, SNCA, UBQLN1, and UCHL1. We also present pharmacological agents acting via modulation of autophagy that may show promise in AD therapy. This review updates our knowledge on autophagy mechanisms proposing novel therapeutic targets for the treatment of AD.

Clinical, Epidemiological and Therapeutic Evaluation in 14 Cases of Inflammatory Breast Cancer in Canines

Directory of Open Access Journals (Sweden)

Celina Gomes da Silva

2014-06-01

Full Text Available With the aim of evaluating clinical aspects, age, breed, presence of metastasis, chemotherapeutical protocol, use of COX-2 inhibitors and survival rate in female dogs diagnosed with inflammatory carcinoma at the Hospital Veterinario de Uberaba (HVU, a retrospective analysis was performed on the medical records of 14 female dogs seen at HVU between July, 2011 and July, 2012 and diagnosed with inflammatory breast cancer. The breeds included were crossbred, poodle, Brazilian terrier, teckel and Belgian shepherd. Average age: 11.1 years. Outbreaks of distant metastasis were detected in 7 animals, out of which 5 patients received COX-2 inhibitors as sole treatment and only 4 received chemotherapeutical treatment. The protocol, constituted by piroxicam, cyclophosphamide, carboplatin and doxorubicin showed the highest survival time (210 days. In conclusion, inflammatory carcinoma is a disease of bad prognosis, short survival time and produces systemic alterations that reduce therapeutic response. Apparently, the most accurate therapeutic form is the association of COX-2 inhibitors and chemotherapeutics; however, controlled clinical studies are needed in order to evaluate these suggestions.

Evaluation of therapeutic response with 18-FDG PET-CT for non-small cell lung cancer: case report and literature review

International Nuclear Information System (INIS)

Bitencourt, Almir G.V.; Lima, Eduardo N.P.; Chojniak, Rubens; Haddad, Fabio J.; Dettino, Aldo L.A.; Cavicchioli, Marcelo; Torres, Ivone C.G.

2010-01-01

Positron Emission Tomography / Computed Tomography (PET-CT) is increasingly being used as to complement conventional imaging methods and improve the management of patients with non-small cells lung cancer (NSCLC). The objective of this work is to report on a case in which PET-CT was used as a complementary method to evaluate the therapeutic response in a patient with NSCLC, and to carry out a literature review of the theme. Female patient, 65 years-old, with NSCLC, stage IIIA (T2N2M0), was submitted to exclusive neoadjuvant chemotherapy and presented good response to the treatment, classified by the morphological criteria of the RECIST (Response Evaluation Criteria in Solid Tumors) as a partial response (reduction equal to or greater than 30% in the sum of the widest diameter of all the target lesions in the computed tomography). The metabolic evaluation by PET-CT showed a complete response (reduction equal to or higher than 80% at maximum SUV of the lesions), which was confirmed in the histopathological analysis of the surgical samples. In the case presented, and through the literature review, we show that the evaluation of response with metabolic criteria, associated with morphological criteria, may be more accurate than the use of morphological criteria alone. (author)

The effect of a therapeutic lithium level on a stroke-related cerebellar tremor.

Science.gov (United States)

Orleans, Rachel A; Dubin, Marc J; Kast, Kristopher A

2018-01-24

Lithium is a mood stabiliser used in the treatment of acute mania, bipolar disorder and as augmentation for unipolar major depression. Tremor is a common adverse effect associated with lithium at both therapeutic and toxic serum levels. We present a case of dose-dependent changes in the quality and intensity of a stroke-related, chronic cerebellar tremor with lithium treatment at serum levels within the therapeutic range. On admission, the patient in this case had a baseline fine, postural tremor, which increased in frequency and evolved to include myoclonic jerks once lithium therapy was initiated. Although the patient's serum lithium level was never in the toxic range, his tremor returned to baseline on reduction of his serum lithium level. This case highlights that a pre-existing, baseline tremor may lower the threshold for developing myoclonus. It also suggests that caution may be warranted with lithium therapy in the setting of known cerebellar disease. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Severe Hyperthyroidism Complicated by Agranulocytosis Treated with Therapeutic Plasma Exchange: Case Report and Review of the Literature.

Science.gov (United States)

Garla, Vishnu; Kovvuru, Karthik; Ahuja, Shradha; Palabindala, Venkatataman; Malhotra, Bharat; Abdul Salim, Sohail

2018-01-01

To present a case of Graves' disease complicated by methimazole induced agranulocytosis treated with therapeutic plasma exchange (TPE) and review of the literature. A 21-year-old patient with a history of Graves' disease presented to the endocrine clinic. His history was significant for heat intolerance, weight loss, and tremors. Upon examination he had tachycardia, smooth goiter, thyroid bruit, and hyperactive reflexes. He was started on methimazole and metoprolol and thyroidectomy was to be done once his thyroid function tests normalized. On follow-up, the patient symptoms persisted. Complete blood count done showed a white blood cell count of 2100 (4000-11,000 cells/cu mm) with a neutrophil count of 400 cells/cu mm, consistent with neutropenia. He was admitted to the hospital and underwent 3 cycles of TPE and was also given filgrastim. He improved clinically and his thyroxine (T4) levels also came down. Thyroidectomy was done. He was discharged on levothyroxine for postsurgical hypothyroidism. Plasmapheresis may be useful in the treatment of hyperthyroidism. It works by removing protein bound hormones and also possibly inflammatory cytokines. Further studies are needed to clarify the role of various modalities of TPE in the treatment of hyperthyroidism.

Therapeutic Nanodevices

Science.gov (United States)

Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

Protein Changes in Sulfur Mustard Exposure: Diagnostic and Therapeutic Implications

International Nuclear Information System (INIS)

Ray, P.; Jin, X.; Ray, R.

2007-01-01

Laminin-5, a heterotrimer of laminin α3, β3, and γ2 subunits, is a component of the skin basal epithelium. Laminin-5 functions as a ligand of the α3β1 and α6β4 integrins in epidermal keratinocytes to regulate cell adhesion, migration, morphogenesis, and assembly of basement membranes; thus it is essential for a stable attachment of the epidermis to the dermis and recovery of damaged skin. Sulfur mustard (SM), also known as mustard gas, is a vesicant chemical warfare and terrorism agent. Skin exposure to SM results in fluid-filled blisters; proposed mechanisms are inflammation, protease stimulation, basal cell death, and separation of the epidermis from the dermis apparently due to the degradation of attachment proteins like laminin-5. Therefore, we investigated the effects of SM exposure on the degradation of laminin-5 by exposing normal human epidermal keratinocytes (NHEK) to SM (0-300 μM, 1-24 hours). We found that SM degraded laminin-5 and its two subunits β3 and γ2, but not α3. Preincubation of cells with a serine protease inhibitor (PMSF), or a metalloprotease inhibitor (1, 10-phenanthroline) prior to SM exposure partially prevented SM-induced degradation of laminin-5 subunits, β3 and γ2. Regarding specificity, laminin-5 γ2 was degraded due to a bifunctional mustard compound like SM, but not due to the other alkylating agents tested. Our results support that laminin-5 degradation is an important mechanism of SM injury as well as a useful biomarker of SM exposure. This knowledge of the mechanism of laminin-5 degradation due to SM has potential application in developing cutaneous therapeutics against SM.(author)

Macromolecular therapeutics.

Science.gov (United States)

Yang, Jiyuan; Kopeček, Jindřich

2014-09-28

This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines - (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. Copyright © 2014 Elsevier B.V. All rights reserved.

Therapeutic effectiveness of pediatric renal transplantation in 63 cases

Institute of Scientific and Technical Information of China (English)

Han Shu; Wang Mu; Zhu Youhua; Zeng Li; Zhou Meisheng; Zhang Lei; Fu Shangxi; Wang Liming

2008-01-01

Objective: To explore the characteristic of operation, intra-operation treatment and the application of immunosuppressant in pediatric renal transplantation in order to improve therapeutic effectiveness. Methods: From March 1986 to October 2006, the clinical data of 63 children who underwent renal transplantation in our hospital were retrospectively analyzed. Results: The 1-, 3-, 5-, 10-year graft survival rates were 98.4%, 90.5%, 88.9% and 68.3%,respectively. And the corresponding patient survival rates were 100%, 95.2%, 92.1%, 71.4%. The body weight increased 4 to 12 kg and the body height grew up 2 to 6 cm during the first year post-transplantation. The main complications in the first year post-transplantation were hypertension (26/63, 41.3%), crinosity (14/63, 22.2%),drug-induced hepatic injury(11/63, 17.5%), gingival hyperplasia (10/63, 15.8%), pulmonary infection(9/63, 14.3%),bone marrow suppression(5/63, 7.9%), herpes (4/63, 6.3%) and diabetes (3/63, 4.8%). Conclusion: Renal transplantation is a preferred method for the treatment of children in end-stage renal disease (ESRD). Good tissue matching, proper operative time and pattern, peri-operactive care were essential to success, as well as appropriate immuno-suppressant strategy and good compliance.

Evaluation of 201Tl stress-redistribution imaging for the detection of myocardial ischemia and assessment of its therapeutic effect (40 cases attached)

International Nuclear Information System (INIS)

Lin Jinghui

1989-01-01

The characteristics of 201 Tl stress-redistribution imagings of 21 normal controls and 19 myocardial ischemia were reported. Normal variability of myocardial images and its influencing factors were discussed as well. All of 40 cases were also undergoing coronary arteriography (CAG), and exercise ECG. Taken the stenosis of coronary artery > 50% by CAG as the criterion of diagnosis of CHD, the sensitivity and specificity of 201 Tl image were 94.7% and 100%, while as exercise ECG were 66.6% and 80.9% respectively. 2 patients with bypass surgery and 6 patients with PTCA were examined pre- and postoperatively by 201 Tl images. The results indicated that this technique was noninvasive and reliable also for the assessment of their therapeutic effect and follow up studies

Therapeutic approach to Gradenigo's syndrome: a case report

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Aspris Andreas

2010-05-01

Full Text Available Abstract Introduction Traditional management of Gradenigo's syndrome requires aggressive and radical surgery without any attempt to preserve hearing. Recent reports, however, describe a successful outcome after conservative surgical intervention without labyrinthectomy. A similar outcome has also been reported in patients who were only prescribed with antibiotics and did not undergo myringotomy. Case presentation We report the case of a 24-year-old Caucasian Greek woman with Gradenigo's syndrome who was treated by draining her petrous apex via an infralabyrithine approach between her posterior semicircular canal and the jugular bulb. Her inner ear was not sacrificed during the procedure. She presented pre-operatively with ipsilateral conductive hearing loss, which recovered completely four weeks after the surgery. Conclusions Patients with Gradenigo's syndrome may be successfully treated with a combination of long-term permanent drainage and ventilation of the apical cells with corresponding hearing preservation. This can be achieved via a combination of transmastoid, infralabyrinthine and suprajugular approaches, if such would be allowed by the anatomy of the region or if there is enough space between the posterior semicircular canal and the jugular bulb.

Combining Radiation Epidemiology With Molecular Biology-Changing From Health Risk Estimates to Therapeutic Intervention.

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Abend, Michael; Port, Matthias

2016-08-01

The authors herein summarize six presentations dedicated to the key session "molecular radiation epidemiology" of the ConRad meeting 2015. These presentations were chosen in order to highlight the promise when combining conventional radiation epidemiology with molecular biology. Conventional radiation epidemiology uses dose estimates for risk predictions on health. However, combined with molecular biology, dose-dependent bioindicators of effect hold the promise to improve clinical diagnostics and to provide target molecules for potential therapeutic intervention. One out of the six presentations exemplified the use of radiation-induced molecular changes as biomarkers of exposure by measuring stabile chromosomal translocations. The remaining five presentations focused on molecular changes used as bioindicators of the effect. These bioindicators of the effect could be used for diagnostic purposes on colon cancers (genomic instability), thyroid cancer (CLIP2), or head and neck squamous cell cancers. Therapeutic implications of gene expression changes were examined in Chernobyl thyroid cancer victims and Mayak workers.

Bee venom therapy: Potential mechanisms and therapeutic applications.

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Zhang, Shuai; Liu, Yi; Ye, Yang; Wang, Xue-Rui; Lin, Li-Ting; Xiao, Ling-Yong; Zhou, Ping; Shi, Guang-Xia; Liu, Cun-Zhi

2018-04-11

Bee venom is a very complex mixture of natural products extracted from honey bee which contains various pharmaceutical properties such as peptides, enzymes, biologically active amines and nonpeptide components. The use of bee venom into the specific points is so called bee venom therapy, which is widely used as a complementary and alternative therapy for 3000 years. A growing number of evidence has demonstrated the anti-inflammation, the anti-apoptosis, the anti-fibrosis and the anti-arthrosclerosis effects of bee venom therapy. With these pharmaceutical characteristics, bee venom therapy has also been used as the therapeutic method in treating rheumatoid arthritis, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, liver fibrosis, atherosclerosis, pain and others. Although widely used, several cases still reported that bee venom therapy might cause some adverse effects, such as local itching or swelling. In this review, we summarize its potential mechanisms, therapeutic applications, and discuss its existing problems. Copyright © 2018 Elsevier Ltd. All rights reserved.

Induced-Decay of Glycine Decarboxylase Transcripts as an Anticancer Therapeutic Strategy for Non-Small-Cell Lung Carcinoma

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Jing Lin

2017-12-01

Full Text Available Self-renewing tumor-initiating cells (TICs are thought to be responsible for tumor recurrence and chemo-resistance. Glycine decarboxylase, encoded by the GLDC gene, is reported to be overexpressed in TIC-enriched primary non-small-cell lung carcinoma (NSCLC. GLDC is a component of the mitochondrial glycine cleavage system, and its high expression is required for growth and tumorigenic capacity. Currently, there are no therapeutic agents against GLDC. As a therapeutic strategy, we have designed and tested splicing-modulating steric hindrance antisense oligonucleotides (shAONs that efficiently induce exon skipping (half maximal inhibitory concentration [IC50] at 3.5–7 nM, disrupt the open reading frame (ORF of GLDC transcript (predisposing it for nonsense-mediated decay, halt cell proliferation, and prevent colony formation in both A549 cells and TIC-enriched NSCLC tumor sphere cells (TS32. One candidate shAON causes 60% inhibition of tumor growth in mice transplanted with TS32. Thus, our shAONs candidates can effectively inhibit the expression of NSCLC-associated metabolic enzyme GLDC and may have promising therapeutic implications.

Therapeutic hypothermia brings favorable neurologic outcomes in children with near drowning.

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Chen, Ming-Chun; Chu, Chia-Hsiang; Cheng, Ching-Feng; Lin, Jun-Song; Chen, Jui-Hsia; Chang, Yu-Hsun

2016-01-01

A 1-year-10-month-old boy was admitted to our pediatric intensive care unit due to near drowning with pulmonary edema. A conventional ventilator with 100% oxygen supplementation was used initially, but was shifted to high frequency oscillatory ventilation as his oxygen saturation was around 84-88%. Therapeutic hypothermia was applied due to hypoxic ischemic encephalopathy with severe acidosis. His respiratory condition improved and he was extubated successfully on the 6 th hospital day. The patient had no obvious neurological defects and he was discharged in a stable condition after 17 days of hospitalization. Our case report demonstrates the advantages of therapeutic hypothermia on survival and neurological outcomes in treating pediatric near drowning patients.

Oxidative stress in cancer and fibrosis: Opportunity for therapeutic intervention with antioxidant compounds, enzymes, and nanoparticles

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Jingga Morry

2017-04-01

Full Text Available Oxidative stress, mainly contributed by reactive oxygen species (ROS, has been implicated in pathogenesis of several diseases. We review two primary examples; fibrosis and cancer. In fibrosis, ROS promote activation and proliferation of fibroblasts and myofibroblasts, activating TGF-β pathway in an autocrine manner. In cancer, ROS account for its genomic instability, resistance to apoptosis, proliferation, and angiogenesis. Importantly, ROS trigger cancer cell invasion through invadopodia formation as well as extravasation into a distant metastasis site. Use of antioxidant supplements, enzymes, and inhibitors for ROS-generating NADPH oxidases (NOX is a logical therapeutic intervention for fibrosis and cancer. We review such attempts, progress, and challenges. Lastly, we review how nanoparticles with inherent antioxidant activity can also be a promising therapeutic option, considering their additional feature as a delivery platform for drugs, genes, and imaging agents.

