Approach to Peripheral Neuropathy for the Primary Care Clinician.

PubMed

Doughty, Christopher T; Seyedsadjadi, Reza

2018-02-02

Peripheral neuropathy is commonly encountered in the primary care setting and is associated with significant morbidity, including neuropathic pain, falls, and disability. The clinical presentation of neuropathy is diverse, with possible symptoms including weakness, sensory abnormalities, and autonomic dysfunction. Accordingly, the primary care clinician must be comfortable using the neurologic examination-including the assessment of motor function, multiple sensory modalities, and deep tendon reflexes-to recognize and characterize neuropathy. Although the causes of peripheral neuropathy are numerous and diverse, careful review of the medical and family history coupled with limited, select laboratory testing can often efficiently lead to an etiologic diagnosis. This review offers an approach for evaluating suspected neuropathy in the primary care setting. It will describe the most common causes, suggest an evidence-based workup to aid in diagnosis, and highlight recent evidence that allows for selection of symptomatic treatment of patients with neuropathy. Copyright © 2018 Elsevier Inc. All rights reserved.

Neutrophil Recruitment and Articular Hyperalgesia in Antigen-Induced Arthritis are Modulated by the Cholinergic Anti-Inflammatory Pathway.

PubMed

Kanashiro, Alexandre; Talbot, Jhimmy; Peres, Raphael S; Pinto, Larissa G; Bassi, Gabriel S; Cunha, Thiago M; Cunha, Fernando Q

2016-11-01

The cholinergic anti-inflammatory pathway (CAP) is a complex neuroimmune mechanism triggered by the central nervous system to regulate peripheral inflammatory responses. Understanding the role of CAP in the pathogenesis of rheumatoid arthritis (RA) could help develop new therapeutic strategies for this disease. Therefore, we investigated the participation of this neuroimmune pathway on the progression of experimental arthritis. Using antigen-induced arthritis (AIA) model, we investigated in mice the effects of vagotomy or the pharmacological treatments with hexamethonium (peripheral nicotinic receptor antagonist), methylatropine (peripheral muscarinic receptor antagonist) or neostigmine (peripheral acetylcholinesterase inhibitor) on AIA progression. Unilateral cervical vagotomy was performed 1 week before the immunization protocol with methylated bovine serum albumin (mBSA), while drug administration was conducted during the period of immunization. On day 21, 6 hr after the challenge with mBSA injection in the femur-tibial joint, the local neutrophil migration and articular mechanical hyperalgesia were assessed. Herein, we observed that vagotomy or blockade of peripheral nicotinic (but not muscarinic) receptors exacerbated the clinical parameters of this disease. Moreover, peripheral acetylcholinesterase inhibition by neostigmine treatment promoted a reduction of neutrophil recruitment in the knee joint and articular hyperalgesia. Our results demonstrated that peripheral activation of CAP modulates experimental arthritis, providing a pre-clinical evidence of a potential therapeutic strategy for RA. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

An integrated nanotechnology-enabled transbronchial image-guided intervention strategy for peripheral lung cancer

PubMed Central

Jin, Cheng S.; Wada, Hironobu; Anayama, Takashi; McVeigh, Patrick Z; Hu, Hsin Pei; Hirohashi, Kentaro; Nakajima, Takahiro; Kato, Tatsuya; Keshavjee, Shaf; Hwang, David; Wilson, Brian C.; Zheng, Gang; Yasufuku, Kazuhiro

2016-01-01

Early detection and efficient treatment modality of early-stage peripheral lung cancer is essential. Current non-surgical treatments for peripheral lung cancer show critical limitations associated with various complications, requiring alternative minimally invasive therapeutics. Porphysome nanoparticle-enabled fluorescence-guided transbronchial photothermal therapy (PTT) of peripheral lung cancer was developed and demonstrated in preclinical animal models. Systemically-administered porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast, as confirmed in three subtypes of orthotopic human lung cancer xenografts (A549, H460 and H520) in mice and in an orthotopic VX2 tumor in rabbits. An in-house prototype fluorescence bronchoscope demonstrated the capability of porphysomes for in vivo imaging of lung tumors in the mucosal/submucosal layers, providing real-time fluorescence guidance for transbronchial PTT. Porphysomes also enhanced the efficacy of transbronchial PTT significantly and resulted in selective and efficient tumor tissue ablation in the rabbit model. A clinically used cylindrical diffuser fiber successfully achieved tumor-specific thermal ablation, showing promising evidence for the clinical translation of this novel platform to impact upon non-surgical treatment of early-stage peripheral lung cancer. PMID:27543602

Clinical practice guidelines on the evidence-based use of integrative therapies during and after breast cancer treatment.

PubMed

Greenlee, Heather; DuPont-Reyes, Melissa J; Balneaves, Lynda G; Carlson, Linda E; Cohen, Misha R; Deng, Gary; Johnson, Jillian A; Mumber, Matthew; Seely, Dugald; Zick, Suzanna M; Boyce, Lindsay M; Tripathy, Debu

2017-05-06

Answer questions and earn CME/CNE Patients with breast cancer commonly use complementary and integrative therapies as supportive care during cancer treatment and to manage treatment-related side effects. However, evidence supporting the use of such therapies in the oncology setting is limited. This report provides updated clinical practice guidelines from the Society for Integrative Oncology on the use of integrative therapies for specific clinical indications during and after breast cancer treatment, including anxiety/stress, depression/mood disorders, fatigue, quality of life/physical functioning, chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Clinical practice guidelines are based on a systematic literature review from 1990 through 2015. Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced nausea and vomiting. Acetyl-L-carnitine is not recommended to prevent chemotherapy-induced peripheral neuropathy due to a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatment-related side effects. In summary, there is a growing body of evidence supporting the use of integrative therapies, especially mind-body therapies, as effective supportive care strategies during breast cancer treatment. Many integrative practices, however, remain understudied, with insufficient evidence to be definitively recommended or avoided. CA Cancer J Clin 2017;67:194-232. © 2017 American Cancer Society. © 2017 American Cancer Society.

Multinational evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative.

PubMed

Machado, P; Castrejon, I; Katchamart, W; Koevoets, R; Kuriya, B; Schoels, M; Silva-Fernández, L; Thevissen, K; Vercoutere, W; Villeneuve, E; Aletaha, D; Carmona, L; Landewé, R; van der Heijde, D; Bijlsma, J W J; Bykerk, V; Canhão, H; Catrina, A I; Durez, P; Edwards, C J; Mjaavatten, M D; Leeb, B F; Losada, B; Martín-Mola, E M; Martinez-Osuna, P; Montecucco, C; Müller-Ladner, U; Østergaard, M; Sheane, B; Xavier, R M; Zochling, J; Bombardier, C

2011-01-01

To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA). 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008-9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007-2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. A total of 39,756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA. Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use.

Improving patient safety during insertion of peripheral venous catheters: an observational intervention study.

PubMed

Kampf, Günter; Reise, Gesche; James, Claudia; Gittelbauer, Kirsten; Gosch, Jutta; Alpers, Birgit

2013-01-01

Peripheral venous catheters are frequently used in hospitalized patients but increase the risk of nosocomial bloodstream infection. Evidence-based guidelines describe specific steps that are known to reduce infection risk. However, the degree of guideline implementation in clinical practice is not known. The aim of this study was to determine the use of specific steps for insertion of peripheral venous catheters in clinical practice and to implement a multimodal intervention aimed at improving both compliance and the optimum order of the steps. The study was conducted at University Hospital Hamburg. An optimum procedure for inserting a peripheral venous catheter was defined based on three evidence-based guidelines (WHO, CDC, RKI) including five steps with 1A or 1B level of evidence: hand disinfection before patient contact, skin antisepsis of the puncture site, no palpation of treated puncture site, hand disinfection before aseptic procedure, and sterile dressing on the puncture site. A research nurse observed and recorded procedures for peripheral venous catheter insertion for healthcare workers in four different departments (endoscopy, central emergency admissions, pediatrics, and dermatology). A multimodal intervention with 5 elements was established (teaching session, dummy training, e-learning tool, tablet and poster, and direct feedback), followed by a second observation period. During the last observation week, participants evaluated the intervention. In the control period, 207 insertions were observed, and 202 in the intervention period. Compliance improved significantly for four of five steps (e.g., from 11.6% to 57.9% for hand disinfection before patient contact; p<0.001, chi-square test). Compliance with skin antisepsis of the puncture site was high before and after intervention (99.5% before and 99.0% after). Performance of specific steps in the correct order also improved (e.g., from 7.7% to 68.6% when three of five steps were done; p<0.001). The intervention was described as helpful by 46.8% of the participants, as neutral by 46.8%, and as disruptive by 6.4%. A multimodal strategy to improve both compliance with safety steps for peripheral venous catheter insertion and performance of an optimum procedure was effective and was regarded helpful by healthcare workers.

Ambient geothermal hydrogen sulfide exposure and peripheral neuropathy

PubMed Central

Pope, Karl; So, Yuen T.; Crane, Julian; Bates, Michael N.