Determining the status of non-transferred embryos in Ireland: a conspectus of case law and implications for clinical IVF practice

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Sills Eric

2009-07-01

Full Text Available Abstract The development of in vitro fertilisation (IVF as a treatment for human infertilty was among the most controversial medical achievements of the modern era. In Ireland, the fate and status of supranumary (non-transferred embryos derived from IVF brings challenges both for clinical practice and public health policy because there is no judicial or legislative framework in place to address the medical, scientific, or ethical uncertainties. Complex legal issues exist regarding informed consent and ownership of embryos, particularly the use of non-transferred embryos if a couple separates or divorces. But since case law is only beginning to emerge from outside Ireland and because legislation on IVF and human embryo status is entirely absent here, this matter is poised to raise contractual, constitutional and property law issues at the highest level. Our analysis examines this medico-legal challenge in an Irish context, and summarises key decisions on this issue rendered from other jurisdictions. The contractual issues raised by the Roche case regarding informed consent and the implications the initial judgment may have for future disputes over embryos are also discussed. Our research also considers a putative Constitutional 'right to procreate' and the implications EU law may have for an Irish case concerning the fate of frozen embryos. Since current Medical Council guidelines are insufficient to ensure appropriate regulation of the advanced reproductive technologies in Ireland, the report of the Commission on Assisted Human Reproduction is most likely to influence embryo custody disputes. Public policy requires the establishment and implementation of a more comprehensive legislative framework within which assisted reproductive medical services are offered.

Respiratory manifestations of panic disorder: causes, consequences and therapeutic implications.

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Sardinha, Aline; Freire, Rafael Christophe da Rocha; Zin, Walter Araújo; Nardi, Antonio Egidio

2009-07-01

Multiple respiratory abnormalities can be found in anxiety disorders, especially in panic disorder (PD). Individuals with PD experience unexpected panic attacks, characterized by anxiety and fear, resulting in a number of autonomic and respiratory symptoms. Respiratory stimulation is a common event during panic attacks. The respiratory abnormality most often reported in PD patients is increased CO2 sensitivity, which has given rise to the hypothesis of fundamental abnormalities in the physiological mechanisms that control breathing in PD. There is evidence that PD patients with dominant respiratory symptoms are more sensitive to respiratory tests than are those who do not manifest such symptoms, and that the former group constitutes a distinct subtype. Patients with PD tend to hyperventilate and to panic in response to respiratory stimulants such as CO2, triggering the activation of a hypersensitive fear network. Although respiratory physiology seems to remain normal in these subjects, recent evidence supports the idea that they present subclinical abnormalities in respiration and in other functions related to body homeostasis. The fear network, composed of the hippocampus, the medial prefrontal cortex, the amygdala and its brain stem projections, might be oversensitive in PD patients. This theory might explain why medication and cognitive-behavioral therapy are both clearly effective. Our aim was to review the relationship between respiration and PD, addressing the respiratory subtype of PD and the hyperventilation syndrome, with a focus on respiratory challenge tests, as well as on the current mechanistic concepts and the pharmacological implications of this relationship.

Therapeutic Uses of Active Videogames: A Systematic Review.

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Staiano, Amanda E; Flynn, Rachel

2014-12-01

Active videogames (AVGs) may be useful for promoting physical activity for therapeutic uses, including for balance, rehabilitation, and management of illness or disease. The literature from 64 peer-reviewed publications that assessed health outcomes of AVGs for therapeutic purposes was synthesized. PubMed, Medline, and PyschInfo were queried for original studies related to the use of AVGs to improve physical outcomes in patients who were ill or undergoing rehabilitation related to balance, burn treatment, cancer, cerebral palsy, Down's syndrome, extremity dysfunction or amputation, hospitalization, lupus, Parkinson's disease, spinal injury, or stroke. The following inclusion criteria were used: (1) human subjects; (2) English language; (3) not duplicates; (4) new empirical data; and (5) tests an AVG, including commercially available or custom-designed. Studies were included regardless of participants' age or the study design. Overall, the vast majority of studies demonstrated promising results for improved health outcomes related to therapy, including significantly greater or comparable effects of AVG play versus usual care. However, many studies were pilot trials with small, homogeneous samples, and many studies lacked a control or comparison group. Some trials tested multiweek or multimonth interventions, although many used a single bout of gameplay, and few included follow-up assessments to test sustainability of improved health. AVGs were acceptable and enjoyable to the populations examined and appear as a promising tool for balance, rehabilitation, and illness management. Future research directions and implications for clinicians are discussed.

The relationship between clinical findings and therapeutic approach in the treatment of fractured frontal sinus walls

Directory of Open Access Journals (Sweden)

Pešić Zoran

2007-01-01

Full Text Available Introduction The incidence of fractured frontal sinus walls vary from 6% to 12% of all craniofacial injuries. Objective Estimated relation between clinical findings and performed therapeutic procedures in treating fractured frontal sinus walls. To estimate success in performed therapeutic procedures, according to the incidence of postoperative complications and the integrity of injured regions from the functional and esthetical aspect. Method We analyzed, by retrospective clinical investigation, 19 patients with fractured frontal sinus walls and dislocated fragments, treated at the Department for Maxillofacial Surgery, Clinic of Dentistry in Niš, in the period March 1995 - March 2006. The success of therapy was estimated based on the incidence and type of complications and esthetical results in relation to preoperative findings. Results Predominant etiological factor in fractures of frontal sinus walls is trauma sustained in traffic accidents, which occurred in 52.6% of patients in our investigation. In clinical findings, the impression was the predominant sign, present in 16 patients. In 6 cases soft tissue access through already present lacerations or their extensions was employed, in 4 cases it was done by supraciliary access and in 9 by bicoronal access. As a therapeutic measure, drainage was performed in 5 cases, cranialisation in one, ostheoneogenetic access in 11 cases and a simple reposition of fragments in 2 patients with fractured frontal sinus walls. Infection as a complication was absent. All patients were satisfied with postoperative esthetical appearance of the injured region. Conclusion The infection, the lacerations and the direction of fractured lines are dominant factors in the determination of therapeutic procedures used to treat fractured frontal sinus walls. This will result in the low incidence of infection as a postoperative complication and in patient’s satisfaction with postoperative esthetical result of the injured

[Nuclear transfer and therapeutic cloning].

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Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

2005-03-01

Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

Therapeutically targeting mitochondrial redox signalling alleviates endothelial dysfunction in preeclampsia.

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McCarthy, Cathal; Kenny, Louise C

2016-09-08

Aberrant placentation generating placental oxidative stress is proposed to play a critical role in the pathophysiology of preeclampsia. Unfortunately, therapeutic trials of antioxidants have been uniformly disappointing. There is provisional evidence implicating mitochondrial dysfunction as a source of oxidative stress in preeclampsia. Here we provide evidence that mitochondrial reactive oxygen species mediates endothelial dysfunction and establish that directly targeting mitochondrial scavenging may provide a protective role. Human umbilical vein endothelial cells exposed to 3% plasma from women with pregnancies complicated by preeclampsia resulted in a significant decrease in mitochondrial function with a subsequent significant increase in mitochondrial superoxide generation compared to cells exposed to plasma from women with uncomplicated pregnancies. Real-time PCR analysis showed increased expression of inflammatory markers TNF-α, TLR-9 and ICAM-1 respectively in endothelial cells treated with preeclampsia plasma. MitoTempo is a mitochondrial-targeted antioxidant, pre-treatment of cells with MitoTempo protected against hydrogen peroxide-induced cell death. Furthermore MitoTempo significantly reduced mitochondrial superoxide production in cells exposed to preeclampsia plasma by normalising mitochondrial metabolism. MitoTempo significantly altered the inflammatory profile of plasma treated cells. These novel data support a functional role for mitochondrial redox signaling in modulating the pathogenesis of preeclampsia and identifies mitochondrial-targeted antioxidants as potential therapeutic candidates.

[Therapeutic effect of cervical Jiaji electroacupuncture on postoperative intractable hiccup of liver neoplasms].

Science.gov (United States)

Zhang, S K; Gao, W B; Liu, Y; He, H

2018-02-23

Objective: To evaluate the therapeutic effect of cervical Jiaji electroacupuncture on postoperative intractable hiccup of liver neoplasms. Methods: A total of 39 patients with postoperative intractable hiccup of liver neoplasms in The First Affiliated Hospital of Heilongjiang University of Chinese Medicine from May 2013 to May 2017 were collected and divided into 2 groups randomly. The electroacupuncture group included 20 cases, the control group included 19 cases. Patients in the electroacupuncture group were treated by cervical Jiaji electroacupuncture (located in C3-5, sympathetic ganglion), while the control group were treated by metoclopramide combined with chlorpromazine for three days. The therapeutic effects of two groups were compared and the onset time were recorded. Results: Total effective rates of electroacupuncture group and control group were 95.0% and 47.4%, respectively. The onset time in electroacupuncture group and control group were (14.8±3.3) h and (30.5±3.1) h, respectively ( P electroacupuncture for 3 days, 6 cases were recovered, 3 cases became better, while 1 case demonstrated no response. No serious adverse reactions were appeared in each group. Conclusion: Cervical Jiaji electroacupuncture is an effective and safe treatment for postoperative intractable hiccup of liver neoplasms, and it can be used as a remedy for intractable hiccup patients who don't respond to drug treatment.

Frontiers in nano-therapeutics

CERN Document Server

Tasnim, Nishat; Sai Krishna, Katla; Kalagara, Sudhakar; Narayan, Mahesh; Noveron, Juan C; Joddar, Binata

2017-01-01

This brief highlights recent research advances in the area of nano-therapeutics. Nanotechnology holds immense potential for application in a wide range of biological and engineering applications such as molecular sensors for disease diagnosis, therapeutic agents for the treatment of diseases, a vehicle for delivering therapeutics and imaging agents for theranostic applications, both in-vitro and in-vivo. The brief is grouped into the following sections namely, A) Discrete Nanosystems ; B) Anisotropic Nanoparticles; C) Nano-films/coated/layered and D) Nano-composites.

Glutathione Redox Control of Asthma: From Molecular Mechanisms to Therapeutic Opportunities

Science.gov (United States)

Jones, Dean P.; Brown, Lou Ann S.

2012-01-01

Abstract Asthma is a chronic inflammatory disorder of the airways associated with airway hyper-responsiveness and airflow limitation in response to specific triggers. Whereas inflammation is important for tissue regeneration and wound healing, the profound and sustained inflammatory response associated with asthma may result in airway remodeling that involves smooth muscle hypertrophy, epithelial goblet-cell hyperplasia, and permanent deposition of airway extracellular matrix proteins. Although the specific mechanisms responsible for asthma are still being unraveled, free radicals such as reactive oxygen species and reactive nitrogen species are important mediators of airway tissue damage that are increased in subjects with asthma. There is also a growing body of literature implicating disturbances in oxidation/reduction (redox) reactions and impaired antioxidant defenses as a risk factor for asthma development and asthma severity. Ultimately, these redox-related perturbations result in a vicious cycle of airway inflammation and injury that is not always amenable to current asthma therapy, particularly in cases of severe asthma. This review will discuss disruptions of redox signaling and control in asthma with a focus on the thiol, glutathione, and reduced (thiol) form (GSH). First, GSH synthesis, GSH distribution, and GSH function and homeostasis are discussed. We then review the literature related to GSH redox balance in health and asthma, with an emphasis on human studies. Finally, therapeutic opportunities to restore the GSH redox balance in subjects with asthma are discussed. Antioxid. Redox Signal. 17, 375–408. PMID:22304503

Rethinking Therapeutic Misconception in Biobanking

DEFF Research Database (Denmark)

Tupasela, Aaro; Snell, Karoliina; Cañada, Jose

2017-01-01

Some authors have noted that in biobank research participants may be guided by what is called therapeutic misconception, whereby participants attribute therapeutic intent to research procedures.This article argues that the notion of therapeutic misconception is increasingly less justified when...... underpinnings for the need to separate research and treatment, and thus the notion of therapeutic misconception in the fi rst place. We call this tension between research and treatment ambivalent research advancement to highlight the difficulties that various actors have in managing such shifts within...

Therapeutic Inertia and Treatment Intensification.

Science.gov (United States)

Josiah Willock, Robina; Miller, Joseph B; Mohyi, Michelle; Abuzaanona, Ahmed; Muminovic, Meri; Levy, Phillip D

2018-01-29

This review aims to emphasize how therapeutic inertia, the failure of clinicians to intensify treatment when blood pressure rises or remains above therapeutic goals, contributes to suboptimal blood pressure control in hypertensive populations. Studies reveal that the therapeutic inertia is quite common and contributes to suboptimal blood pressure control. Quality improvement programs and standardized approaches to support antihypertensive treatment intensification are ways to combat therapeutic inertia. Furthermore, programs that utilize non-physician medical professionals such as pharmacists and nurses demonstrate promise in mitigating the effects of this important problem. Therapeutic inertia impedes antihypertensive management and requires a broad effort to reduce its effects. There is an ongoing need for renewed focus and research in this area to improve hypertension control.

Rocuronium-sugammadex for electroconvulsive therapy management in neuroleptic malignant syndrome: A case report.

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Casas Reza, P; Gestal Vázquez, M; Outeiro Rosato, Á; López Álvarez, S; Diéguez García, P

2017-02-01

Neuroleptics are a group of drugs widely used in the treatment of psychotic symptoms. Among their adverse effects is the ability to trigger a neuroleptic malignant syndrome (NMS). The diagnosis of NMS is determined by exclusion, and its initial therapeutic management should be the withdrawal of neuroleptics, the administration of benzodiazepines, and electroconvulsive therapy (ECT). ECT is an effective treatment in these patients, and in those cases with a poor response to treatment with antipsychotic drugs. A review is presented on the treatment options and anaesthetic implications of ECT used to handle a patient diagnosed with paranoid schizophrenia in the context of NMS. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Security Force Assistance: Cases and Policy

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2018-02-02

theory , cases, and policy implications presented. 3 Methods, Assumptions, and Procedures The analytical narrative method was used to test the...underlying theory --developed separately as a principal-agent model with capacity building in the DwP project. These two cases were chosen as part...the following implications for U.S. national security policy: o Use aid to create incentives , especially via conditionality. Avoid apolitical

Therapeutic Innovations for Targeting Childhood Neuroblastoma: Implications of the Neurokinin-1 Receptor System.

Science.gov (United States)

Berger, Michael; VON Schweinitz, Dietrich

2017-11-01

Neuroblastoma is the most common solid extracranial malignant tumor in children. Despite recent advances in the treatment of this heterogenous tumor with surgery and chemotherapy, the prognosis in advanced stages remains poor. Interestingly, neuroblastoma is one of the few solid tumors, to date, in which an effect for targeted immunotherapy has been proven in controlled clinical trials, giving hope for further advances in the treatment of this and other tumors by targeted therapy. A large array of novel therapeutic options for targeted therapy of neuroblastoma is on the horizon. To this repεrtoirε, the neurokinin-1 receptor (NK1R) system was recently added. The present article explores the most recent developments in targeting neuroblastoma cells via the NK1R and how this new knowledge could be helpful to create new anticancer therapies agains neuroblastoma and other cancers. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Radiation pneumonitis and fibrosis: Mechanisms underlying its pathogenesis and implications for future research

International Nuclear Information System (INIS)

Tsoutsou, Pelagia G.; Koukourakis, Michael I.

2006-01-01

Radiation pneumonitis and subsequent radiation pulmonary fibrosis are the two main dose-limiting factors when irradiating the thorax that can have severe implications for patients' quality of life. In this article, the current concepts about the pathogenetic mechanisms underlying radiation pneumonitis and fibrosis are presented. The clinical course of fibrosis, a postulated acute inflammatory stage, and a late fibrotic and irreversible stage are discussed. The interplay of cells and the wide variety of molecules orchestrating the immunologic response to radiation, their interactions with specific receptors, and the cascade of events they trigger are elucidated. Finally, the implications of this knowledge with respect to the therapeutic interventions are critically presented

Therapeutic Body Wraps in Swiss public adult acute inpatient wards. A retrospective descriptive cohort study.

Science.gov (United States)

Opsommer, E; Dubois, J; Bangerter, G; Panchaud, R; Martin, D; Skuza, K

2016-04-01

WHAT IS KNOWN ON THE SUBJECT?: Various expert opinions reported relational benefits and tranquilizing effects of therapeutic body wraps (TBW) in adults experiencing high anxiety in the context of psychosis. Yet, this tranquilizing effect was never investigated in larger samples and in the context of modern psychopharmacology. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This is the first study to establish descriptive statistics of this mind-body therapy in French-speaking Switzerland where TBWs are routinely used in two public psychiatric hospitals. It brings knowledge on patients nowadays treated with TBW. Moreover, it opens a new area of investigation on the potential of this nursing technique, which may contribute to reduce anxiolytic medication in severely ill patients. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: This study sheds light on a clinical practice in mental health nursing and upon nurses' specific contribution to psychiatric clinic. It investigates a potential for TBWs to reduce the use of anxiolytic medications by patients who agreed to have TBW as part of their treatment. It may help to inform the mental health nursing practice. Introduction Many patients suffering from serious mental illness experience severe anxiety and those with psychosis often report the feeling of their bodies falling apart. While it is believed that these patients benefit from therapeutic body wraps (TBWs), the use of this adjunct therapy has rarely been studied in adult patients. Aims The aim of this study was to obtain descriptive statistics on the clinical, social-demographic and institutional reality of TBW therapy in Swiss public adult inpatient wards. Methods Retrospective data related to a cohort of 172 adult inpatients were retrieved from records of two public hospitals. Correlations between TBW and the prescriptions of lorazepam were explored. Results TBWs were primarily used for patients diagnosed with either schizophrenia, schizotypal, delusional and other non

Implications of the 750 GeV γγ resonance as a case study for the International Linear Collider

International Nuclear Information System (INIS)

Fujii, Keisuke; Grojean, Christophe; Univ. Autonoma de Barcelon; Peskin, Michael E.