2017-01-01

The mechanism of toxicity of hydrogen sulfide (H2S) gas is thought mainly to operate through effects on the nervous system. The gas has high acute toxicity, but whether chronic exposure causes effects, including peripheral neuropathy, is yet unclear. The city of Rotorua, New Zealand, sits on an active geothermal field and the population has some of the highest measured ambient H2S exposures. A previous study in Rotorua provided evidence that H2S is associated with peripheral neuropathy. Using clinical methods, the present study sought to investigate and possibly confirm this association in the Rotorua population. The study population comprised 1,635 adult residents of Rotorua, aged 18–65. Collected data relevant to the peripheral neuropathy investigation included symptoms, ankle stretch reflex, vibration sensitivity, as measured by the timed-tuning fork test and a Bio-Thesiometer (Bio-Medical Instrument Co., Ohio), and light touch sensitivity measured by monofilaments. An exposure metric, estimating time-weighted H2S exposure across the last 30 years was used. Principal components analysis was used to combine data across the various indicators of possible peripheral neuropathy. The main data analysis used linear regression to examine associations between the peripheral nerve function indicators and H2S exposure. None of the peripheral nerve function indicators were associated with H2S exposure, providing no evidence that H2S exposure at levels found in Rotorua is a cause of peripheral neuropathy. The earlier association between H2S exposure and peripheral neuropathy diagnoses may be attributable to the ecological study design used. The possibility that H2S exposure misclassification could account for the lack of association found cannot be entirely excluded. PMID:28223159

Ambient geothermal hydrogen sulfide exposure and peripheral neuropathy.

PubMed

Pope, Karl; So, Yuen T; Crane, Julian; Bates, Michael N

2017-05-01

The mechanism of toxicity of hydrogen sulfide (H 2 S) gas is thought mainly to operate through effects on the nervous system. The gas has high acute toxicity, but whether chronic exposure causes effects, including peripheral neuropathy, is yet unclear. The city of Rotorua, New Zealand, sits on an active geothermal field and the population has some of the highest measured ambient H 2 S exposures. A previous study in Rotorua provided evidence that H 2 S is associated with peripheral neuropathy. Using clinical methods, the present study sought to investigate and possibly confirm this association in the Rotorua population. The study population comprised 1635 adult residents of Rotorua, aged 18-65. Collected data relevant to the peripheral neuropathy investigation included symptoms, ankle stretch reflex, vibration sensitivity, as measured by the timed-tuning fork test and a Bio-Thesiometer (Bio-Medical Instrument Co., Ohio), and light touch sensitivity measured by monofilaments. An exposure metric, estimating time-weighted H 2 S exposure across the last 30 years was used. Principal components analysis was used to combine data across the various indicators of possible peripheral neuropathy. The main data analysis used linear regression to examine associations between the peripheral nerve function indicators and H 2 S exposure. None of the peripheral nerve function indicators were associated with H 2 S exposure, providing no evidence that H 2 S exposure at levels found in Rotorua is a cause of peripheral neuropathy. The earlier association between H 2 S exposure and peripheral neuropathy diagnoses may be attributable to the ecological study design used. The possibility that H 2 S exposure misclassification could account for the lack of association found cannot be entirely excluded. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of Aging on the Auditory System and Related Cognitive Functions: A Narrative Review

PubMed Central

Jayakody, Dona M. P.; Friedland, Peter L.; Martins, Ralph N.; Sohrabi, Hamid R.

2018-01-01

Age-related hearing loss (ARHL), presbycusis, is a chronic health condition that affects approximately one-third of the world's population. The peripheral and central hearing alterations associated with age-related hearing loss have a profound impact on perception of verbal and non-verbal auditory stimuli. The high prevalence of hearing loss in the older adults corresponds to the increased frequency of dementia in this population. Therefore, researchers have focused their attention on age-related central effects that occur independent of the peripheral hearing loss as well as central effects of peripheral hearing loss and its association with cognitive decline and dementia. Here we review the current evidence for the age-related changes of the peripheral and central auditory system and the relationship between hearing loss and pathological cognitive decline and dementia. Furthermore, there is a paucity of evidence on the relationship between ARHL and established biomarkers of Alzheimer's disease, as the most common cause of dementia. Such studies are critical to be able to consider any causal relationship between dementia and ARHL. While this narrative review will examine the pathophysiological alterations in both the peripheral and central auditory system and its clinical implications, the question remains unanswered whether hearing loss causes cognitive impairment or vice versa. PMID:29556173

Vasoreactivity in CADASIL: Comparison to structural MRI and neuropsychology.

PubMed

Moreton, Fiona C; Cullen, Breda; Delles, Christian; Santosh, Celestine; Gonzalez, Rosario L; Dani, Krishna; Muir, Keith W

2018-06-01

Impaired cerebrovascular reactivity precedes histological and clinical evidence of CADASIL in animal models. We aimed to more fully characterise peripheral and cerebral vascular function and reactivity in a cohort of adult CADASIL patients, and explore the associations of these with conventional clinical, imaging and neuropsychological measures. A total of 22 adults with CADASIL gave informed consent to participate in an exploratory study of vascular function in CADASIL. Clinical assessment, comprehensive vascular assessment, MRI and neuropsychological testing were conducted. We measured cerebral vasoreactivity with transcranial Doppler and arterial spin labelling MRI with hypercapnia challenge. Number and volume of lacunes, subcortical hyperintensity volume, microbleeds and normalised brain volume were assessed on MRI. Analysis was exploratory and examined the associations between different markers. Cerebrovascular reactivity measured by ASL correlated with peripheral vasoreactivity measured by flow mediated dilatation. Subjects with ≥5 lacunes were older, with higher carotid intima-media thickness and had impaired cerebral and peripheral vasoreactivity. Subjects with depressive symptoms, disability or delayed processing speed also showed a trend to impaired vasoreactivity. Impaired vasoreactivity and vascular dysfunction may play a significant role in the pathophysiology of CADASIL, and vascular assessments may be useful biomarkers of severity in both longitudinal and clinical trials.

Clinical correlates of the presence of the Asp816Val c-kit mutation in the peripheral blood mononuclear cells of patients with mastocytosis.

PubMed

Worobec, A S; Semere, T; Nagata, H; Metcalfe, D D

1998-11-15

The Asp816Val mutation in the catalytic domain of the c-kit receptor has been identified in patients with systemic mastocytosis. To determine whether this mutation is associated with identifiable clinical patterns of disease and prognosis, a total of 65 patients with mastocytosis were screened for the presence of the Asp816Val mutation in peripheral blood mononuclear cells (PBMCs). By analysis of HinfI digestion products, the authors found that the overall prevalence of this mutation in the current patient series was 25%. The presence of the Asp816Val mutation in PBMCs was observed in 15 adults (of 16 Asp816Val mutation positive patients) and 1 infant, but not in any children with mastocytosis. Patients whose PBMCs were positive for this mutation (category II and a subset of category Ib mastocytosis patients) manifested a more severe disease pattern, with clinical features ranging in severity from early to advanced myelodysplastic or myeloproliferative syndromes. These patients more commonly had osteosclerotic bone involvement (a clinical feature primarily observed in mastocytosis patients with an associated hematologic disorder) as well as immunoglobulin dysregulation and peripheral blood abnormalities. Furthermore, pedigree analysis of three families provided evidence that the mutation was somatic. Twenty-five percent of all patients with mastocytosis had the Asp816Val mutation in PBMCs; 56% of these patients had evidence of a myelodysplastic or myeloproliferative syndrome, and 44% had been clinically placed in the indolent mastocytosis category, suggesting that the current classification scheme used to assign prognosis may be inadequate. Therefore, determination of the presence or absence of this mutation in PBMCs of mastocytosis patients offers a useful adjunct in determining the extent of workup and assigning prognosis in this complex and heterogeneous disease.

[SICI-GISE position paper on the requirements for diagnostic and interventional procedures in patients with peripheral arterial disease].

PubMed

Cremonesi, Alberto; Setacci, Carlo; Rubino, Paolo; Stabile, Eugenio; Castriota, Fausto; Reimers, Bernhard; Inglese, Luigi; Berti, Sergio; Sbarzaglia, Paolo; Biamino, Giancarlo; Guagliumi, Giulio

2013-10-01

Interventional procedures on peripheral vessels are the field of a novel specialty dedicated to the diagnosis and minimally invasive endovascular treatment of diseases involving the cerebral, thoracic and abdominal arteries (including renal and visceral arteries), as well as the peripheral arteries (femoro-popliteal arteries and the arteries below the knee). At present, physicians with three different types of medical training, each involving particular strengths and characteristics, specialize in endovascular treatment of patients with peripheral arterial disease: vascular surgeons, interventional radiologists and interventional cardiologists. Treatment of high-risk patients in terms of anatomical and clinical (serious comorbidities) complexity raised the need for the interventional cardiologist to face issues related to technical aspects of the procedure, multilevel pathology management and adequate indication. To achieve this goal, interventional cardiologists require particular facilities and clinical skills. The objectives of this position paper from the Italian Society of Interventional Cardiology (SICI-GISE) are (i) to define the theoretical background and practical training required to ensure that interventional cardiologists maintain high-quality standards also in the field of treatment of peripheral arterial disease, by establishing shared rules and drafting papers; (ii) to standardize the procedures of interventional cardiology operational units that treat patients with peripheral arterial disease in Italy on the basis of scientific evidence, and (iii) to establish common requirements in terms of facilities and regulations.

Mobile phone generated vibrations used to detect diabetic peripheral neuropathy.