2016-07-01

If the γγ resonance at 750 GeV suggested by 2015 LHC data turns out to be a real effect, what are the implications for the physics case and upgrade path of the International Linear Collider? Whether or not the resonance is confirmed, this question provides an interesting case study testing the robustness of the ILC physics case. In this note, we address this question with two points: (1) Almost all models proposed for the new 750 GeV particle require additional new particles with electroweak couplings. The key elements of the 500 GeV ILC physics program - precision measurements of the Higgs boson, the top quark, and 4-fermion interactions - will powerfully discriminate among these models. This information will be important in conjunction with new LHC data, or alone, if the new particles accompanying the 750 GeV resonance are beyond the mass reach of the LHC. (2) Over a longer term, the energy upgrade of the ILC to 1 TeV already discussed in the ILC TDR will enable experiments in γγ and e"+e"- collisions to directly produce and study the 750 GeV particle from these unique initial states.

Implications of the 750 GeV γγ Resonance as a Case Study for the International Linear Collider

Energy Technology Data Exchange (ETDEWEB)

Fujii, Keisuke [High Energy Accelerator Research Organization (KEK), Tsukuba (Japan); Grojean, Christophe [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Univ. Autonoma de Barcelona (Spain). Inst. Catalana de Recerca i Estudis Avancats (ICREA) and Inst. de Fisica d' Altes Energies (IFAE); Peskin, Michael E. [SLAC National Accelerator Lab., Menlo Park, CA (United States); Barklow, Tim [SLAC National Accelerator Lab., Menlo Park, CA (United States); Gao, Yuanning [Tsinghua Univ., Beijing (China). Center for High Energy Physics; Kanemura, Shinya [Univ. of Toyama (Japan). Dept. of Physics; Kim, Hyungdo [Seoul National Univ. (Korea, Republic of). Dept. of Physics and Astronomy; List, Jenny [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Nojiri, Mihoko [High Energy Accelerator Research Organization (KEK), Tsukuba (Japan); Univ. of Tokyo (Japan). Kavli Inst. for the Physics and Mathematics of the Universe; Perelstein, Maxim [Cornell Univ., Ithaca, NY (United States). Lab. for Elementary Particle Physics; Poschl, Roman [Univ. Paris-Sud, Orsay (France). Linear Accelerator Lab. (LAL). Centre Scientifique d' Orsay; Reuter, Jurgen [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Simon, Frank [Max Planck Inst. for Physics (MPP), Munich (Germany); Tanabe, Tomohiko [Univ. of Tokyo (Japan). International Center for Elementary Particle Physics (ICEPP); Yu, Jaehoon [Univ. of Texas, Arlington, TX (United States). Dept. of Physics; Wells, James D. [Univ. of Michigan, Ann Arbor, MI (United States). Michigan Center for Theoretical Physics; Falkowski, Adam [Univ. Paris-Sud, Orsay (France). Lab. of Theoretical Physics (LPT); Matsumoto, Shigeki [Univ. of Tokyo (Japan). Kavli Inst. for the Physics and Mathematics of the Universe; Moroi, Takeo [Univ. of Tokyo (Japan). Dept. of Physics; Richard, Francois [Univ. Paris-Sud, Orsay (France). Linear Accelerator Lab. (LAL). Centre Scientifique d' Orsay; Tian, Junping [Univ. of Tokyo (Japan). International Center for Elementary Particle Physics (ICEPP); Vos, Marcel [Spanish National Research Council (CSIC), Valencia (Spain) and Univ. of Valencia (Spain). Inst. for Corpuscular Physics (IFIC); Yokoya, Hiroshi [Korean Inst. for Advanced Study (KIAS), Seoul (Korea, Republic of ). Quantum Universe Center; Murayama, Hitoshi [Univ. of Tokyo (Japan). Kavli Inst. for the Physics and Mathematics of the Universe; Univ. of California, Berkeley, CA (United States). Dept. of Physics; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Yamamoto, Hitoshi [Tohoku Univ., Sendai (Japan). Dept. of Physics

2016-07-14

If the γγ resonance at 750 GeV suggested by 2015 LHC data turns out to be a real effect, what are the implications for the physics case and upgrade path of the International Linear Collider? Whether or not the resonance is confirmed, this question provides an interesting case study testing the robustness of the ILC physics case. In this note, we address this question with two points: (1) Almost all models proposed for the new 750 GeV particle require additional new particles with electroweak couplings. The key elements of the 500 GeV ILC physics program - precision measurements of the Higgs boson, the top quark, and 4-fermion interactions - will powerfully discriminate among these models. This information will be important in conjunction with new LHC data, or alone, if the new particles accompanying the 750 GeV resonance are beyond the mass reach of the LHC. (2) Over a longer term, the energy upgrade of the ILC to 1 TeV already discussed in the ILC TDR will enable experiments in γγ and e⁺e^- collisions to directly produce and study the 750 GeV particle from these unique initial states.

Structured Therapeutic Games for Nonoffending Caregivers of Children Who Have Experienced Sexual Abuse.

Science.gov (United States)

Springer, Craig I; Colorado, Giselle; Misurell, Justin R

2015-01-01

Game-based cognitive-behavioral therapy group model for nonoffending caregivers utilizes structured therapeutic games to assist parents following child sexual abuse. Game-based cognitive-behavioral therapy group model is a manualized group treatment approach that integrates evidence-based cognitive-behavioral therapy components with structured play therapy to teach parenting and coping skills, provide psychoeducation, and process trauma. Structured therapeutic games were designed to allow nonoffending caregivers to process their children's abuse experiences and learn skills necessary to overcome trauma in a nonthreatening, fun, and engaging manner. The implementation of these techniques allow clinicians to address a variety of psychosocial difficulties that are commonly found among nonoffending caregivers of children who have experienced sexual abuse. In addition, structured therapeutic games help caregivers develop strengths and abilities that they can use to help their children cope with abuse and trauma and facilitates the development of positive posttraumatic growth. Techniques and procedures for treatment delivery along with a description of core components and therapeutic modules are discussed. An illustrative case study is provided.

Synchrony in Psychotherapy: A Review and an Integrative Framework for the Therapeutic Alliance

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Koole, Sander L.; Tschacher, Wolfgang

2016-01-01

During psychotherapy, patient and therapist tend to spontaneously synchronize their vocal pitch, bodily movements, and even their physiological processes. In the present article, we consider how this pervasive phenomenon may shed new light on the therapeutic relationship– or alliance– and its role within psychotherapy. We first review clinical research on the alliance and the multidisciplinary area of interpersonal synchrony. We then integrate both literatures in the Interpersonal Synchrony (In-Sync) model of psychotherapy. According to the model, the alliance is grounded in the coupling of patient and therapist’s brains. Because brains do not interact directly, movement synchrony may help to establish inter-brain coupling. Inter-brain coupling may provide patient and therapist with access to another’s internal states, which facilitates common understanding and emotional sharing. Over time, these interpersonal exchanges may improve patients’ emotion-regulatory capacities and related therapeutic outcomes. We discuss the empirical assessment of interpersonal synchrony and review preliminary research on synchrony in psychotherapy. Finally, we summarize our main conclusions and consider the broader implications of viewing psychotherapy as the product of two interacting brains. PMID:27378968

Synchrony in Psychotherapy: A Review and an Integrative Framework for the Therapeutic Alliance.

Science.gov (United States)

Koole, Sander L; Tschacher, Wolfgang

2016-01-01

During psychotherapy, patient and therapist tend to spontaneously synchronize their vocal pitch, bodily movements, and even their physiological processes. In the present article, we consider how this pervasive phenomenon may shed new light on the therapeutic relationship- or alliance- and its role within psychotherapy. We first review clinical research on the alliance and the multidisciplinary area of interpersonal synchrony. We then integrate both literatures in the Interpersonal Synchrony (In-Sync) model of psychotherapy. According to the model, the alliance is grounded in the coupling of patient and therapist's brains. Because brains do not interact directly, movement synchrony may help to establish inter-brain coupling. Inter-brain coupling may provide patient and therapist with access to another's internal states, which facilitates common understanding and emotional sharing. Over time, these interpersonal exchanges may improve patients' emotion-regulatory capacities and related therapeutic outcomes. We discuss the empirical assessment of interpersonal synchrony and review preliminary research on synchrony in psychotherapy. Finally, we summarize our main conclusions and consider the broader implications of viewing psychotherapy as the product of two interacting brains.

Full recovery two months after therapeutic hypothermia following cardiopulmonary resuscitation in a patient with out-of-hospital cardiac arrest

International Nuclear Information System (INIS)

Ahn, J.; Cha, K.S.; Oh, J.H.; Lee, H.C.

2013-01-01

Neurologic impairments are very common among patients who get a recovery of spontaneous circulation after suffering from out-of-hospital cardiac arrest. Therapeutic hypothermia is established as a standardized therapeutic strategy for those patients in whom it decreases mortality rate and improves neurologic outcome. Herein, we report a case of patient who experienced out-of-hospital cardiac arrest with ischaemic heart disease and ventricular arrhythmia and got a full recovery without any neurologic impediments 2 months after being managed with therapeutic hypothermia. (author)

Implications for Therapeutic Intervention

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A. L. Hof

2001-01-01

Full Text Available Patients with an upper motor neurone syndrome (CP suffer from many disabling primary symptoms: spasms, weakness, and loss of dexterity. These primary ‘neurogenic’ symptoms often lead to secondary disabilities, muscle contractures, and tertiary effects, bone deformations. A common symptom of CP is hypertonia, with. the consequence that the involved muscles remain in an excessively shortened length for most of the time. As a normal reaction of the muscle tissue, the number of sarcomeres is reduced and the muscle fibers shorten permanently: a contracture develops. A possible second type of contracture is that normal muscle lengthening along with bone growth is affected. Current treatments for the secondary effects include (1 reduction of muscle force, (2lengthening of the muscle fibers by serial plaster casts, and (3surgical lengthening of tendons or aponeurosis. The choice of treatment depends on the cause of the functional deficit. Bone tissue also adapts itself to abnormal forces, especially in the growth period. The hypertonias or contractures of CP so may give rise to bone malformations that interfere with function (e.g. femur endorotation or may reduce the action of muscles by changing the lever arm (e.g. ankle varus. Although prevention should always be preferred, a timely surgical intervention cannot always be avoided. The differences in treatment for the various groups require and justify an extensive laboratory investigation, including EMG recordings in gait, measurement of passive elastic properties, and long-term observation of the hypertonia.

[Hyperfunctioning thyroid carcinoma. Description of a case].

Science.gov (United States)

Pandolfi, C; Colecchia, M; Gianini, A

1997-09-01

Differentiated thyroid cancers account for 1% of all neoplasias but only for 2.3% of thyroid nodules. A particular condition is represented by the association with hyperthyroidism, which is found in about 7% of cases. Even more rarely may be themselves cause of thyrotoxicosis. In the present paper, the case of a 66-year old male patient, bearing a recently appeared goiter, referred to us for suspicion of lung cancer and hyperthyroid symptoms, is reported. Among appropriate investigations, the finding of high titer of thyroglobulin in the aspiration needle and cytology examination suggested that thyroid lesion was primary and not metastatic, while scintiscan with J-131 isotope showed that excess of thyroid hormones was just due to it; histological diagnosis was of papillary carcinoma. As to the pathogenesis of the neoplasma during hyperthyroidism, a causal role of thyroid stimulating auto-antibodies has been suggested in the cases associated with Graves' disease, absent in our patient, which could elicitate cancer progression in the mean time. Interestingly, activating mutation of thyroid hormone receptor (TSH-r) gene has been demonstrated in a hyperfunctioning differentiated cancer. Notwithstanding the unexpected clinical behaviour may appear very rare, molecular biology studies on aspiration biopsies (FNAB) will allow, in the future, to better define the neoplastic nature of some hot nodules. In personal opinion, this particular pathology must be attently searched both for its implications in the prognosis and therapeutic strategy and because it could be less rare than generally considered up to now.

Implications of central immune signaling caused by drugs of abuse: mechanisms, mediators and new therapeutic approaches for prediction and treatment of drug dependence.

Science.gov (United States)

Coller, Janet K; Hutchinson, Mark R

2012-05-01

In the past two decades a trickle of manuscripts examining the non-neuronal central nervous system immune consequences of the drugs of abuse has now swollen to a significant body of work. Initially, these studies reported associative evidence of central nervous system proinflammation resulting from exposure to the drugs of abuse demonstrating key implications for neurotoxicity and disease progression associated with, for example, HIV infection. However, more recently this drug-induced activation of central immune signaling is now understood to contribute substantially to the pharmacodynamic actions of the drugs of abuse, by enhancing the engagement of classical mesolimbic dopamine reward pathways and withdrawal centers. This review will highlight the key in vivo animal, human, biological and molecular evidence of these central immune signaling actions of opioids, alcohol, cocaine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). Excitingly, this new appreciation of central immune signaling activity of drugs of abuse provides novel therapeutic interventions and opportunities to identify 'at risk' individuals through the use of immunogenetics. Discussion will also cover the evidence of modulation of this signaling by existing clinical and pre-clinical drug candidates, and novel pharmacological targets. Finally, following examination of the breadth of central immune signaling actions of the drugs of abuse highlighted here, the current known common immune signaling components will be outlined and their impact on established addiction neurocircuitry discussed, thereby synthesizing a common neuroimmune hypothesis of addiction. Copyright © 2012 Elsevier Inc. All rights reserved.

Therapeutic ultrasound - Exciting applications and future challenges

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Saffari, Nader

2018-04-01

This paper presents an overview of the applications of ultrasound for the treatment of an ever-growing range of medical conditions. After presenting a brief history of the development of therapeutic ultrasound, the different mechanisms by which beneficial bio-effects are triggered will be discussed. This will be followed by a discussion of some of the more promising applications, some of which have already been licensed and introduced into the clinic. The case of liver tumour ablation will be discussed to demonstrate some of the engineering challenges that still need to be overcome before this technology finds wider uptake in the medical world.

How a Fully Automated eHealth Program Simulates Three Therapeutic Processes: A Case Study.

Science.gov (United States)

Holter, Marianne T S; Johansen, Ayna; Brendryen, Håvar

2016-06-28

eHealth programs may be better understood by breaking down the components of one particular program and discussing its potential for interactivity and tailoring in regard to concepts from face-to-face counseling. In the search for the efficacious elements within eHealth programs, it is important to understand how a program using lapse management may simultaneously support working alliance, internalization of motivation, and behavior maintenance. These processes have been applied to fully automated eHealth programs individually. However, given their significance in face-to-face counseling, it may be important to simulate the processes simultaneously in interactive, tailored programs. We propose a theoretical model for how fully automated behavior change eHealth programs may be more effective by simulating a therapist's support of a working alliance, internalization of motivation, and managing lapses. We show how the model is derived from theory and its application to Endre, a fully automated smoking cessation program that engages the user in several "counseling sessions" about quitting. A descriptive case study based on tools from the intervention mapping protocol shows how each therapeutic process is simulated. The program supports the user's working alliance through alliance factors, the nonembodied relational agent Endre and computerized motivational interviewing. Computerized motivational interviewing also supports internalized motivation to quit, whereas a lapse management component responds to lapses. The description operationalizes working alliance, internalization of motivation, and managing lapses, in terms of eHealth support of smoking cessation. A program may simulate working alliance, internalization of motivation, and lapse management through interactivity and individual tailoring, potentially making fully automated eHealth behavior change programs more effective.

"Too stubborn to ever be governed by enforced insanity": Some therapeutic jurisprudence dilemmas in the representation of criminal defendants in incompetency and insanity cases.

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Perlin, Michael L

2010-01-01

Little attention has been paid to the importance of the relationship between therapeutic jurisprudence (TJ) and the role of criminal defense lawyers in insanity and incompetency-to-stand-trial (IST) cases. That inattention is especially noteworthy in light of the dismal track record of counsel providing services to defendants who are part of this cohort of incompetency-status-raisers and insanity-defense-pleaders. On one hand, this lack of attention is a surprise as TJ scholars have, in recent years, turned their attention to virtually every other aspect of the legal system. On the other hand, it is not a surprise, given the omnipresence of sanism, an irrational prejudice of the same quality and character of other irrational prejudices that cause (and are reflected in) prevailing social attitudes of racism, sexism, homophobia, and ethnic bigotry, that infects both our jurisprudence and our lawyering practices. Sanism is largely invisible and largely socially acceptable, and is based predominantly upon stereotype, myth, superstition, and deindividualization. It is sustained and perpetuated by our use of alleged "ordinary common sense" (OCS) and heuristic reasoning in an unconscious response to events both in everyday life and in the legal process. This paper examines the literature that seeks to apply TJ principles to the criminal law process in general, drawing mostly on the work of Professor David Wexler. It considers why the lack of attention that I have referred to already is surprising (given TJ's mandate and the fact that many TJ issues are inevitably raised in any insanity or IST case). The paper then considers why this lack of attention is not surprising, given the omnipresence of sanism. It will consider some of the actual counseling issues that might arise in these contexts, and offer some suggestions to lawyers representing clients in cases in which mental status issues may be raised. The paper concludes that we must rigorously apply therapeutic

The Implications of Cancer Stem Cells for Cancer Therapy

Directory of Open Access Journals (Sweden)

Wenjing Jiang

2012-12-01

Full Text Available Surgery, radiotherapy and chemotherapy are universally recognized as the most effective anti-cancer therapies. Despite significant advances directed towards elucidating molecular mechanisms and developing clinical trials, cancer still remains a major public health issue. Recent studies have showed that cancer stem cells (CSCs, a small subpopulation of tumor cells, can generate bulk populations of nontumorigenic cancer cell progeny through the self-renewal and differentiation processes. As CSCs are proposed to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors, development of CSC-targeted therapeutic strategies holds new hope for improving survival and quality of life in patients with cancer. Therapeutic innovations will emerge from a better understanding of the biology and environment of CSCs, which, however, are largely unexplored. This review summarizes the characteristics, evidences and development of CSCs, as well as implications and challenges for cancer treatment.

Corrective interpersonal experience in psychodrama group therapy: a comprehensive process analysis of significant therapeutic events.

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McVea, Charmaine S; Gow, Kathryn; Lowe, Roger

2011-07-01

This study investigated the process of resolving painful emotional experience during psychodrama group therapy, by examining significant therapeutic events within seven psychodrama enactments. A comprehensive process analysis of four resolved and three not-resolved cases identified five meta-processes which were linked to in-session resolution. One was a readiness to engage in the therapeutic process, which was influenced by client characteristics and the client's experience of the group; and four were therapeutic events: (1) re-experiencing with insight; (2) activating resourcefulness; (3) social atom repair with emotional release; and (4) integration. A corrective interpersonal experience (social atom repair) healed the sense of fragmentation and interpersonal disconnection associated with unresolved emotional pain, and emotional release was therapeutically helpful when located within the enactment of this new role relationship. Protagonists who experienced resolution reported important improvements in interpersonal functioning and sense of self which they attributed to this experience.

Human Factor in Therapeutic Relationship

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Ramazan Akdogan

2011-03-01

Full Text Available herapeutic relationship is a professional relationship that has been structured based on theoretical props. This relationship is a complicated, wide and unique relationship which develops between two people, where both sides' personality and attitudes inevitably interfere. Therapist-client relationship experienced through transference and counter transference, especially in psychodynamic approaches, is accepted as the main aspect of therapeutic process. However, the approaches without dynamic/deterministic tendency also take therapist-client relationship into account seriously and stress uniqueness of interaction between two people. Being a person and a human naturally sometimes may negatively influence the relationship between the therapist and client and result in a relationship going out of the theoretical frame at times. As effective components of a therapeutic process, the factors that stem from being human include the unique personalities of the therapist and the client, their values and their attitude either made consciously or subconsciously. Literature has shown that the human-related factors are too effective to be denied in therapeutic relationship process. Ethical and theoretical knowledge can be inefficient to prevent the negative effects of these factors in therapeutic process at which point a deep insight and supervision would have a critical role in continuing an acceptable therapeutic relationship. This review is focused on the reflection of some therapeutic factors resulting from being human and development of counter transference onto the therapeutic process.

Regulatory roles and therapeutic potential of microRNA in sarcoma.

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Lim, Hui Jun; Yang, Jia-Lin

2016-01-01

MicroRNAs (miRNAs) are single-stranded noncoding RNAs involved in various biological processes, including cell differentiation and development. They play multiple key roles as tumour suppressors, oncogenes or both in particular cases. This review aims to summarise current findings of the expression of miRNAs and their role in clinical oncology. Current knowledge regarding the involvement of miRNAs in different sarcoma subtypes will be assessed, in conjunction with their potential application as therapeutic targets. Relevant articles in scientific databases were identified using a combination of search terms, including "microRNA," "deregulation," "sarcoma," and "targeted therapy". These databases included Medline, Embase, Cochrane Review, Pubmed and Scopus. Aberrant miRNA expression patterns have been identified in a range of sarcoma subtypes, and differences in miRNA expression profiles between malignant cells and their normal counterparts suggests that miRNAs play key roles in sarcoma development. The identification of unique miRNA patterns in individual tumour types could possibly be used as a diagnostic tool in sarcoma. Moreover, identification of these miRNAs provides novel targets for the development of therapeutic strategies in distinct sarcoma subtypes. miRNAs hold significant potential as diagnostic biomarkers, as well as therapeutic targets in sarcoma. Possible future clinical applications include the use of miRNA pathways as therapeutic targets or miRNA expression profiling as a means of patient selection. The involvement miRNAs will undoubtedly contribute to the advancement of future targeted therapeutic interventions in sarcoma, and further establishment of appropriate delivery systems is vital for their use in clinical settings. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Translational nanomedicine--through the therapeutic window.

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Pierce, Robin L

2015-01-01

Translational nanomedicine occurs only through the successful integration of multiple inputs and iterative modifications. The therapeutic window plays a pivotal role in the trajectory of translational nanomedicine. Often defined in terms of the range of dosage for safe and effective therapeutic effect, a second definition of the therapeutic window refers to the often narrow temporal window in which a therapeutic effect can be obtained. Expanding the second definition to explicitly include the spatial dimension, this article explores aspects of the therapeutic spaces created by nanomedicine that shift the traditional dimensions of symptom, sign and pathology. This article analyzes three aspects of the therapeutic window in nanomedicine - temporal, spatial and manner of construction and their impact on the dimensions of modern medicine.

Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches.

Science.gov (United States)

Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D

2015-01-01

The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis.

Therapeutic enhancement: nursing intervention category for patients diagnosed with Readiness for Therapeutic Regimen Management.

Science.gov (United States)

Kelly, Cynthia W

2008-04-01

To present a new nursing intervention category called therapeutic enhancement. Fewer than half of North Americans follow their physician's recommendations for diet and exercise, even when such are crucial to their health or recovery. It is imperative that nurses consider new ways to promote healthy behaviours. Therapeutic enhancement is intended to provide such a fresh approach. Traditional intervention techniques focusing on education, contracts, social support and more frequent interaction with physicians appear not to be effective when used alone. Successful strategies have been multidisciplinary; and have included interventions by professional nurses who assist patients to understand their disease and the disease process and that helps them to develop disease-management and self-management skills. Therapeutic enhancement incorporates The Stages of Change Theory, Commitment to Health Theory, Motivational Interviewing techniques and instrumentation specifically designed for process evaluation of health-promoting interventions. This is a critical review of approaches that, heretofore, have not been synthesised in a single published article. Based on the commonly used Stages of Change model, therapeutic enhancement is useful for patients who are at the action stage of change. Using therapeutic enhancement as well as therapeutic strategies identified in Stages of Change Theory, such as contingency management, helping relationships, counterconditioning, stimulus control and Motivational Interviewing techniques, nursing professionals can significantly increase the chances of patients moving from action to the maintenance stage of change for a specific health behaviour. Using the nursing intervention category, therapeutic enhancement can increase caregivers' success in helping patients maintain healthy behaviours.

The therapeutic relationship after psychiatric admission.

LENUS (Irish Health Repository)

Roche, Eric

2014-03-01

The therapeutic relationship is one of the most central and important factors in the treatment of mental health disorders. A better therapeutic relationship is associated with service engagement, medication adherence, and satisfaction with services. This study aimed to compare the demographic and clinical factors associated with the therapeutic relationship in voluntarily and involuntarily admitted psychiatric service users. We found that individuals who had been admitted involuntarily, who had a diagnosis of a psychotic disorder, and who reported higher levels of perceived pressures on admission were more likely to have a poorer therapeutic relationship with their consultant psychiatrist. Greater levels of insight and treatment satisfaction, together with higher levels of procedural justice experienced on admission, were associated with a better therapeutic relationship. We found that the level of perceived coercion on admission was not related to the therapeutic relationship. Targeted interventions to improve the therapeutic relationship, particularly for involuntarily admitted service users, are discussed.

Atropa belladonna neurotoxicity: Implications to neurological disorders.

Science.gov (United States)

Kwakye, Gunnar F; Jiménez, Jennifer; Jiménez, Jessica A; Aschner, Michael

2018-06-01

Atropa belladonna, commonly known as belladonna or deadly nightshade, ranks among one of the most poisonous plants in Europe and other parts of the world. The plant contains tropane alkaloids including atropine, scopolamine, and hyoscyamine, which are used as anticholinergics in Food and Drug Administration (FDA) approved drugs and homeopathic remedies. These alkaloids can be very toxic at high dose. The FDA has recently reported that Hyland's baby teething tablets contain inconsistent amounts of Atropa belladonna that may have adverse effects on the nervous system and cause death in children, thus recalled the product in 2017. A greater understanding of the neurotoxicity of Atropa belladonna and its modification of genetic polymorphisms in the nervous system is critical in order to develop better treatment strategies, therapies, regulations, education of at-risk populations, and a more cohesive paradigm for future research. This review offers an integrated view of the homeopathy and neurotoxicity of Atropa belladonna in children, adults, and animal models as well as its implications to neurological disorders. Particular attention is dedicated to the pharmaco/toxicodynamics, pharmaco/toxicokinetics, pathophysiology, epidemiological cases, and animal studies associated with the effects of Atropa belladonna on the nervous system. Additionally, we discuss the influence of active tropane alkaloids in Atropa belladonna and other similar plants on FDA-approved therapeutic drugs for treatment of neurological disorders. Copyright © 2018. Published by Elsevier Ltd.

Neoadjuvant Therapy in Patients with Pancreatic Cancer: A Disappointing Therapeutic Approach?

International Nuclear Information System (INIS)

Zimmermann, Carolin; Folprecht, Gunnar; Zips, Daniel; Pilarsky, Christian; Saeger, Hans Detlev; Grutzmann, Robert

2011-01-01

Pancreatic cancer is a devastating disease. It is the fourth leading cause of cancer-related death in Germany. The incidence in 2003/2004 was 16 cases per 100.000 inhabitants. Of all carcinomas, pancreatic cancer has the highest mortality rate, with one- and five-year survival rates of 25% and less than 5%, respectively, regardless of the stage at diagnosis. These low survival rates demonstrate the poor prognosis of this carcinoma. Previous therapeutic approaches including surgical resection combined with adjuvant therapy or palliative chemoradiation have not achieved satisfactory results with respect to overall survival. Therefore, it is necessary to evaluate new therapeutic approaches. Neoadjuvant therapy is an interesting therapeutic option for patients with pancreatic cancer. For selected patients with borderline or unresectable disease, neoadjuvant therapy offers the potential for tumor downstaging, increasing the probability of a margin-negative resection and decreasing the occurrence of lymph node metastasis. Currently, there is no universally accepted approach for treating patients with pancreatic cancer in the neoadjuvant setting. In this review, the most common neoadjuvant strategies will be described, compared and discussed

Therapeutic Engagement as a Predictor of Retention in Adolescent Therapeutic Community Treatment

Science.gov (United States)

Abdel-Salam, Sami; Gunter, Whitney D.

2014-01-01

The adolescent drug problem places a huge toll on society and a heavy burden on the criminal justice system. Research regarding the benefits of therapeutic community (TC) treatment for adolescents has shown it to be effective. Despite the ability of therapeutic communities to lower drug relapse and reduce criminality, a great deal remains unknown…

Therapeutic and post-lesional aspects of enzootic pneumonia in pigs

Directory of Open Access Journals (Sweden)

Adrian C. Stancu

2013-05-01

Full Text Available The mycoplasmas are causing significant economic damage, these conditions being constant attention of farmers and veterinary services. Economic losses may be due to mortality, veterinary restrictions, a decrease in meat production, increased feed consumption and expenditure specific therapeutic and control measures. The conducted reaserches aimed at methods of disease treatment and diagnosis of enzootic pneumonia based on morphopathological lesions (macroscopic and histopathologicalin dead pigs cases.

Insomnia in childhood and adolescence: clinical aspects, diagnosis, and therapeutic approach

Directory of Open Access Journals (Sweden)

Magda Lahorgue Nunes

2015-11-01

Conclusions: Insomnia complaints in children and adolescents should be taken into account and appropriately investigated by the pediatrician, considering the association with several comorbidities, which must also be diagnosed. The main causes of insomnia and triggering factors vary according to age and development level. The therapeutic approach must include sleep hygiene and behavioral techniques and, in individual cases, pharmacological treatment.

Tetrodotoxin (TTX as a Therapeutic Agent for Pain

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Cruz Miguel Cendán

2012-01-01

Full Text Available Tetrodotoxin (TTX is a potent neurotoxin that blocks voltage-gated sodium channels (VGSCs. VGSCs play a critical role in neuronal function under both physiological and pathological conditions. TTX has been extensively used to functionally characterize VGSCs, which can be classified as TTX-sensitive or TTX-resistant channels according to their sensitivity to this toxin. Alterations in the expression and/or function of some specific TTX-sensitive VGSCs have been implicated in a number of chronic pain conditions. The administration of TTX at doses below those that interfere with the generation and conduction of action potentials in normal (non-injured nerves has been used in humans and experimental animals under different pain conditions. These data indicate a role for TTX as a potential therapeutic agent for pain. This review focuses on the preclinical and clinical evidence supporting a potential analgesic role for TTX. In addition, the contribution of specific TTX-sensitive VGSCs to pain is reviewed.

Therapeutic Effect of 131I for 230 Patients with Hyperthyroidism

International Nuclear Information System (INIS)

He Yujie; Zhang Chengxi; Hu Jiqing; Guo Sihui; Yuan Hui; Li Jing

2009-01-01

To evaluate the therapeutic effect of 131 I in treatment of patients with hyperthyroidism and analysis the factors that influence the effect, 230 cases of hyperthyroidism were treated with 131 I, and were followed-up at 1.5, 3, 6, 12 months and even longer time after 131 I radiotherapy. The serum levels of FT3, FT4 and TSH were detected in all cases. The results showed that 181 patients were cured (78.6%), 22 patients were improved (9.5%), 23 cases developed early hypothyroidism(10.0%),and 4 cases developed later hypothyroidism. 12 cases in 27 patients with hypothyroidism treated with thyroxin were recovered, but the other 15 cases need to be given permanent treatment. The factors which influence 131 I radiotherapeutic effect include the patient age, course of disease,application of ATD, size and quality of thyroid, and the level of thyroid hormone. The patients should be followed up to prevent occurrence of hypothyroidism. The early hypothyroidism should be treated in order to decrease the permanent hypothyroidism rate. (authors)

Everolimus Implicated in Case of Severe Gastrointestinal Hemorrhage

Directory of Open Access Journals (Sweden)

Paul Gonzales

2017-01-01

Full Text Available Breast cancer remains the leading cause of cancer and the third leading cause of cancer related deaths among our population with an estimated number of 246,660 new cases and 40,450 deaths in 2016. With treatment advancements, including targeted agents such as Everolimus, a mammalian target of rapamycin (mTOR inhibitor, survivability and quality of life continue to improve. However, with the use of these agents come adverse effects, some of which are still being characterized. Our case demonstrates recurrent episodes of gastrointestinal bleeding in a 60-year-old woman being treated with Everolimus for progressive metastatic breast cancer. On endoscopy, bleeding was secondary to erosive gastritis. Previous case reports have described bleeding due to gastric antral vascular ectasia (GAVE, which was described in two prior reported cases. In our case, bleeding also occurred on a reduced dose of Everolimus compared to what is previously reported (5 mg versus 10 mg. As a result of her gastrointestinal bleeding, she required multiple endoscopic interventions including argon plasma coagulation and multipolar heater probe to achieve hemostasis. This is the first case reported of gastrointestinal bleeding not consistent with GAVE and occurring while being on a reduced dose of Everolimus. It is important to document our case so that the Gastroenterology and Hematology communities can be educated and made aware for their patient populations on Everolimus.

[Health security--GMOs in therapeutics].

Science.gov (United States)

Trouvin, J-H

2003-03-01

The recent progress in human therapeutics has been made possible thanks to molecular biology and its use in producing proteins having the same sequence and structure as that of human proteins. The use of GMOs allows production of proteins with high added value in therapeutics, which are of satisfactory quality. GMOs may also be directly administered to patients as gene therapy vectors. However, the use of GMOs in therapeutics must take into consideration some risks, particularly those of microbiological contamination, of neo-antigenicity as well as environmental risks with regard to the way of use of the GMO. Nevertheless, those risks are taken in due consideration in the development of these new medicinal products; solutions have been found to allow their use in therapeutics with a very positive benefit/risk ratio. Medicinal products from biotechnology have enabled considerable therapeutic progress without compromising health security.