PubMed

May, Jonathan David; Morris, Matthew William John

2017-12-01

In the current United Kingdom population the incidence of diabetic peripheral neuropathy is increasing. The presence of diabetic neuropathy affects decision making and treatment options. This study seeks to evaluate if the vibrations generated from a mobile phone can be used to screen patients for diabetic peripheral neuropathy. This study comprised of 61 patients; a control group of 21 patients; a lower limb injury group of 19 patients; a diabetic peripheral neuropathy group of 21 patients. The control and injury group were recruited randomly from fracture clinics. The diabetic peripheral neuropathy group were randomly recruited from the diabetic foot clinic. The 61 patients were examined using a 10g Semmes-Weinstein monofilament, a 128Hz tuning fork and a vibrating mobile phone. The points tested were, index finger, patella, lateral malleoli, medial malleoli, heel, first and fifth metatarsal heads. The most accurate location of all the clinical tests was the head of the 1st metatarsal at 0.86. The overall accuracy of the tuning fork was 0.77, the ten gram monofilament 0.79 and the mobile phone accuracy was 0.88. The control group felt 420 of 441 tests (95%). The injury group felt 349 of 399 tests (87%). The neuropathic group felt 216 of 441 tests (48%). There is a significant difference in the number of tests felt between the control and both the injury and neuropathic groups. p<0.0001 using N-1 Two Proportion Test. A mobile phone is an accurate screening tool for diabetic peripheral neuropathy. The most accurate location to test for diabetic peripheral neuropathy is the head of the 1st metatarsal. Screening for diabetic peripheral neuropathy in the index finger and patella were inaccurate. An injury to the lower limb affects the patient's vibration sensation, we would therefore recommend screening the contralateral limb to the injury. This study represents level II evidence of a new diagnostic investigation. Copyright © 2016 European Foot and Ankle Society. All rights reserved.

Multinational evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative

PubMed Central

Machado, P; Castrejon, I; Katchamart, W; Koevoets, R; Kuriya, B; Schoels, M; Silva-Fernández, L; Thevissen, K; Vercoutere, W; Villeneuve, E; Aletaha, D; Carmona, L; Landewé, R; van der Heijde, D; Bijlsma, J W J; Bykerk, V; Canhão, H; Catrina, A I; Durez, P; Edwards, C J; Mjaavatten, M D; Leeb, B F; Losada, B; Martín-Mola, E M; Martinez-Osuna, P; Montecucco, C; Müller-Ladner, U; Østergaard, M; Sheane, B; Xavier, R M; Zochling, J; Bombardier, C

2011-01-01

Objective To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA). Methods 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008–9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007–2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. Results A total of 39 756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA. Conclusions Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use. PMID:20724311

Toward an effective peripheral visceral analgesic: responding to the national opioid crisis.

PubMed

Camilleri, Michael

2018-06-01

This minireiew summarizes recent new developments in visceral analgesics. This promising field is important, as a new approach to address abdominal pain with peripheral visceral analgesics is considered a key approach to addressing the current opioid crisis. Some of the novel compounds address peripheral pain mechanisms through modulation of opioid receptors via biased ligands, nociceptin/orphanin FQ opioid peptide (NOP) receptor, or dual action on NOP and μ-opioid receptor, buprenorphine and morphiceptin analogs. Other compounds target nonopioid mechanisms, including cannabinoid (CB2), N-methyl-d-aspartate, calcitonin gene-related peptide, estrogen, and adenosine A 2B receptors and transient receptor potential (TRP) channels (TRPV1, TRPV4, and TRPM8). Although current evidence is based predominantly on animal models of visceral pain, early human studies also support the evidence from the basic and animal research. This augurs well for the development of nonaddictive, visceral analgesics for treatment of chronic abdominal pain, an unmet clinical need.

Cytokines and brain excitability

PubMed Central

Galic, Michael A.; Riazi, Kiarash; Pittman, Quentin J.

2012-01-01

Cytokines are molecules secreted by peripheral immune cells, microglia, astrocytes and neurons in the central nervous system. Peripheral or central inflammation is characterized by an upregulation of cytokines and their receptors in the brain. Emerging evidence indicates that pro-inflammatory cytokines modulate brain excitability. Findings from both the clinical literature and from in vivo and in vitro laboratory studies suggest that cytokines can increase seizure susceptibility and may be involved in epileptogenesis. Cellular mechanisms that underlie these effects include upregulation of excitatory glutamatergic transmission and downregulation of inhibitory GABAergic transmission. PMID:22214786

The hormonal control of ejaculation.

PubMed

Corona, Giovanni; Jannini, Emmanuele A; Vignozzi, Linda; Rastrelli, Giulia; Maggi, Mario

2012-09-01

Hormones regulate all aspects of male reproduction, from sperm production to sexual drive. Although emerging evidence from animal models and small clinical studies in humans clearly point to a role for several hormones in controlling the ejaculatory process, the exact endocrine mechanisms are unclear. Evidence shows that oxytocin is actively involved in regulating orgasm and ejaculation via peripheral, central and spinal mechanisms. Associations between delayed and premature ejaculation with hypothyroidism and hyperthyroidism, respectively, have also been extensively documented. Some models suggest that glucocorticoids are involved in the regulation of the ejaculatory reflex, but corresponding data from human studies are scant. Oestrogens regulate epididymal motility, whereas testosterone can affect the central and peripheral aspects of the ejaculatory process. Overall, the data of the endocrine system in regulating the ejaculatory reflex suggest that widely available endocrine therapies might be effective in treating sexual disorders in these men. Indeed, substantial evidence has documented that treatments of thyroid diseases are able to improve some ejaculatory difficulties.

Evidence from Human and Animal Studies: Pathological Roles of CD8+ T Cells in Autoimmune Peripheral Neuropathies

PubMed Central

Yang, Mu; Peyret, Corentin; Shi, Xiang Qun; Siron, Nicolas; Jang, Jeong Ho; Wu, Sonia; Fournier, Sylvie; Zhang, Ji

2015-01-01

Autoimmune peripheral neuropathies such as Guillain-Barre Syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4+ T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN). As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4+ T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicates that CD8+ T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8+ T cells in autoimmune peripheral neuropathies. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice) in which the T cell co-stimulator molecule B7.2 (CD86) is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8+ T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4+ T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8+ T cells in autoimmune peripheral neuropathies. PMID:26528293

Evidence from Human and Animal Studies: Pathological Roles of CD8(+) T Cells in Autoimmune Peripheral Neuropathies.

PubMed

Yang, Mu; Peyret, Corentin; Shi, Xiang Qun; Siron, Nicolas; Jang, Jeong Ho; Wu, Sonia; Fournier, Sylvie; Zhang, Ji

2015-01-01

Autoimmune peripheral neuropathies such as Guillain-Barre Syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4(+) T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN). As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4(+) T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicates that CD8(+) T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8(+) T cells in autoimmune peripheral neuropathies. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice) in which the T cell co-stimulator molecule B7.2 (CD86) is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8(+) T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4(+) T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8(+) T cells in autoimmune peripheral neuropathies.

A case with central and peripheral hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome) plus cataract.

PubMed

Sato, Ikuko; Onuma, Akira; Goto, Nobue; Sakai, Fumiaki; Fujiwara, Ikuma; Uematsu, Mitsugu; Osaka, Hitoshi; Okahashi, Satomi; Nonaka, Ikuya; Tanaka, Soichiro; Haginoya, Kazuhiro

2011-01-15

Hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome) is a rare disease, characterized by both central and peripheral hypomyelination. We describe a 21-year-old male with mildly progressive ataxia, mental retardation, pituitary hypogonadotropic hypogonadism, delayed dentition, and cataract. Brain magnetic resonance imaging showed hypomyelinated white matter, cerebellar atrophy, and a thin corpus callosum. The literature suggests that abnormal findings upon sural nerve biopsy may indicate peripheral hypomyelination, even in the absence of clinically and physiologically evident peripheral neuropathy. A sural nerve biopsy of this patient was normal, and this finding is further discussed. Taken together with previous reports, this case suggests that 4H syndrome can be regarded as a spectrum disorder, the cardinal signs of which may be central hypomyelination, ataxia, hypogonadotropic hypogonadism, and hypodontia. Copyright © 2010 Elsevier B.V. All rights reserved.

Improving patient safety during insertion of peripheral venous catheters: an observational intervention study

PubMed Central

Kampf, Günter; Reise, Gesche; James, Claudia; Gittelbauer, Kirsten; Gosch, Jutta; Alpers, Birgit

2013-01-01

Background: Peripheral venous catheters are frequently used in hospitalized patients but increase the risk of nosocomial bloodstream infection. Evidence-based guidelines describe specific steps that are known to reduce infection risk. However, the degree of guideline implementation in clinical practice is not known. The aim of this study was to determine the use of specific steps for insertion of peripheral venous catheters in clinical practice and to implement a multimodal intervention aimed at improving both compliance and the optimum order of the steps. Methods: The study was conducted at University Hospital Hamburg. An optimum procedure for inserting a peripheral venous catheter was defined based on three evidence-based guidelines (WHO, CDC, RKI) including five steps with 1A or 1B level of evidence: hand disinfection before patient contact, skin antisepsis of the puncture site, no palpation of treated puncture site, hand disinfection before aseptic procedure, and sterile dressing on the puncture site. A research nurse observed and recorded procedures for peripheral venous catheter insertion for healthcare workers in four different departments (endoscopy, central emergency admissions, pediatrics, and dermatology). A multimodal intervention with 5 elements was established (teaching session, dummy training, e-learning tool, tablet and poster, and direct feedback), followed by a second observation period. During the last observation week, participants evaluated the intervention. Results: In the control period, 207 insertions were observed, and 202 in the intervention period. Compliance improved significantly for four of five steps (e.g., from 11.6% to 57.9% for hand disinfection before patient contact; p<0.001, chi-square test). Compliance with skin antisepsis of the puncture site was high before and after intervention (99.5% before and 99.0% after). Performance of specific steps in the correct order also improved (e.g., from 7.7% to 68.6% when three of five steps were done; p<0.001). The intervention was described as helpful by 46.8% of the participants, as neutral by 46.8%, and as disruptive by 6.4%. Conclusions: A multimodal strategy to improve both compliance with safety steps for peripheral venous catheter insertion and performance of an optimum procedure was effective and was regarded helpful by healthcare workers. PMID:24327944

Frontal fibrosing alopecia associated with generalized hair loss.