Cell-derived microparticles: new targets in the therapeutic management of disease.

Science.gov (United States)

Roseblade, Ariane; Luk, Frederick; Rawling, Tristan; Ung, Alison; Grau, Georges E R; Bebawy, Mary

2013-01-01

Intercellular communication is essential to maintain vital physiological activities and to regulate the organism's phenotype. There are a number of ways in which cells communicate with one another. This can occur via autocrine signaling, endocrine signaling or by the transfer of molecular mediators across gap junctions. More recently communication via microvesicular shedding has gained important recognition as a significant pathway by which cells can coordinate the spread and dominance of selective traits within a population. Through this communication apparatus, cells can now acquire and secure a survival advantage, particularly in the context of malignant disease. This review aims to highlight some of the functions and implications of microparticles in physiology of various disease states, and present a novel therapeutic strategy through the regulation of microparticle production.

Therapeutic cloning: The ethical limits

International Nuclear Information System (INIS)

Whittaker, Peter A.

2005-01-01

A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparing immunocompatible pluripotent stem cells are indicated

Therapeutic cloning in the mouse

Science.gov (United States)

Mombaerts, Peter

2003-01-01

Nuclear transfer technology can be applied to produce autologous differentiated cells for therapeutic purposes, a concept termed therapeutic cloning. Countless articles have been published on the ethics and politics of human therapeutic cloning, reflecting the high expectations from this new opportunity for rejuvenation of the aging or diseased body. Yet the research literature on therapeutic cloning, strictly speaking, is comprised of only four articles, all in the mouse. The efficiency of derivation of embryonic stem cell lines via nuclear transfer is remarkably consistent among these reports. However, the efficiency is so low that, in its present form, the concept is unlikely to become widespread in clinical practice. PMID:12949262

Could Nutritional Rehabilitation at Home Complement or Replace Centre-based Therapeutic Feeding Programmes for Severe Malnutrition?

OpenAIRE

Gaboulaud, Valérie; Dan-Bouzoua, N; Brasher, C; Fedida, G; Gergonne, B; Brown, Vincent

2007-01-01

To measure the success rate of three different strategies used in Médecins Sans Frontières large-scale therapeutic nutritional rehabilitation programme in Niger, we analysed three cohorts of severely malnourished patients in terms of daily weight gain, length of stay, recovery, case fatality and defaulting. A total of 1937 children aged 6-59 months were followed prospectively from 15 August 2002 to 21 October 2003. For the three cohorts, 660 children were maintained in the therapeutic feeding...

Effectiveness of therapeutic barium enema for diverticular hemorrhage.

Science.gov (United States)

Matsuura, Mizue; Inamori, Masahiko; Nakajima, Atsushi; Komiya, Yasuhiko; Inoh, Yumi; Kawasima, Keigo; Naitoh, Mai; Fujita, Yuji; Eduka, Akiko; Kanazawa, Noriyoshi; Uchiyama, Shiori; Tani, Rie; Kawana, Kennichi; Ohtani, Setsuya; Nagase, Hajime

2015-05-14

To evaluate the effectiveness of barium impaction therapy for patients with colonic diverticular bleeding. We reviewed the clinical charts of patients in whom therapeutic barium enema was performed for the control of diverticular bleeding between August 2010 and March 2012 at Yokohama Rosai Hospital. Twenty patients were included in the review, consisting of 14 men and 6 women. The median age of the patients was 73.5 years. The duration of the follow-up period ranged from 1 to 19 mo (median: 9.8 mo). Among the 20 patients were 11 patients who required the procedure for re-bleeding during hospitalization, 6 patients who required it for re-bleeding that developed after the patient left the hospital, and 3 patients who required the procedure for the prevention of re-bleeding. Barium (concentration: 150 w%/v%) was administered per the rectum, and the leading edge of the contrast medium was followed up to the cecum by fluoroscopy. After confirmation that the ascending colon and cecum were filled with barium, the enema tube was withdrawn, and the patient's position was changed every 20 min for 3 h. Twelve patients remained free of re-bleeding during the follow-up period (range: 1-19 mo) after the therapeutic barium enema, including 9 men and 3 women with a median age of 72.0 years. Re-bleeding occurred in 8 patients including 5 men and 3 women with a median age of 68.5 years: 4 developed early re-bleeding, defined as re-bleeding that occurs within one week after the procedure, and the remaining 4 developed late re-bleeding. The DFI (disease-free interval) decreased 0.4 for 12 mo. Only one patient developed a complication from therapeutic barium enema (colonic perforation). Therapeutic barium enema is effective for the control of diverticular hemorrhage in cases where the active bleeding site cannot be identified by colonoscopy.

Chronically ill patients’ expectations of therapeutic education and their health locus of control

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Małgorzata Anna Basińska

2015-12-01

Full Text Available Background Beliefs as cognitive components of personality indicate what we consider as true or false and help us to answer questions concerning others, the world surrounding us and situations that we encounter. Beliefs about the health locus of control and their relations with expectations pertaining to therapeutic education seem to be of vital importance in the case of occurrence of a chronic illness. The aim of this paper is to verify whether expectations concerning therapeutic education in chronically ill patients demonstrate a relation with beliefs about the health locus of control and whether they vary according to gender, age and health, and to present the results of research that applies the Polish OE-15 scale for the evaluation of therapeutic education expectations depending on the health condition. Participants and procedure Two hundred and ninety-one persons were examined, including 180 patients and 111 healthy controls (the control group, 187 women and 104 men. The average age of subjects was 45.71 (SD = 13.51 years, ranging from 21 to 80 years. The OE-15 Therapeutic Education Expectations Scale and the Multidimensional Health Locus of Control Scale in versions relevant for patients and healthy controls as well as demographics were used. Results Age, gender and beliefs about the health locus of control are related to expectations of therapeutic education. Conclusions When providing therapeutic education for chronically ill patients, one should assess their expectations and pay attention to patients’ beliefs about the health locus of control.

New Insights into the Pathogenesis of MDS and the rational therapeutic opportunities.

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Abou Zahr, Abdallah; Bernabe Ramirez, Carolina; Wozney, Jocelyn; Prebet, Thomas; Zeidan, Amer M

2016-01-01

Myelodysplastic syndromes (MDS) include a heterogeneous group of acquired hematopoietic malignancies characterized by ineffective hematopoiesis, peripheral cytopenias, and a varying propensity for progression to acute myeloid leukemia. The clinical heterogeneity in MDS is a reflection of its molecular heterogeneity. Better understanding of aberrant epigenetics, dysregulation of immune responses, and del(5q) MDS has provided the rationale for well-established treatments in MDS. Further understanding of abnormal signal transduction and aberrant apoptosis pathways has led to development of new rational therapies that are in advanced phases of clinical translation. This review seeks to describe recent developments in our understanding of the pathogenesis of MDS and the potential therapeutic implications of these observations.

GNX-4728, a Novel Small Molecule Drug Inhibitor of Mitochondrial Permeability Transition, is Therapeutic in a Mouse Model of Amyotrophic Lateral Sclerosis

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Lee J Martin

2014-12-01

Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurological disorder in humans characterized by progressive degeneration of skeletal muscle and motor neurons in spinal cord, brainstem, and cerebral cortex causing skeletal muscle paralysis, respiratory insufficiency, and death. There are no cures or effective treatments for ALS. ALS can be inherited, but most cases are not associated with a family history of the disease. Mitochondria have been implicated in the pathogenesis but definitive proof of causal mechanisms is lacking. Identification of new clinically translatable disease mechanism-based molecular targets and small molecule drug candidates are needed for ALS patients. We tested the hypothesis in an animal model that drug modulation of the mitochondrial permeability transition pore (mPTP is therapeutic in ALS. A prospective randomized placebo-controlled drug trial was done in a transgenic mouse model of ALS. We explored GNX-4728 as a therapeutic drug. GNX-4728 inhibits mPTP opening as evidenced by increased mitochondrial calcium retention capacity both in vitro and in vivo. Chronic systemic treatment of G37R-human mutant superoxide dismutase-1 (hSOD1 transgenic mice with GNX-4728 resulted in major therapeutic benefits. GNX-4728 slowed disease progression and significantly improved motor function. The survival of ALS mice was increased significantly by GNX-4728 treatment as evidence by a nearly 2-fold extension of lifespan (360 days to 750 days. GNX-4728 protected against motor neuron degeneration and mitochondrial degeneration, attenuated spinal cord inflammation, and preserved neuromuscular junction innervation in the diaphragm in ALS mice. This work demonstrates that a mPTP-acting drug has major disease-modifying efficacy in a preclinical mouse model of ALS and establishes mitochondrial calcium retention, and indirectly the mPTP, as targets for ALS drug development.

[Thinking of therapeutic mechanism of small knife needle in treating closed myofascitis].

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Zhao, Yong; Fang, Wei; Qin, Wei-kai

2014-09-01

The authors investigated and discussed therapeutic mechanism of small knife needle in treating closed myofascitis on the basis of pathomechanism of modern medicine and acupuncture theory of TCM among numbers of clinical cases and experimental data. Therapeutic mechanism lies in 6 aspects: (1) Relieve the energy crisis of tenderness point on muscular fasciae; (2) Affect nervous system and reduce induction of harmful stimulating signal; (3) Inhibit aseptic inflammatory reaction on muscular fasciae; (4) Regulate dynamic equilibrium of soft tissue by cutting scar and releasing the conglutination; (5) Increase patients' regional threshold of feeling; (6) Reduce tension and pressure of soft tissue of tenderness point so as to relieve extrusion of nervus cutaneous.

Septicemia in a Neonate following Therapeutic Hypothermia: The Literature Review of Evidence

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Kam Lun Hon

2013-01-01

Full Text Available We report a term neonate with hypoxic ischemic encephalopathy who underwent a 72-hour therapeutic hypothermia. He developed unstable body temperature associated with coagulase negative staphylococcus septicemia 2 weeks later which was promptly treated with intravenous antibiotics and made a good recovery. PubMed (a service of the U.S. National Library of Medicine was searched for the terms “therapeutic hypothermia” and “septicemia,” with limits activated (humans, English, age 0–18 years. There were only 6 randomized controlled trials, 1 non-randomized controlled trial, 1 retrospective cohort, and 1 case-control trial, which showed no definite evidence of increased risk of septicemia or neutrophil dysfunction in infants following hypothermia therapy.

Implications of publicly available genomic data resources in searching for therapeutic targets of obesity and type 2 diabetes.

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Jung, Sungwon

2018-04-20

Obesity and type 2 diabetes (T2D) are two major conditions that are related to metabolic disorders and affect a large population. Although there have been significant efforts to identify their therapeutic targets, few benefits have come from comprehensive molecular profiling. This limited availability of comprehensive molecular profiling of obesity and T2D may be due to multiple challenges, as these conditions involve multiple organs and collecting tissue samples from subjects is more difficult in obesity and T2D than in other diseases, where surgical treatments are popular choices. While there is no repository of comprehensive molecular profiling data for obesity and T2D, multiple existing data resources can be utilized to cover various aspects of these conditions. This review presents studies with available genomic data resources for obesity and T2D and discusses genome-wide association studies (GWAS), a knockout (KO)-based phenotyping study, and gene expression profiles. These studies, based on their assessed coverage and characteristics, can provide insights into how such data can be utilized to identify therapeutic targets for obesity and T2D.

Interpretation of metabolic acidosis in critically ill patients according to the Stewart theory, ICU Case report

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Adolfo León Tróchez

2010-03-01

Full Text Available The present case is about a 79 years old patient with a history of hypertension, cerebral stroke and untreated inguinal hernia diagnosed 30 years ago, who underwent an emergent umbilical and right crural herniorrhaphy, the surgical procedure was complicated by a regurgitation and aspiration of gastric content. Postoperatively the patient suffered from progressive shortness of breath, requiring ICU admission. She soon developed septic shock of pulmonary origin and with severe decompensated metabolic acidosis associated with lactic acidosis. The patient died after a short time in intensive care. We propose to analyse and illustrate the acid-base aspects of the case according to the Stewart approach, exposing the factors that determine the acid-base factors and their therapeutic implications.

Structural insights into the molecular mechanisms of myasthenia gravis and their therapeutic implications

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Noridomi, Kaori; Watanabe, Go; Hansen, Melissa N.; Han, Gye Won; Chen, Lin (USC)

2017-04-25

The nicotinic acetylcholine receptor (nAChR) is a major target of autoantibodies in myasthenia gravis (MG), an autoimmune disease that causes neuromuscular transmission dysfunction. Despite decades of research, the molecular mechanisms underlying MG have not been fully elucidated. Here, we present the crystal structure of the nAChR α1 subunit bound by the Fab fragment of mAb35, a reference monoclonal antibody that causes experimental MG and competes with ~65% of antibodies from MG patients. Our structures reveal for the first time the detailed molecular interactions between MG antibodies and a core region on nAChR α1. These structures suggest a major nAChR-binding mechanism shared by a large number of MG antibodies and the possibility to treat MG by blocking this binding mechanism. Structure-based modeling also provides insights into antibody-mediated nAChR cross-linking known to cause receptor degradation. Our studies establish a structural basis for further mechanistic studies and therapeutic development of MG.

[Localized scleroderma: a retrospective study about 92 cases].

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El Fékih, Nadia; Réjaibi, Iménc; Kamoun, Hajer; Zéglaoui, Faten; Fazaa, Bécima; Kharfi, Monia; Kamoun, Mohamed Ridha

2009-09-01

Sclerodermas are rare affections which can be located or generalized. Localized form is the most frequent. The purpose of this study was to describe epidemiologic, clinics, biological, immunological, therapeutic, evolutionary characteristics of the localized scleroderma through a personal series and the data of the literature. We have performed a retrospective study on all patients followed in the department of dermatology of the Hospital Charles Nicole during 14 years period. Our study was about 92 cases of localized scleroderma (73 were females and 19 males). The mean age was 35 years (between 2 and 72 years). The majority of localised sclerodermas (66.2% of the cases) appeared before 40 years with a maximum of frequency between 10 and 30 years (41.6%). Only 11.9% of the cases were observed before 10 years. They were 51 cases (55%) of morphea, 35 cases (38%) of scleroderma in bands including 32 linear scleroderma and 3 scleroderma en coup de sabre, 5 cases (5.5%) of generalized morphea and 1 case (0.15%) of deep morphea. Average therapeutic was specified among 63 patients (87%), and the evolution could be appreciated among 45 patients. The epidemiologic data observed in our series are comparable with those reported in the literature. Therapeutic difficulties and risks of functional after-effects, particular in scleroderma in bands, remain the principal concern for all the authors.

Acute nutritional ketosis: implications for exercise performance and metabolism

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2014-01-01

Ketone bodies acetoacetate (AcAc) and D-β-hydroxybutyrate (βHB) may provide an alternative carbon source to fuel exercise when delivered acutely in nutritional form. The metabolic actions of ketone bodies are based on sound evolutionary principles to prolong survival during caloric deprivation. By harnessing the potential of these metabolic actions during exercise, athletic performance could be influenced, providing a useful model for the application of ketosis in therapeutic conditions. This article examines the energetic implications of ketone body utilisation with particular reference to exercise metabolism and substrate energetics. PMID:25379174

Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications.

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Logan, Randall; Funk, Ryan S; Axcell, Erick; Krise, Jeffrey P

2012-08-01

Many commercially available, weakly basic drugs have been shown to be lysosomotropic, meaning they are subject to extensive sequestration in lysosomes through an ion trapping-type mechanism. The extent of lysosomal trapping of a drug is an important therapeutic consideration because it can influence both activity and pharmacokinetic disposition. The administration of certain drugs can alter lysosomes such that their accumulation capacity for co-administered and/or secondarily administered drugs is altered. In this review the authors explore what is known regarding the mechanistic basis for drug-drug interactions involving lysosomes. Specifically, the authors address the influence of drugs on lysosomal pH, volume and lipid processing. Many drugs are known to extensively accumulate in lysosomes and significantly alter their structure and function; however, the therapeutic and toxicological implications of this remain controversial. The authors propose that drug-drug interactions involving lysosomes represent an important potential source of variability in drug activity and pharmacokinetics. Most evaluations of drug-drug interactions involving lysosomes have been performed in cultured cells and isolated tissues. More comprehensive in vivo evaluations are needed to fully explore the impact of this drug-drug interaction pathway on therapeutic outcomes.

In Silico Characterization of Hras Pathway for Therapeutic Implications Against Cancer

International Nuclear Information System (INIS)

Amjad, S.; Naz, A.; Malik, M. F. A.

2015-01-01

Hras (v-Ha-ras Harvey rat sarcoma viral oncogene homolog) plays a pivotal role in breast tumorigenesis. Expressional aberrations in Hras has significantly been correlated with patient's poor overall survival. In the present study, in silico characterization of Hras to trigger downstream effectors including raf, mek, erk has been explored. Three mutational hotspots for Hras (condons12, 13, 61) have been retrieved from the literature. Promoter modelling using Proscan software revealed a promoter region lacking TATA sequence. To study the epigenetic modifications, methylation analysis of promoter lacking TATA box was done using Methylator software. Methylation is directly correlated with tumor targeting therapies as it represses expression of certain oncogenes. Five candidate sites for hypermethylation of Hras were predicted. Analysis of protein residues involved in interlocking with its downstream effector proteins was also uncovered. In addition to this, a diagnostic and therapeutic relevance of micro RNAs (miRNAs/miRs) specifically acting either as oncogene or tumor suppressors on Hras mediated pathway have been identified. Seven micro RNAs (Let-7, miR-195, miR-497, miR-184, miR-34a, miR-34c, miR-155) found to be responsible for down regulating expression of proteins involved in ressignalling cascade while miR-372 and miR373, miR-212, miR206/21 and miR-17-92 cluster are known to elevate rassignalling pathway. Interestingly, dysregulated expression of Let-7, miR-195, miR-497, miR-184, miR-34, miR-155 co-related with poor prognosis in different cancers has also supported these in silico findings. (author)

Etiological and therapeutical observations in a case of belly dancer's dyskinesia.

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Linazasoro, Girutz; Van Blercom, Nadège; Lasa, Asier; Fernández, José Manuel; Aranzábal, Inés

2005-02-01

We report on the case of a woman with belly dancer's syndrome. This case presented two peculiarities: (1) the condition was induced by the chronic use of clebopride, and (2) abdominal dyskinesias showed a dramatic response to the application of transcutaneous electrical nerve stimulation. Copyright 2004 Movement Disorder Society.

Use of therapeutic surfactant lavage in a preterm infant with massive pulmonary hemorrhage

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Ino Kanavaki

2012-08-01

Full Text Available We report a case of a premature infant presenting with recurrent pulmonary hemorrhage in which we performed a therapeutic lavage with diluted surfactant after an acute episode of bleeding with severe intractable hypoxemia. Repeated small aliquots of diluted surfactant (10x2 mL allowed rapid improvement in oxygenation and reduction of required mean airway pressures during high frequency oscillatory ventilation. This observation may suggest that surfactant lavage could be beneficial in massive pulmonary hemorrhage in infants. A randomized controlled trial might be needed to clarify the potential benefit of this therapeutic intervention on outcome of infants suffering from this life-threatening complication.

The microbiota in inflammatory bowel disease: current and therapeutic insights

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Lane ER

2017-06-01

Full Text Available Erin R Lane,1 Timothy L Zisman,2 David L Suskind1 1Division of Gastroenterology and Hepatology, Seattle Children’s Hospital, 2Division of Gastroenterology, University of Washington, Seattle, WA, USA Abstract: Inflammatory bowel disease is a heterogeneous group of chronic disorders that result from the interaction of the intestinal immune system with the gut microbiome. Until recently, most investigative efforts and therapeutic breakthroughs were centered on understanding and manipulating the altered mucosal immune response that characterizes these diseases. However, more recent studies have highlighted the important role of environmental factors, and in particular the microbiota, in disease onset and disease exacerbation. Advances in genomic sequencing technology and bioinformatics have facilitated an explosion of investigative inquiries into the composition and function of the intestinal microbiome in health and disease and have advanced our understanding of the interplay between the gut microbiota and the host immune system. The gut microbiome is dynamic and changes with age and in response to diet, antibiotics and other environmental factors, and these alterations in the microbiome contribute to disease onset and exacerbation. Strategies to manipulate the microbiome through diet, probiotics, antibiotics or fecal microbiota transplantation may potentially be used therapeutically to influence modulate disease activity. This review will characterize the factors involved in the development of the intestinal microbiome and will describe the typical alterations in the microbiota that are characteristic of inflammatory bowel disease. Additionally, this manuscript will summarize the early but promising literature on the role of the gut microbiota in the pathogenesis of inflammatory bowel disease with implications for utilizing this data for diagnostic or therapeutic application in the clinical management of patients with these diseases. Keywords

The Impeding Role of Self-Critical Perfectionism on Therapeutic Alliance During Treatment and Eating Disorder Symptoms at Follow-up in Patients with an Eating Disorder

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Jolene van der Kaap-Deeder

2016-04-01

Full Text Available This study examines the impeding role of self-critical perfectionism at onset of treatment on therapeutic alliance during treatment and eating disorder symptoms at follow-up in patients with an eating disorder. Participants were 53 female patients with a mean age of 21.1 years treated for an eating disorder in a specialized inpatient treatment unit. Self-critical perfectionism was assessed at admission, therapeutic alliance was assessed during treatment (after three months of treatment, and eating disorder symptoms were assessed at admission, after three months and one year later. Self-critical perfectionism negatively related to treatment alliance with the therapist. Although self-critical perfectionism was not directly predictive of subsequent changes in eating disorder symptoms, it was indirectly related to less reduction in body dissatisfaction through the therapeutic alliance. These results point to the importance of self-critical perfectionism in the therapeutic alliance and in changes in body image problems. Treatment implications are discussed.

OBSERVATION ON THE THERAPEUTIC EFFECT OF TREATMENT OF 150CASES OF INSOMNIA BY PUNCTURING BODY ACUPOINTS AND OTOPOINTS

Institute of Scientific and Technical Information of China (English)

李宗莲

2000-01-01

In the present paper,the therapeutic effect of needling Baihui(GV20)and Sishen-chong(EX-HN1)combined with otopoint Xin(MA-IC),Shenmen,Naodian and pizhixia(MA-AT1)for treatment of insomnia was observed in 150patients.Results showed that the cure rate,effective rate and ineffective rate were84%,13.33%and2.67%respectively.Comparison between Western medicine group and acupuncture group showed a significant difference in the therapeutic effect(P<0.01).It displays that acupuncture can correct the imbalance between excitement and suppression of the cerebral cortex and had effects of tranquilizing and allaying excitement.

Use of anteromedial thigh perforator flap and immunological implications of Gorlin-Goltz syndrome: a case study.

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Scalise, A; Calamita, R; Tartaglione, C; Bolletta, E; Di Benedetto, G; Pierangeli, M

2016-12-02

Gorlin-Goltz syndrome is mainly characterised by the development of numerous multicentric and relapsing cutaneous basal cell carcinomas (BCCs). A major problem for patients with Gorlin-Goltz syndrome is the large amount of BCCs that can invade the deep underlying structures, especially the face. Here, we describe the case of a 23-year-old male affected by Gorlin-Goltz syndrome. He had recurrent BCCs on a hairless scalp and dorsum since he was 17 years old and underwent four surgical procedures to excise BCCs, including a reconstruction with anteromedial thigh perforator flap. For each of the surgical procedures, a phenotypic study on peripheral blood mononuclear cells using flow cytometry was performed on the same day of surgery, and on days 7, 14 and 21 after surgery. The role of the tumour-specific cytolytic immune response as a potential future treatment of syndromic BCCs and its trend in relation to surgical ablation of large portions of tumour tissue was examined, and the cosmetic and therapeutic results are shown.

Achieving the Promise of Therapeutic Extracellular Vesicles: The Devil is in Details of Therapeutic Loading.

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Sutaria, Dhruvitkumar S; Badawi, Mohamed; Phelps, Mitch A; Schmittgen, Thomas D

2017-05-01

Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for therapeutics owing to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity profiles. EVs can also be engineered to display targeting moieties on their surfaces which enables targeting to desired tissues, organs or cells. While much has been learned on the role of EVs as cell communicators, the field of therapeutic EV application is currently under development. Critical to the future success of EV delivery system is the description of methods by which therapeutics can be successfully and efficiently loaded within the EVs. Two methods of loading of EVs with therapeutic cargo exist, endogenous and exogenous loading. We have therefore focused this review on describing the various published approaches for loading EVs with therapeutics.

Utilization of diagnostic ultrasound and intravenous lipid-encapsulated perfluorocarbons in non-invasive targeted cardiovascular therapeutics.

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Porter, Thomas R; Choudhury, Songita A; Xie, Feng

2016-01-01

Diagnostic ultrasound (DUS) pressures have the ability to induce inertial cavitation (IC) of systemically administered microbubbles; this bioeffect has many diagnostic and therapeutic implications in cardiovascular care. Diagnostically, commercially available lipid-encapsulated perfluorocarbons (LEP) can be utilized to improve endocardial and vascular border delineation as well as assess myocardial perfusion. Therapeutically, the liquid jets induced by IC can alter endothelial function and dissolve thrombi within the immediate vicinity of the cavitating microbubbles. The cavitating LEP can also result in the localized release of any bound therapeutic substance at the site of insonation. DUS-induced IC has been tested in pre-clinical studies to determine what effect it has on acute vascular and microvascular thrombosis as well as nitric oxide (NO) release. These pre-clinical studies have consistently shown that DUS-induced IC of LEP is effective in restoring coronary vascular and microvascular flow in acute ST segment elevation myocardial infarction (STEMI), with microvascular flow improving even if upstream large vessel flow has not been achieved. The initial clinical trials examining the efficacy of short pulse duration DUS high mechanical index impulses in patients with STEMI are underway, and preliminary studies have suggested that earlier epicardial vessel recanalization can be achieved prior to arriving in the cardiac catheterization laboratory. DUS high mechanical index impulses have also been effective in pre-clinical studies for targeting DNA delivery that has restored islet cell function in type I diabetes and restored vascular flow in the extremities downstream from a peripheral vascular occlusion. Improvements in this technique will come from three dimensional arrays for therapeutic applications, more automated delivery techniques that can be applied in the field, and use of submicron-sized acoustically activated LEP droplets that may better permeate the

Phenotype/genotype correlations in Gaucher disease type 1: Clinical and therapeutic implications

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Sibille, A.; Eng, C.M.; Kim, S.J.; Pastores, G. (Mount Sinai School of Medicine, New York, NY (United States)); Grabowski, G.A. (Mount Sinai School of Medicine, New York, NY (United States) Univ. of Cincinnati, OH (United States))

1993-06-01

Gaucher disease is the most frequent lysosomal storage disease and the most prevalent genetic disease among Ashkenazi Jews. Gaucher disease type 1 is characterized by marked variability of the phenotype and by the absence of neuronopathic involvement. To test the hypothesis that this phenotypic variability was due to genetic compounds of several different mutant alleles, 161 symptomatic patients with Gaucher disease type 1 (> 90% Ashkenazi Jewish) were analyzed for clinical involvement, and their genotypes were determined. Qualitative and quantitative measures of disease involvement included age at onset of the disease manifestations, hepatic and splenic volumes, age at splenectomy, and severity of bony disease. High statistically significant differences (P < .005) were found in each clinical parameter in patients with the N370S/N370S genotype compared with those patients with the N370S/84GG, N370S/L444P, and N370/ genotypes. The symptomatic N370S homozygotes had onset of their disease two to three decades later than patients with the other genotypes. In addition, patients with the latter genotypes have much more severely involved livers, spleens, and bones and had a higher incidence of splenectomy at an earlier age. These predictive genotype analyses provide the basis for genetic care delivery and therapeutic recommendations in patients affected with Gaucher disease type 1. 38 refs., 1 fig., 4 tabs.

Therapeutic follow-up in hospitalization: social inclusion, recovery of citizenship and respect for individuality

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Regina Célia Fiorati

2008-01-01

Full Text Available This study was carried out in a psychiatric crisis hospitalization unit, with the aim of drawing up a proposal for implementing therapeutic follow-up as part of the therapeutic program at this unit. The concept of therapeutic follow-up was envisaged as an important resource to be included in psychosocial rehabilitation projects, with the following goals: linking users with extra-hospital services, avoiding re-hospitalization and achieving inclusion in social networks. The study consisted of an exploratory-descriptive case study with a qualitative approach to data. Participant observation and a field diary were the techniques used for gathering and recording data. The difficulties experienced were correlated with the spheres of social networks, family, institutional relationships and society. The results included heeding the patient's and the family's suffering and including users in social networks, extra-hospital services and community organizations.

Renal candidiasis in newborn: the ultrasonography as diagnostic and therapeutic method

International Nuclear Information System (INIS)

Lopez Pino, M.A.; Serrano Hernandez, C.; Alba Romero, C.; Aransay Bramtot, A.; Paul Diaz, L.

1995-01-01

We present a case of systemic candidiasis in a low-weight newborn. Renal involvement presented as unilateral hydronephrosis secondary to the fungal construction. Ultrasound served not only as a diagnostic tool, but as a guide for the performance of performance of percutaneous nephrostomy which was included in the therapeutic approach to decompress the excretory pathway and allow local installation of anti fungal agents. (Author) 16 refs

Therapeutics targeting tumor immune escape: towards the development of new generation anticancer vaccines.

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Mocellin, Simone; Nitti, Donato

2008-05-01

Despite the evidence that immune effectors can play a significant role in controlling tumor growth under natural conditions or in response to therapeutic manipulation, it is clear that malignant cells evade immune surveillance in most cases. Considering that anticancer vaccination has reached a plateau of results and currently no vaccination regimen is indicated as a standard anticancer therapy, the dissection of the molecular events underlying tumor immune escape is the necessary condition to make anticancer vaccines a therapeutic weapon effective enough to be implemented in the routine clinical setting. Recent years have witnessed significant advances in our understanding of the molecular mechanisms underlying tumor immune escape. These mechanistic insights are fostering the development of rationally designed therapeutics aimed at reverting the immunosuppressive circuits that undermine an effective antitumor immune response. In this review, the best characterized mechanisms that allow cancer cells to evade immune surveillance are overviewed and the most debated controversies constellating this complex field are highlighted. In addition, the latest therapeutic strategies devised to overcome tumor immune escape are described, with special regard to those entering clinical phase investigation. Copyright (c) 2007 Wiley-Periodicals, Inc.

Targeting reactive nitrogen species: a promising therapeutic strategy for cerebral ischemia-reperfusion injury.

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Chen, Xing-miao; Chen, Han-sen; Xu, Ming-jing; Shen, Jian-gang

2013-01-01

Ischemic stroke accounts for nearly 80% of stroke cases. Recanalization with thrombolysis is a currently crucial therapeutic strategy for re-building blood supply, but the thrombolytic therapy often companies with cerebral ischemia-reperfusion injury, which are mediated by free radicals. As an important component of free radicals, reactive nitrogen species (RNS), including nitric oxide (NO) and peroxynitrite (ONOO(-)), play important roles in the process of cerebral ischemia-reperfusion injury. Ischemia-reperfusion results in the production of nitric oxide (NO) and peroxynitrite (ONOO(-)) in ischemic brain, which trigger numerous molecular cascades and lead to disruption of the blood brain barrier and exacerbate brain damage. There are few therapeutic strategies available for saving ischemic brains and preventing the subsequent brain damage. Recent evidence suggests that RNS could be a therapeutic target for the treatment of cerebral ischemia-reperfusion injury. Herein, we reviewed the recent progress regarding the roles of RNS in the process of cerebral ischemic-reperfusion injury and discussed the potentials of drug development that target NO and ONOO(-) to treat ischemic stroke. We conclude that modulation for RNS level could be an important therapeutic strategy for preventing cerebral ischemia-reperfusion injury.

Economic and occupational implications of upstream activity. The Eni-Agip case

International Nuclear Information System (INIS)

Fazio, A.

2000-01-01

This report evaluates the national and regional economic implications, for Italy, of the exploration and development activity in the petroleum sector (at the domestic and international level), with reference being made to the specific case of Eni's Agip Division. The business considered here is basically of an investment nature; as a result, the supply of goods and services Agip Division requires of the Italian production sectors represents an autonomous component of the domestic demand, to which induced effects are attributable. The study has revealed that Eni-Agip's demand plays a central role in promoting domestic production and in the extent of the induced effects in terms of creation of added value and employment. From this point of view, the specific nature of its demand places Eni-Agip at the top of the system of the large domestic enterprises, whose role as the dynamo of the national economy has gradually decreased. Viceversa, Eni-Agip's ability to promote domestic production and employment proves to be lower than that of the sectors where the presence of medium- and small- sized firms is prevalent, a fact that confirms their increasing role in the Italian economy. As far the territorial aspect is concerned, the promotion of production and jobs brought about by Eni-Agip's demand obviously affects the country's most productive regions, especially where industrial supplies are involved, but its specific regional distribution entails also a significant local interest in different central-southern regions of the country [it

True recurrence vs. new primary ipsilateral breast tumor relapse: An analysis of clinical and pathologic differences and their implications in natural history, prognoses, and therapeutic management

International Nuclear Information System (INIS)

Smith, Tanya E.; Lee, Daesung; Turner, Bruce C.; Carter, Darryl; Haffty, Bruce G.