PubMed

Armenores, Paul; Shirato, Kyoko; Reid, Catherine; Sidhu, Shireen

2010-08-01

We present six cases of frontal fibrosing alopecia, in which generalized hair loss is a feature. Although this variant of lichen planopilaris has been reported clinically in a number of patients, there is very little histological evidence that the condition exists in peripheral sites. We believe this pattern of involvement may be more common than is reported, and have provided histological evidence of lichen planopilaris being present at sites beyond the scalp and eyebrows.

Use of real-time PCR to rule out Marek's disease in the diagnosis of peripheral neuropathy.

PubMed

Gall, Sesny; Kőrösi, László; Cortes, Aneg L; Delvecchio, Andrea; Prandini, Francesco; Mitsch, Peter; Gimeno, Isabel M

2018-08-01

This article reports nine cases of neurological disease in brown layer pullets that occured in various European countries between 2015 and 2018. In all cases, the onset of neurological clinical signs was at 4-8 weeks of age and they lasted up to 22 weeks of age. Enlargement of peripheral nerves was the main lesion observed in all cases. Histopathological evaluation of nerves revealed oedema with moderate to severe infiltration of plasma cells. Marek's disease (MD) was ruled out by real-time PCR as none of the evaluated tissues had a high load of oncogenic MD virus (MDV) DNA, characteristics of MD. Based on the epidemiological data (layers with clinical signs starting at 5-8 weeks of age), gross lesions (peripheral nerve enlargement with a lack of tumours in other organs), histopathological lesions (oedema and infiltration of plasma cells), and no evidence of high load of MDV DNA, we concluded that those cases were due to peripheral neuropathy (PN). PN is an autoimmune disease easily misdiagnosed as MD, leading to a costly enforcement of the vaccination protocol. Additional vaccination against MD does not protect against PN and could worsen the clinical signs by over-stimulating the immune system. Differential diagnosis between PN and MD should always be considered in cases of neurological disease with enlargement of peripheral nerves as the only gross lesion. This case report shows for the first time how real-time PCR to detect oncogenic MDV is a very valuable tool in the differential diagnosis of PN and MD.

Combining Gene and Stem Cell Therapy for Peripheral Nerve Tissue Engineering.

PubMed

Busuttil, Francesca; Rahim, Ahad A; Phillips, James B

2017-02-15

Despite a substantially increased understanding of neuropathophysiology, insufficient functional recovery after peripheral nerve injury remains a significant clinical challenge. Nerve regeneration following injury is dependent on Schwann cells, the supporting cells in the peripheral nervous system. Following nerve injury, Schwann cells adopt a proregenerative phenotype, which supports and guides regenerating nerves. However, this phenotype may not persist long enough to ensure functional recovery. Tissue-engineered nerve repair devices containing therapeutic cells that maintain the appropriate phenotype may help enhance nerve regeneration. The combination of gene and cell therapy is an emerging experimental strategy that seeks to provide the optimal environment for axonal regeneration and reestablishment of functional circuits. This review aims to summarize current preclinical evidence with potential for future translation from bench to bedside.

Charcot Marie Tooth 2B Peripheral Sensory Neuropathy: How Rab7 Mutations Impact NGF Signaling?

PubMed

Liu, Harry; Wu, Chengbiao

2017-02-04

Charcot-Marie-Tooth 2B peripheral sensory neuropathy (CMT2B) is a debilitating autosomal dominant hereditary sensory neuropathy. Patients with this disease lose pain sensation and frequently need amputation. Axonal dysfunction and degeneration of peripheral sensory neurons is a major clinical manifestation of CMT2B. However, the cellular and molecular pathogenic mechanisms remain undefined. CMT2B is caused by missense point mutations (L129F, K157N, N161T/I, V162M) in Rab7 GTPase. Strong evidence suggests that the Rab7 mutation(s) enhances the cellular levels of activated Rab7 proteins, thus resulting in increased lysosomal activity and autophagy. As a consequence, trafficking and signaling of neurotrophic factors such as nerve growth factor (NGF) in the long axons of peripheral sensory neurons are particularly vulnerable to premature degradation. A "gain of toxicity" model has, thus, been proposed based on these observations. However, studies of fly photo-sensory neurons indicate that the Rab7 mutation(s) causes a "loss of function", resulting in haploinsufficiency. In the review, we summarize experimental evidence for both hypotheses. We argue that better models (rodent animals and human neurons) of CMT2B are needed to precisely define the disease mechanisms.

The Influence of Nicotine on Lung Tumor Growth, Cancer Chemotherapy, and Chemotherapy-Induced Peripheral Neuropathy.

PubMed

Kyte, S Lauren; Gewirtz, David A

2018-06-04

Studies in animal models have suggested that nicotine, an agonist of nicotinic acetylcholine receptors (nAChRs), may have the potential to prevent and/or reverse the peripheral neuropathy induced by cancer chemotherapeutic drugs, such as paclitaxel and oxaliplatin. However, a large body of evidence suggests that nicotine may also stimulate lung tumor growth and/or interfere with the effectiveness of cancer chemotherapy. While the reported proliferative effects of nicotine are highly variable, the antagonism of antitumor drug efficacy is more consistent, although this latter effect has been demonstrated primarily in cell culture studies. In contrast, in vitro and in vivo studies from our own laboratory indicate that nicotine fails to enhance the growth of non-small cell lung cancer cells or attenuate the effects of chemotherapy (paclitaxel). Given the inconsistencies in the literature, coupled with our own findings, the weight of evidence suggests that caution may be warranted in proposing to utilize nicotine to mitigate chemotherapy-induced peripheral neuropathy in cancer patients receiving chemotherapy. Conversely, clinical trials could be performed in patients who have completed therapy and are considered to be disease-free to determine whether nicotine, in the form of commercially available patches or gum, is effective in alleviating peripheral neuropathy symptoms. The American Society for Pharmacology and Experimental Therapeutics.

Diabetic neuropathy: Clinical manifestations and current treatments

PubMed Central

Callaghan, Brian C.; Cheng, Hsinlin; Stables, Catherine L.; Smith, Andrea L.; Feldman, Eva L.

2014-01-01

Diabetic peripheral neuropathy is a prevalent, disabling condition. The most common manifestation is a distal symmetric polyneuropathy (DSP), but many patterns of nerve injury can occur. Currently, the only effective treatments are glucose control and pain management. While glucose control dramatically decreases the development of neuropathy in those with type 1 diabetes, the effect is likely much smaller in those with type 2 diabetes. High levels of evidence support the use of certain anticonvulsants and antidepressants for pain management in diabetic peripheral neuropathy. However, the lack of disease modifying therapies for diabetic DSP makes the identification of new modifiable risk factors essential. Intriguingly, growing evidence supports an association between metabolic syndrome components, including pre-diabetes, and neuropathy. Future studies are needed to further explore this relationship with implications for new treatments for this common disease. PMID:22608666

Brain amyloidosis ascertainment from cognitive, imaging, and peripheral blood protein measures

PubMed Central

Hwang, Kristy S.; Avila, David; Elashoff, David; Kohannim, Omid; Teng, Edmond; Sokolow, Sophie; Jack, Clifford R.; Jagust, William J.; Shaw, Leslie; Trojanowski, John Q.; Weiner, Michael W.; Thompson, Paul M.

2015-01-01

Background: The goal of this study was to identify a clinical biomarker signature of brain amyloidosis in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) mild cognitive impairment (MCI) cohort. Methods: We developed a multimodal biomarker classifier for predicting brain amyloidosis using cognitive, imaging, and peripheral blood protein ADNI1 MCI data. We used CSF β-amyloid 1–42 (Aβ42) ≤192 pg/mL as proxy measure for Pittsburgh compound B (PiB)-PET standard uptake value ratio ≥1.5. We trained our classifier in the subcohort with CSF Aβ42 but no PiB-PET data and tested its performance in the subcohort with PiB-PET but no CSF Aβ42 data. We also examined the utility of our biomarker signature for predicting disease progression from MCI to Alzheimer dementia. Results: The CSF training classifier selected Mini-Mental State Examination, Trails B, Auditory Verbal Learning Test delayed recall, education, APOE genotype, interleukin 6 receptor, clusterin, and ApoE protein, and achieved leave-one-out accuracy of 85% (area under the curve [AUC] = 0.8). The PiB testing classifier achieved an AUC of 0.72, and when classifier self-tuning was allowed, AUC = 0.74. The 36-month disease-progression classifier achieved AUC = 0.75 and accuracy = 71%. Conclusions: Automated classifiers based on cognitive and peripheral blood protein variables can identify the presence of brain amyloidosis with a modest level of accuracy. Such methods could have implications for clinical trial design and enrollment in the near future. Classification of evidence: This study provides Class II evidence that a classification algorithm based on cognitive, imaging, and peripheral blood protein measures identifies patients with brain amyloid on PiB-PET with moderate accuracy (sensitivity 68%, specificity 78%). PMID:25609767

The role of nutrition and body composition in peripheral arterial disease

PubMed Central

Brostow, Diana P.; Hirsch, Alan T.; Collins, Tracie C.; Kurzer, Mindy S.

2015-01-01

Peripheral arterial disease (PAD) has not been as extensively investigated as other cardiovascular diseases. However, the available data suggest that nutrition-based treatment strategies have the potential to reduce the cost-economic burden of PAD substantially. Abdominal obesity is associated with PAD and prospective and cross-sectional studies have shown that a low dietary intake of folate and reduced synthesis of vitamin D are associated with an increased risk of PAD and severe walking impairment in patients who have the disease. However, dietary patterns that are associated with decreased cardiovascular risk might protect against PAD. A small number of clinical trials have provided evidence that increased intakes of niacin and insoluble fiber might be associated with decreased levels of LDL cholesterol and thrombogenic biomarkers, as well as increased serum levels of HDL cholesterol in patients with PAD. However, little evidence that antioxidants, vitamins B6 and B12, or essential fatty acid supplements improve clinical outcomes in these patients exists. Overall, data on the effects of nutrition, body composition, and nutritional supplementation on the risk, progression, and prognosis of PAD are scarce. Further research into these areas is required to allow the development of evidence-based nutritional guidelines for the prevention and treatment of the disease. PMID:22922595

Transcatheter Embolization of Peripheral Renal Artery for Hemorrhagic Urological Emergencies using FuAiLe Medical Glue

PubMed Central

An, Tianzhi; Zhang, Shasha; Xu, Min; Zhou, Shi; Wang, Weiping

2015-01-01

Our objective was to review the technical success and clinical outcomes of transcatheter embolization of peripheral renal artery with FuAiLe medical glue (FAL). All patients who underwent FAL embolization for peripheral renal artery bleeding were retrospectively analyzed for underlying pathologies, technical success and outcome of embolization procedure. 14 consecutive patients underwent FAL embolization between November 2009 and February 2013. The causes of bleeding were post biopsy (n = 5), blunt trauma (n = 5), percutaneous lithotripsy of kidney stones (n = 3), and complication of cardiac catheterization (n = 1). Bleeding was effectively controlled with a single injection of FAL. Mean volume of FAL mixture (FAL:Lipiodol, 1:1) was 0.5 mL (range, 0.2–0.8 mL). No reflux of the embolic agent was noted. Average cost of FAL for each procedure was $74. Postembolization clinical follow-up showed no evidence of recurrent hematuria, progression of hematoma, hypertension, or elevation of serum creatinine. Doppler ultrasound examinations in 13 patients demonstrated no abscess, renal parenchyma infarction, or renal artery abnormalities. Superselective FAL embolization may be used for the treatment of active bleeding from peripheral renal arteries. It has a high success rate and is quicker and less expensive than embolization with other agents. PMID:25765607

Transcatheter embolization of peripheral renal artery for hemorrhagic urological emergencies using FuAiLe medical glue.

PubMed

An, Tianzhi; Zhang, Shasha; Xu, Min; Zhou, Shi; Wang, Weiping

2015-03-13

Our objective was to review the technical success and clinical outcomes of transcatheter embolization of peripheral renal artery with FuAiLe medical glue (FAL). All patients who underwent FAL embolization for peripheral renal artery bleeding were retrospectively analyzed for underlying pathologies, technical success and outcome of embolization procedure. 14 consecutive patients underwent FAL embolization between November 2009 and February 2013. The causes of bleeding were post biopsy (n = 5), blunt trauma (n = 5), percutaneous lithotripsy of kidney stones (n = 3), and complication of cardiac catheterization (n = 1). Bleeding was effectively controlled with a single injection of FAL. Mean volume of FAL mixture (FAL:Lipiodol, 1:1) was 0.5 mL (range, 0.2-0.8 mL). No reflux of the embolic agent was noted. Average cost of FAL for each procedure was $74. Postembolization clinical follow-up showed no evidence of recurrent hematuria, progression of hematoma, hypertension, or elevation of serum creatinine. Doppler ultrasound examinations in 13 patients demonstrated no abscess, renal parenchyma infarction, or renal artery abnormalities. Superselective FAL embolization may be used for the treatment of active bleeding from peripheral renal arteries. It has a high success rate and is quicker and less expensive than embolization with other agents.

How to diagnose neuropathic pain? The contribution from clinical examination, pain questionnaires and diagnostic tests.

PubMed

La Cesa, S; Tamburin, S; Tugnoli, V; Sandrini, G; Paolucci, S; Lacerenza, M; Marchettini, P; Cruccu, G; Truini, A

2015-12-01

Patients with peripheral and central nervous system diseases may suffer from different types of pain, namely nociceptive, neuropathic and mixed pain. Although in some cases, the distinction between these types of pain is clinically evident, yet in some patients an accurate differential diagnosis requires dedicated clinical examination, screening questionnaires and diagnostic techniques some of which are available only in specialized pain centres. This review briefly addresses the currently agreed definitions of the different types of pain and shows how clinical examination, pain questionnaires and diagnostic tests can help the clinicians in identifying neuropathic pain.

Pilot Testing a Web-Based System for the Assessment and Management of Chemotherapy-Induced Peripheral Neuropathy.

PubMed

Knoerl, Robert; Dudley, William N; Smith, Gloria; Bridges, Celia; Kanzawa-Lee, Grace; Lavoie Smith, Ellen M

2017-04-01

Because numerous barriers hinder the assessment and management of chemotherapy-induced peripheral neuropathy in clinical practice, the Carevive Care Planning System, a novel Web-based platform, was developed to address these barriers. It provides patients an opportunity to report their symptoms before their clinic visit and generates customizable care plans composed of evidence-based management strategies. The purpose of this study was to evaluate patient and provider perspectives of feasibility, usability, acceptability, and satisfaction with the Carevive platform. We used a single-arm, pretest/posttest, prospective design and recruited 25 women with breast cancer who were receiving neurotoxic chemotherapy and six advanced practice providers from an academic hospital. At three consecutive clinical visits, patients reported their neuropathy symptoms on a tablet via the Carevive system. The Diffusion of Innovations Theory served as an overarching evaluation framework. The Carevive platform was feasible to use. However, patients had higher ratings of usability, acceptability, and satisfaction with the platform than did the providers, who disliked the amount of time required to use the platform and had difficulty logging into Carevive. If issues regarding provider dissatisfaction can be addressed, the Carevive platform may aid in the screening of neuropathy symptoms and facilitate the use of evidence-based management strategies.

Bupivacaine, levobupivacaine and ropivacaine: are they clinically different?

PubMed

Casati, Andrea; Putzu, Marta

2005-06-01

Two new, long-acting local anaesthetics have been developed after the evidence of bupivacaine-related severe toxicity: levobupivacaine and ropivacaine. Both these agents are pure left-isomers and, based on their three-dimensional structure, they have less toxic potential both on the central nervous system and on the heart. Several clinical studies have evaluated their toxicology and clinical profiles: theoretically and experimentally, some differences can be seen, but the reflections of these characteristics into clinical practice have not been evident. Evaluating randomised, controlled trials that have compared these three local anaesthetics, this chapter supports the evidence that both levobupivacaine and ropivacaine have a clinical profile similar to that of racemic bupivacaine, and that the minimal differences observed between the three agents are mainly related to the slightly different anaesthetic potency, with racemic bupivacaine>levobupivacaine>ropivacaine. However, the reduced toxic potential of the two pure left-isomers supports their use in those clinical situations in which the risk of systemic toxicity related to either overdosing or unwanted intravascular injection is high, such as during epidural or peripheral nerve blocks.

Celiac Disease Presenting with Peripheral Neuropathy in Children: A Case Report.