2000-01-01

Purpose: The purpose of this study was to classify all ipsilateral breast tumor relapses (IBTR) in patients treated with conservative surgery and radiation therapy (CS+RT) as either new primary tumors (NP) or true local recurrences (TR) and to assess the prognostic and therapeutic implications of this classification. Methods and Materials: Of the 1152 patients who have been treated at Yale-New Haven Hospital before 1990, 136 patients have experienced IBTR as their primary site of failure. These relapses were classified as either NP or TR. Specifically, patients were classified as NP if the recurrence was distinctly different from the primary tumor with respect to the histologic subtype, the recurrence location was in a different location, or if the flow cytometry changed from aneuploid to diploid. This information was determined by a detailed review of each patient's hospital and/or radiotherapy record, mammograms, and pathologic reports. Results: As of 2/99, with a mean follow-up of 14.2 years, the overall ipsilateral breast relapse-free rate for all 1152 patients was 86% at 10 years. Using the classification scheme outlined above, 60 patient relapses were classified as TR, 70 were classified as NP and 6 were unable to be classified. NP patients had a longer mean time to breast relapse than TR patients (7.3 years vs. 3.7 years, p < 0.0001) and were significantly younger than TR patients (48.9 years vs. 54.5 years, p < 0.01). Patients developed both TR and NP at similar rates until approximately 8 years, when TR rates stabilized but NP rates continued to rise. By 15 years following original diagnosis, the TR rate was 6.8% compared to 13.1% for NP. Of the patients who had been previously tested for BRCA1/2 mutations, 17% (8/52) had deleterious mutations. It is noteworthy that all patients with deleterious mutations had new primary IBTR, while patients without deleterious mutations had both TR and NP (p = 0.06). Ploidy was evenly distributed between TR and NP but NP

Reactor-produced therapeutic radioisotopes

International Nuclear Information System (INIS)

Knapp, F.F. Jr.

2002-01-01

The significant worldwide increase in therapeutic radioisotope applications in nuclear medicine, oncology and interventional cardiology requires the dependable production of sufficient levels of radioisotopes for these applications (Reba, 2000; J. Nucl. Med., 1998; Nuclear News, 1999; Adelstein and Manning, 1994). The issues associated with both accelerator- and reactor-production of therapeutic radioisotopes is important. Clinical applications of therapeutic radioisotopes include the use of both sealed sources and unsealed radiopharmaceutical sources. Targeted radiopharmaceutical agents include those for cancer therapy and palliation of bone pain from metastatic disease, ablation of bone marrow prior to stem cell transplantation, treatment modalities for mono and oligo- and polyarthritis, for cancer therapy (including brachytherapy) and for the inhibition of the hyperplastic response following coronary angioplasty and other interventional procedures (For example, see Volkert and Hoffman, 1999). Sealed sources involve the use of radiolabeled devices for cancer therapy (brachytherapy) and also for the inhibition of the hyperplasia which is often encountered after angioplasty, especially with the exponential increase in the use of coronary stents and stents for the peripheral vasculature and other anatomical applications. Since neutron-rich radioisotopes often decay by beta decay or decay to beta-emitting daughter radioisotopes which serve as the basis for radionuclide generator systems, reactors are expected to play an increasingly important role for the production of a large variety of therapeutic radioisotopes required for these and other developing therapeutic applications. Because of the importance of the availability of reactor-produced radioisotopes for these applications, an understanding of the contribution of neutron spectra for radioisotope production and determination of those cross sections which have not yet been established is important. This

DNA interstrand cross-link repair: understanding role of Fanconi anemia pathway and therapeutic implications.

Science.gov (United States)

Shukla, Pallavi; Solanki, Avani; Ghosh, Kanjaksha; Vundinti, Babu Rao

2013-11-01

Interstrand cross-links (ICLs) are extremely toxic DNA lesions that prevent DNA double-helix separation due to the irreversible covalent linkage binding of some agents on DNA strands. Agents that induce these ICLs are thus widely used as chemotherapeutic drugs but may also lead to tumor growth. Fanconi anemia (FA) is a rare genetic disorder that leads to ICL sensitivity. This review provides update on current understanding of the role of FA proteins in repairing ICLs at various stages of cell cycle. We also discuss link between DNA cross-link genotoxicity caused by aldehydes in FA pathway. Besides this, we summarize various ICL agents that act as drugs to treat different types of tumors and highlight strategies for modulating ICL sensitivity for therapeutic interventions that may be helpful in controlling cancer and life-threatening disease, FA. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Corporal punishment contestations, paradoxes and implications for ...

African Journals Online (AJOL)

Corporal punishment contestations, paradoxes and implications for school leadership: A case study of two South African high schools. ... South African Journal of Education. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current ...

EXETRA Perspectives: Concepts in Therapeutic Recreation.

Science.gov (United States)

Neal, Larry L.; Edginton, Christopher R.

Fifteen papers address issues in therapeutic recreation for disabled persons from the perspectives of practitioners, educators, and students. The following papers are presented. "Therapeutic Recreation Service: The Past and Challenging Present" (H. Sessoms); "Therapeutic Recreatiion in an Era of Limits: A Crisis...A Challenge... An Opportunity"…

[Acute appendicitis: clinico-diagnostic and therapeutic considerations].

Science.gov (United States)

Carditello, A; Bartolotta, M; Bonavita, G; Lentini, B; Sturniolo, G

1985-04-01

Since january 1970-december 1982, 58 patients underwent emergently appendectomy for acute appendicitis. 31 (53,4 percent) where males; the average age was 21 +/- 2,3 years (M +/- SEM). The duration of symptoms ranged from 1-6 hours (10,3 percent of cases) to over 48 hours, before the hospital admission (15,4 percent of cases). 27 patients (46,5 percent) had a clinical examination at home by a physician. 21 patients (36,4 percent) came to hospital emergency unit without previous physical examination; 10 (17,2 percent) were transferred from other departments. In 6,9 percent of cases was present a perforated appendicitis with peritonitis. During operation, in 50 percent of patients was performed a therapeutic peritoneal lavage. In 63,7 percent of cases multiple drains were placed in peritoneal cavity. In all patients was effected postoperative antibiotic profilaxis. The mortality rate was 3,4 percent. General complications were observed more in patients with perforated appendicitis. This review suggests the following remarcable data: morbidity of this disease is still high; the physical examination is more important than laboratory work (especially in the elderly patients, which are often immunodepressed and in children, with leucocitosis-lack at hospital admission); early surgery is the most important factor to the improvement of prognosis in these cases and the results of surgical treatment are improved by large vertical incisions, peritoneal lavage and application of multiple intracavitary drains.

Use of perampanel in one case of super-refractory hypoxic myoclonic status: Case report

Directory of Open Access Journals (Sweden)

Estevo Santamarina

2015-01-01

Conclusion: This case shows the potential utility of PER as a therapeutic option in super-refractory hypoxic status and even its potential use before other aggressive alternatives considering their greater morbidity.

Therapeutic assessment with an adolescent: choosing connections over substances.

Science.gov (United States)

Austin, Cynthia A; Krumholz, Lauren S; Tharinger, Deborah J

2012-01-01

This case study provides an in-depth example of a comprehensive therapeutic assessment with an adolescent (TA-A) and his parents. The TA-A addressed parental concerns about their son's drug experimentation as well as the adolescent's own private questions about his distinctiveness from others, all set against a backdrop of ongoing parental conflict and poor communication. The TA-A process and how it is specifically tailored to balance the needs of adolescents and their parents is discussed. Subsequently, each step of TA-A is illustrated through the case study. Research findings at the conclusion of the assessment and at follow-up indicated significant decreases in internalizing symptomology and school problems, increases in self-esteem and self-reliance, and improved family functioning as reported by the adolescent. At follow-up, the father spoke of developing a more assertive parenting approach and successful follow-through on recommendations. This case study provides a template for clinicians interested in conducting TA-A.

Therapeutic implication of L-phenylalanine aggregation mechanism and its modulation by D-phenylalanine in phenylketonuria

Science.gov (United States)

Singh, Virender; Rai, Ratan Kumar; Arora, Ashish; Sinha, Neeraj; Thakur, Ashwani Kumar

2014-01-01

Self-assembly of phenylalanine is linked to amyloid formation toxicity in phenylketonuria disease. We are demonstrating that L-phenylalanine self-assembles to amyloid fibrils at varying experimental conditions and transforms to a gel state at saturated concentration. Biophysical methods including nuclear magnetic resonance, resistance by alpha-phenylglycine to fibril formation and preference of protected phenylalanine to self-assemble show that this behaviour of L-phenylalanine is governed mainly by hydrophobic interactions. Interestingly, D-phenylalanine arrests the fibre formation by L-phenylalanine and gives rise to flakes. These flakes do not propagate further and prevent fibre formation by L-phenylalanine. This suggests the use of D-phenylalanine as modulator of L-phenylalanine amyloid formation and may qualify as a therapeutic molecule in phenylketonuria. PMID:24464217

Restructuring patient flow logistics around patient care needs: implications and practicalities from three critical cases.

Science.gov (United States)

Villa, Stefano; Barbieri, Marta; Lega, Federico

2009-06-01

To make hospitals more patient-centered it is necessary to intervene on patient flow logistics. The study analyzes three innovative redesign projects implemented at three Italian hospitals. The three hospitals have reorganized patient flow logistics around patient care needs using, as proxies, the expected length of stay and the level of nursing assistance. In order to do this, they have extensively revised their logistical configuration changing: (1) the organization of wards, (2) the hospital's physical lay-out, (3) the capacity planning system, and (4) the organizational roles supporting the patient flow management. The study describes the changes implemented as well as the results achieved and draws some general lessons that provide useful hints for those other hospitals involved in such type of redesign projects. The paper ends by discussing some policy implications. In fact, the results achieved in the three cases investigated provide interesting material for further discussion on clinical, operational, and economic issues.

The pedagogical implications of information and communication ...

African Journals Online (AJOL)

The pedagogical implications of information and communication technology on adult education: a case study of the osun state colleges of ... Finally, the department should give individual students access to the use of 1C1 equipment.

ALK receptor activation, ligands and therapeutic targeting in glioblastoma and in other cancers

International Nuclear Information System (INIS)

Wellstein, Anton

2012-01-01

The intracellular anaplastic lymphoma kinase (ALK) fragment shows striking homology with members of the insulin receptor family and was initially identified as an oncogenic fusion protein resulting from a translocation in lymphoma and more recently in a range of cancers. The full-length ALK transmembrane receptor of ~220 kDa was identified based on this initial work. This tyrosine kinase receptor and its ligands, the growth factors pleiotrophin (PTN) and midkine (MK) are highly expressed during development of the nervous system and other organs. Each of these genes has been implicated in malignant progression of different tumor types and shown to alter phenotypes as well as signal transduction in cultured normal and tumor cells. Beyond its role in cancer, the ALK receptor pathway is thought to contribute to nervous system development, function, and repair, as well as metabolic homeostasis and the maintenance of tissue regeneration. ALK receptor activity in cancer can be up-regulated by amplification, overexpression, ligand binding, mutations in the intracellular domain of the receptor and by activity of the receptor tyrosine phosphatase PTPRz. Here we discuss the evidence for ligand control of ALK activity as well as the potential prognostic and therapeutic implications from gene expression and functional studies. An analysis of 18 published gene expression data sets from different cancers shows that overexpression of ALK, its smaller homolog LTK (leukocyte tyrosine kinase) and the ligands PTN and MK in cancer tissues from patients correlate significantly with worse course and outcome of the disease. This observation together with preclinical functional studies suggests that this pathway could be a valid therapeutic target for which complementary targeting strategies with small molecule kinase inhibitors as well as antibodies to ligands or the receptors may be used.

[Urological emergencies at the Dakar university teaching hospital: epidemiological, clinical and therapeutic features].

Science.gov (United States)

Fall, B; Diao, B; Fall, P A; Diallo, Y; Sow, Y; Ondongo, A A M; Diagana, M; Ndoye, A K; Ba, M; Diagne, B A

2008-11-01

To present the epidemiological, clinical and therapeutic features of the urological emergencies in Senegal, West Africa. The authors conducted a 20 months retrospective study that analyzed the epidemiological, clinical and therapeutic features of all urological emergencies admitted to the urology department of the university teaching hospital Aristide-Le-Dantec (Dakar). There were 1237 urological emergencies. The mean age of the patients was 58.8 years (range one month-94 years). The sex ratio (M/F) was 20.32. These patients had an age equal to or higher than 60 years in 50.7% of the cases. The most frequent illness was urinary retention (53%) and genitor-urinary system infectious, which represented as a whole 16.4% of the cases. The gangrenes of male external genitalia (Fournier's gangrene) accounted for 4.1% of the cases and the priapism 1.3%. In emergency, 331 surgical operations were performed. The most performed procedures were the installation of a suprapubic catheter (59.8%) and debridement of a gangrene of male external genitalia (15.4%). The most frequent urological emergency in our country was the acute urinary retention. Some serious illness like gangrene of male external genitalia (Fournier's gangrene) and priapism are not rare there.

FDG PET as a prognostic predictor in the early post-therapeutic evaluation for unresectable hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Higashi, Tatsuya; Nishii, Ryuichi [Shiga Medical Center Research Institute, Moriyama City, Shiga (Japan); Hatano, Etsuro; Ikai, Iwao; Seo, Satoru; Kitamura, Koji; Takada, Yasuji; Kamimoto, Shinji [Kyoto University Graduate School of Medicine, Department of Gastroenterological Surgery, Sakyo-ku, Kyoto (Japan); Nakamoto, Yuji; Ishizu, Koichi; Suga, Tsuyoshi; Kawashima, Hidekazu; Togashi, Kaori [Kyoto University Graduate School of Medicine, Department of Diagnostic Imaging and Nuclear Medicine, Sakyo-ku, Kyoto (Japan)

2010-03-15

To elucidate the prognostic role of post-therapeutic {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET), we conducted a retrospective cohort study analysing the clinical factors that affect overall survival after non-operative therapy for unresectable hepatocellular carcinoma (HCC). Sixty-seven cases with unresectable HCC who received non-operative therapy (transcatheter arterial chemoembolization: n=24, transcatheter arterial infusion chemotherapy: n=31, radiofrequency ablation: n = 5 or systemic chemotherapy: n = 7) and had received FDG PET for the evaluation of the therapeutic effect within 1 month after the end of the therapy were evaluated. Overall survival rate was evaluated using the univariate and multivariate analyses of relevant clinical and laboratory parameters before and after therapy, including visual PET analysis and quantitative analysis using maximum standardized uptake value (SUV). Visual PET diagnosis of post-therapeutic lesions was a good predictor of overall survival of unresectable HCC patients. The low FDG group showed significantly longer survival (average: 608 days) than that (average: 328 days) of the high FDG group (p<0.0001). Multivariate analysis showed four significant prognostic factors for the survival: post-therapeutic alpha-fetoprotein ({alpha}FP) level (=400 ng/ml, p=0.004), post-therapeutic visual PET diagnosis (p=0.006), post-therapeutic clinical stage (UICC stage IV, p=0.04) and post-therapeutic Milan criteria (p=0.03), while pre-therapeutic clinical factors, SUV by post-therapeutic FDG PET (5.0 or more) or others did not show significance. The present study suggests that post-therapeutic PET performed within 1 month after non-operative therapy can be a good predictor of overall survival in unresectable HCC patients, while pre-therapeutic evaluation including PET, tumour markers and clinical staging may not be useful. (orig.)

PARP-1 and PARP-2 activity in cancer-induced cachexia: potential therapeutic implications.

Science.gov (United States)

Barreiro, Esther; Gea, Joaquim

2018-01-26

Skeletal muscle dysfunction and mass loss is a characteristic feature in patients with chronic diseases including cancer and acute conditions such as critical illness. Maintenance of an adequate muscle mass is crucial for the patients' prognosis irrespective of the underlying condition. Moreover, aging-related sarcopenia may further aggravate the muscle wasting process associated with chronic diseases and cancer. Poly(adenosine diphosphate-ribose) polymerase (PARP) activation has been demonstrated to contribute to the pathophysiology of muscle mass loss and dysfunction in animal models of cancer-induced cachexia. Genetic inhibition of PARP activity attenuated the deleterious effects seen on depleted muscles in mouse models of oncologic cachexia. In the present minireview the mechanisms whereby PARP activity inhibition may improve muscle mass and performance in models of cancer-induced cachexia are discussed. Specifically, the beneficial effects of inhibition of PARP activity on attenuation of increased oxidative stress, protein catabolism, poor muscle anabolism and mitochondrial content and epigenetic modulation of muscle phenotype are reviewed in this article. Finally, the potential therapeutic strategies of pharmacological PARP activity inhibition for the treatment of cancer-induced cachexia are also being described in this review.

[Predictors of the therapeutic discharge in patients with dual pathology admitted to a therapeutic community with a psychiatric unit].