PubMed

Pacitto, Alessandra; Paglino, Alessandra; Di Genova, Lorenza; Leonardi, Alberto; Farinelli, Edoardo; Principi, Nicola; di Cara, Giuseppe; Esposito, Susanna

2017-07-14

Background: Clinically relevant neurological manifestations in children with celiac disease (CD) are unusual, especially when they are considered as signs of the onset of the disease. In this paper, a case of Guillain-Barrè syndrome (GBS) as the first manifestation of CD in a 23-month-old child is reported. Case presentation: We describe a case of CD onset with peripheral neuropathy in a 23-month-old Bulgarian boy presenting with a sudden refusal to walk and absence of deep tendon reflexes in both lower limbs. Neurological symptoms were preceded by two months of gastrointestinal symptoms such as vomiting, abdominal distention, and clear signs of malnutrition and weight loss. When we evaluated the child six months after the onset of the symptoms, clinical and laboratory findings showed clear signs of peripheral neuropathy associated with malnutrition. Serum deamidated gliadin and tissue transglutaminase antibodies were therefore measured. The anti-gliadin levels were more than sixteen times higher than normal and the IgA anti-transglutaminase levels were four times higher than normal. Anti-endomysium antibodies were positive, and human leukocyte antigens (HLA) II typing confirmed a genetic predisposition to CD (DQ2 positive and DQ8 negative). Given the association between the clinical evidence of the disease and the results of the celiac screening tests, a diagnosis of CD was made without biopsy confirmation of the enteropathy. The child began a restricted gluten-free diet that led to complete recovery of the peripheral neuropathy, walking, reflexes, and overall improvement after three months on the diet. Conclusion: Our case underlines the rare but possible associations between CD and peripheral neuropathy in children as an onset symptom, even in the absence of gastrointestinal manifestations, thus suggesting that CD should always be considered in the differential diagnosis of peripheral neuropathy in children. A good knowledge of the extra-intestinal manifestations of CD is essential for the rapid introduction of a gluten-free diet that could be useful for the resolution of the neurological symptoms.

Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair

PubMed Central

Sánchez, Mikel; Garate, Ane; Delgado, Diego; Padilla, Sabino

2017-01-01

Therapies such as direct tension-free microsurgical repair or transplantation of a nerve autograft, are nowadays used to treat traumatic peripheral nerve injuries (PNI), focused on the enhancement of the intrinsic regenerative potential of injured axons. However, these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases, the functional recovery of nerve injuries is incomplete. Thus, new biomedical engineering strategies based on tissue engineering approaches through molecular intervention and scaffolding offer promising outcomes on the field. In this sense, evidence is accumulating in both, preclinical and clinical settings, indicating that platelet-rich plasma products, and fibrin scaffold obtained from this technology, hold an important therapeutic potential as a neuroprotective, neurogenic and neuroinflammatory therapeutic modulator system, as well as enhancing the sensory and motor functional nerve muscle unit recovery. PMID:28250739

Analgesic efficacy of cerebral and peripheral electrical stimulation in chronic nonspecific low back pain: a randomized, double-blind, factorial clinical trial.

PubMed

Hazime, Fuad Ahmad; de Freitas, Diego Galace; Monteiro, Renan Lima; Maretto, Rafaela Lasso; Carvalho, Nilza Aparecida de Almeida; Hasue, Renata Hydee; João, Silvia Maria Amado

2015-01-31

Chronic non-specific low back pain is a major socioeconomic public health issue worldwide and, despite the volume of research in the area, it is still a difficult-to-treat condition. The conservative analgesic therapy usually comprises a variety of pharmacological and non-pharmacological strategies, such as transcutaneous electrical nerve stimulation. The neuromatrix pain model and the new findings on the process of chronicity of pain point to a higher effectiveness of treatments that address central rather than peripheral structures. The transcranial direct current stimulation is a noninvasive technique of neuromodulation that has made recent advances in the treatment of chronic pain. The simultaneous combination of these two electrostimulation techniques (cerebral and peripheral) can provide an analgesic effect superior to isolated interventions. However, all the evidence on the analgesic efficacy of these techniques, alone or combined, is still fragmented. This is a protocol for a randomized clinical trial to investigate whether cerebral electrical stimulation combined with peripheral electrical stimulation is more effective in relieving pain than the isolated application of electrical stimulations in patients with chronic nonspecific low back pain. Ninety-two patients will be randomized into four groups to receive transcranial direct current stimulation (real/sham) + transcutaneous electrical nerve stimulation (real/sham) for 12 sessions over a period of four weeks. The primary clinical outcome (pain intensity) and the secondary ones (sensory and affective aspects of pain, physical functioning and global perceived effect) will be recorded before treatment, after four weeks, in Month 3 and in Month 6 after randomization. Confounding factors such as anxiety and depression, the patient's satisfaction with treatment and adverse effects will also be listed. Data will be collected by an examiner unaware of (blind to) the treatment allocation. The results of this study may assist in clinical decision-making about the combined use of cerebral and peripheral electrical stimulation for pain relief in patients with chronic low back pain. NCT01896453.

Clinical use of closed-system safety peripheral intravenous cannulas.

PubMed

Barton, Andrew

2018-04-26

Peripheral intravenous (IV) cannulas are the quickest and most effective way of gaining venous vascular access and administering IV therapy. Closed-system peripheral IV cannulas have been shown to be safe and more reliable than open, non-valved peripheral cannulas in clinical practice. This article introduces the Smiths Medical DeltaVen closed-system peripheral IV cannula and includes three case studies describing its use in clinical practice and associated patient outcomes.

Retinoic acid reduces chemotherapy-induced neuropathy in an animal model and patients with lung cancer

PubMed Central

Hernández-Pedro, N.; Fernández-González- Aragón, M.C.; Saavedra-Pérez, D.; Campos-Parra, A.D.; Ríos-Trejo, M.Á.; Cerón-Lizárraga, T.; Martínez-Barrera, L.; Pineda, B.; Ordóñez, G.; Ortiz-Plata, A.; Granados-Soto, V.; Sotelo, J.

2011-01-01

Objective: To evaluate the effect of all-trans retinoic acid (ATRA) as treatment for chemotherapy-induced peripheral neuropathy in an experimental animal model and in a randomized, double-blinded, controlled trial in patients with non-small-cell lung cancer (NSCLC). Methods: Forty male Wistar rats were randomized in 5 groups: group A, control; groups B and C, treated with cisplatin; and groups D and E, treated with paclitaxel. ATRA (20 mg/kg PO) was administered for 15 days in groups C and E. We evaluated neuropathy and nerve regeneration–related morphologic changes in sciatic nerve, the concentration of nerve growth factor (NGF), and retinoic acid receptor (RAR)–α and RAR-β expression. In addition, 95 patients with NSCLC under chemotherapy treatment were randomized to either ATRA (20 mg/m2/d) or placebo. Serum NGF, neurophysiologic tests, and clinical neurotoxicity were assessed. Results: The experimental animals developed neuropathy and axonal degeneration, associated with decreased NGF levels in peripheral nerves. Treatment with ATRA reversed sensorial changes and nerve morphology; this was associated with increased NGF levels and RAR-β expression. Patients treated with chemotherapy had clinical neuropathy and axonal loss assessed by neurophysiology, which was related to decreased NGF levels. ATRA reduced axonal degeneration demonstrated by nerve conduction velocity and clinical manifestations of neuropathy grades ≥2. Conclusions: ATRA reduced chemotherapy-induced experimental neuropathy, increased NGF levels, and induced RAR-β expression in nerve. In patients, reduction of NGF in serum was associated with the severity of neuropathy; ATRA treatment reduced the electrophysiologic alterations. Classification of evidence: This study provides Class II evidence that ATRA improves nerve conduction in patients with chemotherapy-induced peripheral neuropathy. Neurology® 2011;77:987–995 PMID:21865574

Sodium Caseinate (CasNa) Induces Mobilization of Hematopoietic Stem Cells in a BALB/c Mouse Model

PubMed Central

Santiago-Osorio, Edelmiro; Ledesma-Martínez, Edgar; Aguiñiga-Sánchez, Itzen; Poblano-Pérez, Ignacio; Weiss-Steider, Benny; Montesinos-Montesinos, Juan José; de Lourdes Mora-García, María

2015-01-01

Background Hematopoietic stem cells transplantation has high clinical potential against a wide variety of hematologic, metabolic, and autoimmune diseases and solid tumors. Clinically, hematopoietic stem cells derived from peripheral blood are currently used more than those obtained from sources such as bone marrow. However, mobilizing agents used in the clinic tend to fail in high rates, making the number of mobilized cells insufficient for transplantation. We investigated whether sodium caseinate induces functional mobilization of hematopoietic stem cells into peripheral blood of Balb/c mice. Material/Methods Using a mouse model, we administrated sodium caseinate or Plerixafor, a commercial mobilizing agent, and analyzed counts of hematopoietic stem cells in peripheral blood, and then cells were transplanted into lethally irradiated mice to restore hematopoiesis. All assays were performed at least twice. Results We found that sodium caseinate increases the number of mononuclear cells in peripheral blood with the immunophenotype of hematopoietic stem cells (0.2 to 0.5% LSK cells), allowing them to form colonies of various cell lineages in semisolid medium (p<0.05). This effect is similar to that of Plerixafor, and cells transplanted into lethally irradiated mice can restore hematopoiesis at higher percentages than mononuclear cells mobilized by Plerixafor (40% vs. 20%, respectively). Further, a secondary transplant rescued a separate group of irradiated mice from death, proving definitive evidence of hematopoietic reconstitution after hematopoietic stem cells transplantation. Data are presented as mean ± standard deviation. To determine significant differences between the data, one-way ANOVA and the Tukey test were used. Conclusions Collectively these results show the utility of sodium caseinate as a mobilizer of hematopoietic stem cells and its potential clinical application in transplantation settings. PMID:26409928

Sodium Caseinate (CasNa) Induces Mobilization of Hematopoietic Stem Cells in a BALB/c Mouse Model.

PubMed

Santiago-Osorio, Edelmiro; Ledesma-Martínez, Edgar; Aguiñiga-Sánchez, Itzen; Poblano-Pérez, Ignacio; Weiss-Steider, Benny; Montesinos-Montesinos, Juan José; Mora-García, María de Lourdes

2015-09-25

BACKGROUND Hematopoietic stem cells transplantation has high clinical potential against a wide variety of hematologic, metabolic, and autoimmune diseases and solid tumors. Clinically, hematopoietic stem cells derived from peripheral blood are currently used more than those obtained from sources such as bone marrow. However, mobilizing agents used in the clinic tend to fail in high rates, making the number of mobilized cells insufficient for transplantation. We investigated whether sodium caseinate induces functional mobilization of hematopoietic stem cells into peripheral blood of Balb/c mice. MATERIAL AND METHODS Using a mouse model, we administrated sodium caseinate or Plerixafor, a commercial mobilizing agent, and analyzed counts of hematopoietic stem cells in peripheral blood, and then cells were transplanted into lethally irradiated mice to restore hematopoiesis. All assays were performed at least twice. RESULTS We found that sodium caseinate increases the number of mononuclear cells in peripheral blood with the immunophenotype of hematopoietic stem cells (0.2 to 0.5% LSK cells), allowing them to form colonies of various cell lineages in semisolid medium (p<0.05). This effect is similar to that of Plerixafor, and cells transplanted into lethally irradiated mice can restore hematopoiesis at higher percentages than mononuclear cells mobilized by Plerixafor (40% vs. 20%, respectively). Further, a secondary transplant rescued a separate group of irradiated mice from death, proving definitive evidence of hematopoietic reconstitution after hematopoietic stem cells transplantation. Data are presented as mean ± standard deviation. To determine significant differences between the data, one-way ANOVA and the Tukey test were used. CONCLUSIONS Collectively these results show the utility of sodium caseinate as a mobilizer of hematopoietic stem cells and its potential clinical application in transplantation settings.

Peripheral Nerve Blocks Causing Increased Risk for Fall and Difficulty in Ambulation for the Hip and Knee Joint Replacement Patient.

PubMed

Crumley Aybar, Bonnie L; Gillespie, Michael J; Gipson, Sean F; Mullaney, Caitlin E; Tommasino-Storz, Melissa

2016-12-01

A systematic review of the literature was completed by the Evidence-Based Practice Group for the Patient population, Intervention/Issue, Comparison Intervention, Outcomes, Timing (PICOT) question: "Does the use of a peripheral nerve block increase the risk for falls and difficulty ambulation in patients after lower extremity surgery through postoperative day 2?" A search of multiple databases using specified key terms resulted in 258 articles for total knee arthroplasty or total hip arthroplasty. These were reduced to 13 with exclusion criteria and became primary evidence. Numbers Needed to Harm and Numbers Needed to Treat (NNT) were calculated. Numbers Needed to Harm supported the PICOT question. Further research of postoperative falls and nursing interventions to reduce or prevent falls is suggested before creation of a Clinical Practice Guideline. Copyright © 2016 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Secondary stroke prevention: from guidelines to clinical practice.

PubMed

Graham, Glenn D

2008-10-01

Stroke remains a leading cause of mortality and is associated with substantial morbidity in the United States. The majority of strokes are of ischemic origin, with an atherothrombotic trigger, and the clinical manifestation of atherothrombosis depends on the affected vascular site. The systemic nature of atherosclerosis means that stroke patients are at increased risk of ischemic events in several vascular beds, including cerebral, coronary and peripheral sites. Because stroke patients are at heightened risk of more ischemic events, secondary prevention is an important therapeutic goal. Recently, the American Heart Association and its division, the American Stroke Association, released new evidence-based guidelines for secondary stroke prevention in patients with ischemic stroke or transient ischemic attack. The new guidelines emphasize an individualized, patient-oriented approach to treatment based on clinical evidence. Evidence-based recommendations are set forth for the management of risk factors, including hypertension, dyslipidemia and diabetes, through lifestyle modifications and pharmacological interventions. The purpose of this paper is to review the topic of stroke prevention in light of current guidelines and clinical implementation patterns for primary care physicians, and to discuss new and emerging clinical evidence, with a focus on antiplatelet treatment.

Lower Limb Arteriovenous Communications in Diabetes Mellitus: A Potential Reason for Aggravation of Ischemic Symptoms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamady, Mohamad S.; Yu, Dominic F.; Sayer, Gabriel L.

2006-10-15

The aim of this study was to assess the prevalence and to evaluate the clinical associations of arteriovenous communications in patients with diabetes mellitus (DM) and lower limb peripheral arterial ischemia. Peripheral arteriography of DM patients from an eight-year period (1993-2000) was evaluated retrospectively by two observers. The presence of arteriovenous communications, defined as occurring without evidence of a preceding precipitating event, and the distribution and severity of the vascular disease were evaluated. The type (non-insulin-dependent DM or insulin-dependent DM) and the duration of the DM, the presenting symptoms, and the presence of a peripheral neuropathy were documented by amore » review of the clinical records. A total of 348 arteriography studies in 285 DM patients were evaluated (duration of DM: median, 16 years; range, 7-42 years); an arteriovenous communication was present in 14/285 patients (4.9%), 9 male and 5 female (median age, 71 years; range, 17-84 years). Symptoms were those of a peripheral leg ulcer (n = 11), claudication (n = 3), and gangrene (n = 1), with symptoms ipsilateral to the side of the arteriovenous communication in 13/14 patients. The sites of the arteriovenous communications were infra popliteal (n = 7), popliteal (n = 3), superficial femoral artery (n = 3), and common femoral artery (n = 1). Features of a peripheral neuropathy were found in 12/14 and ipsilateral to the side of the communication in 11/12. Arteriovenous communications in the peripheral femoral arterial system of patients with DM is an uncommon finding. Although not proven in the current study, arteriovenous communications might be associated with more severe symptoms than that attributable to the underlying vascular disease alone.« less

Management of residual mucogingival defect resulting from the excision of recurrent peripheral ossifying fibroma by periodontal plastic surgical procedure

PubMed Central

Salaria, Sanjeev Kumar; Gupta, Neha; Bhatia, Vineet; Nayar, Amit

2015-01-01

Peripheral ossifying fibroma (POF) is a local gingival reactive lesion, thought to be originating from the superficial periodontal ligament. It is found most often in the anterior maxilla with predilection for females and high recurrence rate. Clinically, the lesion is observed in gingiva or interdental papilla and manifested either as sessile or pedunculated mass which may appear ulcerated or erythematous or exhibit no color difference from the adjacent healthy gingival tissue. The present case report describes the diagnosis, treatment of POF, and immediate management of residual functional and cosmetic mucogingival defect which originated as a sequel of excisional biopsy of recurrent POF by utilizing modification of Grupe and Warren technique (modified laterally displaced flap). Clinical healing was uneventful at 2 weeks, and excellent coverage of residual mucogingival defect without any evidence of recession and or recurrence of POF was observed at surgical site 9 months postoperatively. PMID:26604587

Management of residual mucogingival defect resulting from the excision of recurrent peripheral ossifying fibroma by periodontal plastic surgical procedure.

PubMed

Salaria, Sanjeev Kumar; Gupta, Neha; Bhatia, Vineet; Nayar, Amit

2015-09-01

Peripheral ossifying fibroma (POF) is a local gingival reactive lesion, thought to be originating from the superficial periodontal ligament. It is found most often in the anterior maxilla with predilection for females and high recurrence rate. Clinically, the lesion is observed in gingiva or interdental papilla and manifested either as sessile or pedunculated mass which may appear ulcerated or erythematous or exhibit no color difference from the adjacent healthy gingival tissue. The present case report describes the diagnosis, treatment of POF, and immediate management of residual functional and cosmetic mucogingival defect which originated as a sequel of excisional biopsy of recurrent POF by utilizing modification of Grupe and Warren technique (modified laterally displaced flap). Clinical healing was uneventful at 2 weeks, and excellent coverage of residual mucogingival defect without any evidence of recession and or recurrence of POF was observed at surgical site 9 months postoperatively.

Vitamin B-12 status and neurologic function in older people: a cross-sectional analysis of baseline trial data from the Older People and Enhanced Neurological Function (OPEN) study.

PubMed

Miles, Lisa M; Allen, Elizabeth; Mills, Kerry; Clarke, Robert; Uauy, Ricardo; Dangour, Alan D

2016-09-01

Aging is associated with a progressive decline in vitamin B-12 status. Overt vitamin B-12 deficiency causes neurologic disturbances in peripheral and central motor and sensory systems, but the public health impact for neurologic disease of moderately low vitamin B-12 status in older people is unclear. Evidence from observational studies is limited by heterogeneity in the definition of vitamin B-12 status and imprecise measures of nerve function. We aimed to determine whether vitamin B-12 status is associated with electrophysiologic indexes of peripheral or central neurologic function in asymptomatic older people with moderately low vitamin B-12 status. We used a cross-sectional analysis of baseline data from the Older People and Enhanced Neurological Function study conducted in Southeast England. This trial investigated the effectiveness of vitamin B-12 supplementation on electrophysiologic indexes of neurologic function in asymptomatic older people (mean age: 80 y) with moderately low vitamin B-12 status (serum vitamin B-12 concentrations ≥107 and <210 pmol/L without anemia, n = 201). Vitamin B-12 status was assessed with the use of total vitamin B-12, holotranscobalamin, and a composite indicator of vitamin B-12 status (cB-12). Electrophysiologic measures of sensory and motor components of peripheral and central nerve function were assessed in all participants by a single observer. In multivariate models, there was no evidence of an association of vitamin B-12, holotranscobalamin, or cB-12 with any nerve conduction outcome. There was also no evidence of an association of vitamin B-12 status with clinical markers of neurologic function. This secondary analysis of high-quality trial data did not show any association of any measure of vitamin B-12 status with either peripheral or central neurologic function or any clinical markers of neurologic function in older people with moderately low vitamin B-12 status. The results of this study are unlikely to be generalizable to a less healthy older population with more severe vitamin B-12 deficiency. This trial was registered at www.controlled-trials.com as ISRCTN54195799. © 2016 American Society for Nutrition.