Science.gov (United States)

Madoz-Gúrpide, Agustín; García Vicent, Vicente; Luque Fuentes, Encarnación; Ochoa Mangado, Enriqueta

2013-01-01

This study aims to analyze the variables on which depends therapeutic discharge, in patients with a severe dual diagnosis admitted to a professional therapeutic community where their pathology is treated. 325 patients admitted between June 2000 and June 2009 to the therapeutic community. This is a retrospective, cross-sectional study with no control group, based on the detailed analysis of the information collected in a model of semi-structured clinical interview designed in the therapeutic community. The 29.5% of the individuals included in the sample were therapeutically discharged. Of all the variables introduced in this analysis the most significant ones were gender, age at the beginning of treatment, education level, opiate dependence, polidrug abuse, and the presence of psychotic disorders and borderline personality disorder. In our study, gender determines the type of discharge, being therapeutic discharge more frequent among women. A higher educational also increases a better prognosis with a higher rate of therapeutic discharge among individuals with higher education level. A later age at the beginning of the treatment reduces the likelihood of therapeutic discharge. Likewise, polidrug abuse, diagnosis of psychotic disorders and borderline personality disorder are associated to a lower rate of therapeutic discharge. Recognizing these characteristics will allow the early identification of those patients more at risk of dropping treatment hastily, while trying to prevent it by increasing the therapeutic intensity.

[Therapeutic approaches to improve blood glucose control in a patient with type 2 diabetes on a metformin-sulfonylurea combination].

Science.gov (United States)

Scheen, A J; Paquot, N

2011-04-01

Beyond lifestyle changes, the management of type 2 diabetes comprises the administration of oral glucose-lowering agents, especially the classical metformin-sulfonylurea combination. If such a dual oral therapy could not (any more) obtain an adequate glucose control, intensified management becomes mandatory. Several therapeutic approaches may be proposed at this stage, with some advantages and disadvantages of each of them. The present clinical case aims at illustrating such difficult therapeutic choice. We will provide the pro-contra arguments concerning each therapeutic alternative and describe the practical modalities of an appropriate management according to the patient's characteristics.

Gradient dissimilation in Mongolian: Implications for diachrony

DEFF Research Database (Denmark)

Jatteau, Adèle; Hejná, Michaela

2018-01-01

This paper explores the implications of ‘gradient dissimilation’ (Jatteau & Hejná 2016) for the diachronic implementation of dissimilation. Since this sound change is usually considered as typically sporadic, lexically regular cases should result from lexical diffusion. In contrast with this ass......This paper explores the implications of ‘gradient dissimilation’ (Jatteau & Hejná 2016) for the diachronic implementation of dissimilation. Since this sound change is usually considered as typically sporadic, lexically regular cases should result from lexical diffusion. In contrast...... with this assumption, we explore the hypothesis that gradient dissimilation may represent the phonetic precursor of completed, regular dissimilatory processes. Such cases of dissimilation might then be reanalysed as Neogrammarian types of change. To assess this question, we gather and analyse new data from Halh...... Mongolian, a language reported to show gradient dissimilation (Svantesson et al. 2005), and compare it to two completed patterns of dissimilation reconstructed within the Mongolic family: Mongolian Chahar and Monguor. The results suggest that the gradient dissimilation in Halh may represent the phonetic...

Verbal expressions used by anaclitic and introjective patients with depressive symptomatology: Analysis of change and stuck episodes within therapeutic sessions

Directory of Open Access Journals (Sweden)

Nelson Valdés

2015-01-01

Full Text Available A person’s speech makes it possible to identify significant indicators which reflect certain characteristics of his/her personality organization, but also can vary depending on the relevance of specific moments of the session and the symptoms type. The present study analyzed 10 completed and successful therapeutic processes using a mixed methodology. The therapies were video–and audio-taped, as well as observed through a one-way mirror by trained observers. All the sessions of each therapy were considered (N = 230 in order to identify, delimit, transcribe, and analyze Change Episodes (CEs = 24 and Stuck Episodes (SEs = 26. Each episode was made up by patients’ speech segments (N = 1,282, which were considered as the sampling unit. The Therapeutic Activity Coding System (TACS-1.0 was used to manually code each patient’s verbalizations, nested within episodes and individuals, in order to analyze them using Hierarchical Linear Modelling (HLM. The findings suggest that anaclitic patients tend to use more verbalizations in order to ask for feedback or to be understood by their therapists (attune, whereas introjective patients tend to use more verbalizations in order to construct new meanings (resignify during therapeutic conversation, but especially during SEs. Clinical implications to enrich the therapeutic practice are discussed.

How do the features of mindfulness-based cognitive therapy contribute to positive therapeutic change? A meta-synthesis of qualitative studies.

Science.gov (United States)

Cairns, Victoria; Murray, Craig

2015-05-01

The exploration of Mindfulness-based Cognitive Therapy through qualitative investigation is a growing area of interest within current literature, providing valuable understanding of the process of change experienced by those engaging in this therapeutic approach. This meta-synthesis aims to gain a deeper understanding of how the features of Mindfulness-based Cognitive Therapy contribute to positive therapeutic change. Noblit and Hare's (1988) 7-step meta-ethnography method was conducted in order to synthesize the findings of seven qualitative studies. The process of reciprocal translation identified the following five major themes: i) Taking control through understanding, awareness and acceptance; ii) The impact of the group; (iii) Taking skills into everyday life; (iv) Feelings towards the self; (v) The role of expectations. The synthesis of translation identified the higher order concept of "The Mindfulness-based Cognitive Therapy Journey to Change", which depicts the complex interaction between the five themes in relation to how they contribute to positive therapeutic change. The findings are discussed in relation to previous research, theory and their implications for clinical practice.

ULK1: a promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma.

Directory of Open Access Journals (Sweden)

Miao Yun

Full Text Available Plenty of studies have established that dysregulation of autophagy plays an essential role in cancer progression. The autophagy-related proteins have been reported to be closely associated with human cancer patients' prognosis. We explored the expression dynamics and prognostic value of autophagy-related protein ULK1 by immunochemistry (IHC method in two independent cohorts of nasopharygeal carcinoma (NPC cases. The X-tile program was applied to determine the optimal cut-off value in the training cohort. This derived cutoff value was then subjected to analysis the association of ULK1 expression with patients' clinical characteristics and survival outcome in the validation cohort and overall cases. High ULK1 expression was closely associated with aggressive clinical feature of NPC patients. Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group. Our univariate and multivariate analysis also showed that higher ULK1 expression predicted inferior disease-specific survival (DSS (P<0.05. Consequently, a new clinicopathologic prognostic model with 3 poor prognostic factors (ie, ULK1 expression, overall clinical stage and therapeutic response could significantly stratify risk (low, intermediate and high for DSS in NPC patients (P<0.001. These findings provide evidence that, the examination of ULK1 expression by IHC method, could serve as an effective additional tool for predicting therapeutic response and patients' survival outcome in NPC patients.

Therapeutic applications of radiopharmaceuticals

International Nuclear Information System (INIS)

Baker, W.J.; Datz, F.L.; Beightol, R.W.

1987-01-01

Whether a radiopharmaceutical has diagnostic or therapeutic application depends on both the isotope and pharmaceutical used. For diagnostic applications, the isotope should undergo only γ-decay, since usually only γ-radiation is detected by nuclear medicine cameras. The half-life should be just long enough to allow the procedure to be performed. In contrast, the isotope needed for therapeutic purposes should have particulate radiation, such as a β-particle (electron), since these are locally absorbed an increase the local radiation dose. γ-Radiation, which penetrates the tissues, produces less radiation dose than do Β-particles. Several references dealing with radioactive decay, particulate interactions, and diagnostic and therapeutic applications of radiopharmaceuticals are available. Radiopharmaceuticals can legally be used only by physicians who are qualified by specific training in the safe handling of radionuclides. The experience and training of these physicians must be approved by the Nuclear Regulatory Commission or Agreement State Agency authorized to license the use of radiopharmaceuticals. A list of all byproduct material and procedures is available in the Code of Federal Regulations. Of the many radiopharmaceuticals available for diagnostic and therapeutic use, only those commonly used are discussed in this chapter

Severe hypertriglyceridemia. Clinical characteristics and therapeutic management.

Science.gov (United States)

Masson, Walter; Rossi, Emiliano; Siniawski, Daniel; Damonte, Juan; Halsband, Ana; Barolo, Ramiro; Scaramal, Miguel

2018-05-19

The therapeutic management of severe hypertriglyceridaemia represents a clinical challenge. The objectives of this study were 1) to identify the clinical characteristics of patients with severe hypertriglyceridaemia, and 2) to analyse the treatment established by the physicians in each case. A cross-sectional study was carried out using the computerised medical records of all patients>18 years of age with a blood triglyceride level≥1,000mg/dL between 1 January 2011 and 31 December 2016. Clinical and laboratory variables were collected. The behaviour of the physicians in the 6 months after the lipid finding was analysed. A total of 420 patients were included (mean age 49.1±11.4 years, males 78.8%). The median of triglycerides was 1,329mg/dL (interquartile range 1,174-1,658). No secondary causes were found in 34.1% of the patients. The most frequent secondary causes were obesity (38.6%) and diabetes (28.1%). Physical activity was recommended and a nutritionist was referred to in 49.1% and 44.2% of the patients, respectively. Secondary causes were identified and attempts were made to correct them in 40.7% of cases. The most indicated pharmacological treatments were fenofibrate 200mg/day (26.5%) and gemfibrozil 900mg/day (19.3%). Few patients received the indication of omega 3 fatty acids or niacin. This study showed, for the first time in our country, the characteristics of a population with severe hypertriglyceridaemia. The therapeutic measures instituted by the physicians were insufficient. Knowing the characteristics in this particular clinical scenario could improve the current approach of these patients. Copyright © 2018 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Differential solubility of curcuminoids in serum and albumin solutions: implications for analytical and therapeutic applications

Directory of Open Access Journals (Sweden)

Quitschke Wolfgang W

2008-11-01

Full Text Available Abstract Background Commercially available curcumin preparations contain a mixture of related polyphenols, collectively referred to as curcuminoids. These encompass the primary component curcumin along with its co-purified derivatives demethoxycurcumin and bisdemethoxycurcumin. Curcuminoids have numerous biological activities, including inhibition of cancer related cell proliferation and reduction of amyloid plaque formation associated with Alzheimer disease. Unfortunately, the solubility of curcuminoids in aqueous solutions is exceedingly low. This restricts their systemic availability in orally administered formulations and limits their therapeutic potential. Results Methods are described that achieve high concentrations of soluble curcuminoids in serum. Solid curcuminoids were either mixed directly with serum, or they were predissolved in dimethyl sulfoxide and added as aliquots to serum. Both methods resulted in high levels of curcuminoid-solubility in mammalian sera from different species. However, adding aliquots of dimethyl sulfoxide-dissolved curcuminoids to serum proved to be more efficient, producing soluble curcuminoid concentrations of at least 3 mM in human serum. The methods also resulted in the differential solubility of individual curcuminoids in serum. The addition of dimethyl sulfoxide-dissolved curcuminoids to serum preferentially solubilized curcumin, whereas adding solid curcuminoids predominantly solubilized bisdemethoxycurcumin. Either method of solubilization was equally effective in inhibiting dose-dependent HeLa cell proliferation in culture. The maximum concentration of curcuminoids achieved in serum was at least 100-fold higher than that required for inhibiting cell proliferation in culture and 1000-fold higher than the concentration that has been reported to prevent amyloid plaque formation associated with Alzheimer disease. Curcuminoids were also highly soluble in solutions of purified albumin, a major component of

Contemplating case mix: A primer on case mix classification and management.

Science.gov (United States)

Costa, Andrew P; Poss, Jeffery W; McKillop, Ian

2015-01-01

Case mix classifications are the frameworks that underlie many healthcare funding schemes, including the so-called activity-based funding. Now more than ever, Canadian healthcare administrators are evaluating case mix-based funding and deciphering how they will influence their organization. Case mix is a topic fraught with technical jargon and largely relegated to government agencies or private industries. This article provides an abridged review of case mix classification as well as its implications for management in healthcare. © 2015 The Canadian College of Health Leaders.

Massive hemoptysis in a patient with pulmonary embolism, a real therapeutic conundrum

Directory of Open Access Journals (Sweden)

Yiolanda Herodotou

2017-01-01

Full Text Available Massive Hemoptysis and pulmonary embolism are two very severe and potentially fatal pulmonary emergencies requiring completely different treatments. We present the case of a 45-year old male transmitted to our Hospital for massive hemoptysis who at the same time was found to suffer from pulmonary embolism. Hemoptysis was treated with bronchial artery embolization which resulted in cessation of haemorrhage and allowed the administration of anticoagulant therapy a few days later. This case report gives an answer on how to manage a real therapeutic conundrum which is the coexistence of a massive hemoptysis and a concomitant pulmonary embolism.

Therapeutic hypothermia for acute stroke

DEFF Research Database (Denmark)

Olsen, Tom Skyhøj; Weber, Uno Jakob; Kammersgaard, Lars Peter

2003-01-01

Experimental evidence and clinical experience show that hypothermia protects the brain from damage during ischaemia. There is a growing hope that the prevention of fever in stroke will improve outcome and that hypothermia may be a therapeutic option for the treatment of stroke. Body temperature...... obvious therapeutic potential, hypothermia as a form of neuroprotection for stroke has been investigated in only a few very small studies. Therapeutic hypothermia is feasible in acute stroke but owing to serious side-effects--such as hypotension, cardiac arrhythmia, and pneumonia--it is still thought...

Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic

Science.gov (United States)

Krystal, John H.; Abdallah, Chadi G.; Averill, Lynette A.; Kelmendi, Benjamin; Harpaz-Rotem, Ilan; Sanacora, Gerard; Southwick, Steven M.; Duman, Ronald S.

2018-01-01

Purpose of Review Studies of the neurobiology and treatment of PTSD have highlighted many aspects of the pathophysiology of this disorder that might be relevant to treatment. The purpose of this review is to highlight the potential clinical importance of an often-neglected consequence of stress models in animals that may be relevant to PTSD: the stress-related loss of synaptic connectivity. Recent Findings Here, we will briefly review evidence that PTSD might be a “synaptic disconnection syndrome” and highlight the importance of this perspective for the emerging therapeutic application of ketamine as a potential rapid-acting treatment for this disorder that may work, in part, by restoring synaptic connectivity. Summary Synaptic disconnection may contribute to the profile of PTSD symptoms that may be targeted by novel pharmacotherapeutics. PMID:28844076

Therapeutic Targeting of CPT-11 Induced Diarrhea: A Case for Prophylaxis

Science.gov (United States)

Swami, Umang; Goel, Sanjay; Mani, Sridhar

2014-01-01

CPT-11 (irinotecan), a DNA topoisomerase I inhibitor is one of the main treatments for colorectal cancer. The main dose limiting toxicities are neutropenia and late onset diarrhea. Though neutropenia is manageable, CPT-11 induced diarrhea is frequently severe, resulting in hospitalizations, dose reductions or omissions leading to ineffective treatment administration. Many potential agents have been tested in preclinical and clinical studies to prevent or ameliorate CPT-11 induced late onset diarrhea. It is predicted that prophylaxis of CPT-11 induced diarrhea will reduce sub-therapeutic dosing as well as hospitalizations and will eventually lead to dose escalations resulting in better response rates. This article reviews various experimental agents and strategies employed to prevent this debilitating toxicity. Covered topics include schedule/dose modification, intestinal alkalization, structural/chemical modification, genetic testing, anti-diarrheal therapies, transporter (ABCB1, ABCC2, BCRP2) inhibitors, enzyme (β-glucuronidase, UGT1A1, CYP3A4, carboxylesterase, COX-2) inducers and inhibitors, probiotics, antibiotics, adsorbing agents, cytokine and growth factor activators and inhibitors and other miscellaneous agents. PMID:23597015

Excitatory/inhibitory imbalance in autism spectrum disorders: Implications for interventions and therapeutics.

Science.gov (United States)

Uzunova, Genoveva; Pallanti, Stefano; Hollander, Eric

2016-04-01

Imbalance between excitation and inhibition and increased excitatory-inhibitory (E-I) ratio is a common mechanism in autism spectrum disorders (ASD) that is responsible for the learning and memory, cognitive, sensory, motor deficits, and seizures occurring in these disorders. ASD are very heterogeneous and better understanding of E-I imbalance in brain will lead to better diagnosis and treatments. We perform a critical literature review of the causes and presentations of E-I imbalance in ASD. E-I imbalance in ASD is due primarily to abnormal glutamatergic and GABAergic neurotransmission in key brain regions such as neocortex, hippocampus, amygdala, and cerebellum. Other causes are due to dysfunction of neuropeptides (oxytocin), synaptic proteins (neuroligins), and immune system molecules (cytokines). At the neuropathological level E-I imbalance in ASD is presented as a "minicolumnopathy". E-I imbalance alters the manner by which the brain processes information and regulates behaviour. New developments for investigating E-I imbalance such as optogenetics and transcranial magnetic stimulation (TMS) are presented. Non-invasive brain stimulation methods such as TMS for treatment of the core symptoms of ASD are discussed. Understanding E-I imbalance has important implications for developing better pharmacological and behavioural treatments for ASD, including TMS, new drugs, biomarkers and patient stratification.