Nerve and muscle involvement in mitochondrial disorders: an electrophysiological study.

PubMed

Mancuso, Michelangelo; Piazza, Selina; Volpi, Leda; Orsucci, Daniele; Calsolaro, Valeria; Caldarazzo Ienco, Elena; Carlesi, Cecilia; Rocchi, Anna; Petrozzi, Lucia; Calabrese, Rosanna; Siciliano, Gabriele

2012-04-01

Involvement of the peripheral nervous system in mitochondrial disorders (MD) has been previously reported. However, the exact prevalence of peripheral neuropathy and/or myopathy in MD is still unclear. In order to evaluate the prevalence of neuropathy and myopathy in MD, we performed sensory and motor nerve conduction studies (NCS) and concentric needle electromyography (EMG) in 44 unselected MD patients. NCS were abnormal in 36.4% of cases, and were consistent with a sensori-motor axonal multineuropathy (multifocal neuropathy), mainly affecting the lower limbs. EMG evidence of myopathy was present in 54.5% of patients, again mainly affecting the lower limbs. Nerve and muscle involvement was frequently subclinical. Peripheral nerve and muscle involvement is common in MD patients. Our study supports the variability of the clinical expression of MD. Further studies are needed to better understand the molecular basis underlying the phenotypic variability among MD patients.

A Structured Review of Antithrombotic Therapy in Peripheral Artery Disease With a Focus on Revascularization: A TASC (InterSociety Consensus for the Management of Peripheral Artery Disease) Initiative.

PubMed

Hess, Connie N; Norgren, Lars; Ansel, Gary M; Capell, Warren H; Fletcher, John P; Fowkes, F Gerry R; Gottsäter, Anders; Hitos, Kerry; Jaff, Michael R; Nordanstig, Joakim; Hiatt, William R

2017-06-20

Peripheral artery disease affects >200 million people worldwide and is associated with significant limb and cardiovascular morbidity and mortality. Limb revascularization is recommended to improve function and quality of life for symptomatic patients with peripheral artery disease with intermittent claudication who have not responded to medical treatment. For patients with critical limb ischemia, the goals of revascularization are to relieve pain, help wound healing, and prevent limb loss. The baseline risk of cardiovascular and limb-related events demonstrated among patients with stable peripheral artery disease is elevated after revascularization and related to atherothrombosis and restenosis. Both of these processes involve platelet activation and the coagulation cascade, forming the basis for the use of antiplatelet and anticoagulant therapies to optimize procedural success and reduce postprocedural cardiovascular risk. Unfortunately, few high-quality, randomized data to support use of these therapies after peripheral artery disease revascularization exist, and much of the rationale for the use of antiplatelet agents after endovascular peripheral revascularization is extrapolated from percutaneous coronary intervention literature. Consequently, guideline recommendations for antithrombotic therapy after lower limb revascularization are inconsistent and not always evidence-based. In this context, the purpose of this structured review is to assess the available randomized data for antithrombotic therapy after peripheral arterial revascularization, with a focus on clinical trial design issues that may affect interpretation of study results, and highlight areas that require further investigation. © 2017 American Heart Association, Inc.

Interventional management of neuropathic pain: NeuPSIG recommendations

PubMed Central

Dworkin, Robert H.; O’Connor, Alec B.; Kent, Joel; Mackey, Sean C.; Raja, Srinivasa N.; Stacey, Brett R.; Levy, Robert M.; Backonja, Miroslav; Baron, Ralf; Harke, Henning; Loeser, John D.; Treede, Rolf-Detlef; Turk, Dennis C.; Wells, Christopher D.

2015-01-01

Neuropathic pain (NP) is often refractory to pharmacologic and non-interventional treatment. On behalf of the International Association for the Study of Pain Neuropathic Pain Special Interest Group (NeuPSIG), the authors evaluated systematic reviews, clinical trials, and existing guidelines for the interventional management of NP. Evidence is summarized and presented for neural blockade, spinal cord stimulation (SCS), intrathecal medication, and neurosurgical interventions in patients with the following peripheral and central NP conditions: herpes zoster and postherpetic neuralgia (PHN); painful diabetic and other peripheral neuropathies; spinal cord injury NP; central post-stroke pain; radiculopathy and failed back surgery syndrome (FBSS); complex regional pain syndrome (CRPS); and trigeminal neuralgia and neuropathy. Due to the paucity of high-quality clinical trials, no strong recommendations can be made. Four weak recommendations based on the amount and consistency of evidence, including degree of efficacy and safety, are: (1) epidural injections for herpes zoster; (2) steroid injections for radiculopathy; (3) SCS for FBSS; and (4) SCS for CRPS type 1. Based on the available data, we recommend not to use sympathetic blocks for PHN nor RF lesions for radiculopathy. No other conclusive recommendations can be made due to the poor quality of available of data. Whenever possible, these interventions should either be part of randomized clinical trials or documented in pain registries. Priorities for future research include randomized clinical trials; long-term studies; and head-to-head comparisons among different interventional and non-interventional treatments. PMID:23748119

Intratemporal facial nerve ultrastructure in patients with idiopathic facial paralysis: viral infection evidence study.

PubMed

Florez, Rosangela Aló Maluza; Lang, Raquel; Veridiano, Adriano Mora; Zanini, Renato de Oliveira; Calió, Pedro Luiz; Simões, Ricardo Dos Santos; Testa, José Ricardo Gurgel

2010-01-01

The etiology of idiopathic peripheral facial palsy (IPFP) is still uncertain; however, some authors suggest the possibility of a viral infection. to analyze the ultrastructure of the facial nerve seeking viral evidences that might provide etiological data. We studied 20 patients with peripheral facial palsy (PFP), with moderate to severe FP, of both genders, between 18-60 years of age, from the Clinic of Facial Nerve Disorders. The patients were broken down into two groups - Study: eleven patients with IPFP and Control: nine patients with trauma or tumor-related PFP. The fragments were obtained from the facial nerve sheath or from fragments of its stumps - which would be discarded or sent to pathology exam during the facial nerve repair surgery. The removed tissue was fixed in 2% glutaraldehyde, and studied under Electronic Transmission Microscopy. In the study group we observed an intense repair cellular activity by increased collagen fibers, fibroblasts containing developed organelles, free of viral particles. In the control group this repair activity was not evident, but no viral particles were observed. There were no viral particles, and there were evidences of intense activity of repair or viral infection.

Ethnic differences in the +405 and -460 vascular endothelial growth factor polymorphisms and peripheral neuropathy in patients with diabetes residing in a North London, community in the United Kingdom.

PubMed

Zitouni, Karima; Tinworth, Lorna; Earle, Kenneth Anthony

2017-06-29

There are marked ethnic differences in the susceptibility to the long-term diabetic vascular complications including sensory neuropathy. The vascular endothelial growth factor (VEGF) +405 (C/G) and -460 (T/C) polymorphisms are associated with retinopathy and possibly with nephropathy, however no information is available on their relationship with peripheral neuropathy. Therefore, we examined the prevalence of these VEGF genotypes in a multi-ethnic cohort of patients with diabetes and their relationship with evident peripheral diabetic neuropathy. In the current investigation, we studied 313 patients with diabetes mellitus of African-Caribbean, Indo-Asian and Caucasian ethnic origin residing in an inner-city community in London, United Kingdom attending a single secondary care centre. Genotyping was performed for the VEGF +405 and VEGF -460 polymorphisms using a pyrosequencing technique. Forty-nine patients (15.6%) had clinical evidence of peripheral neuropathy. Compared to Caucasian patients, African-Caribbean and Indo-Asian patients had lower incidence of neuropathy (24.6%, 14.28%, 6.7%, respectively; P = 0.04). The frequency of the VEGF +405 GG genotype was more common in Indo-Asian patients compared to African-Caribbean and Caucasian patients (67.5%, 45.3%, 38.4%, respectively; p ≤ 0.02). The G allele was more common in patients with type 2 diabetes of Indo-Asian origin compared to African-Caribbean and Caucasian origin (p ≤ 0.02). There was no difference between the ethnic groups in VEGF -460 genotypes. The distributions of the VEGF +405 and VEGF -460 genotypes were similar between the diabetic patients with and without neuropathy. In this cohort of patients, VEGF +405 and VEGF -460 polymorphisms were not associated with evident diabetic peripheral neuropathy, however an association was found between VEGF +405 genotypes and Indo-Asian which might have relevance to their lower rates of ulceration and amputation. This finding highlights the need for further investigation of any possible relationship between VEGF genotype, circulating VEGF concentrations and differential vulnerability to peripheral neuropathy amongst diabetic patients of different ethnic backgrounds.

Behavioural conditioning of immune functions: how the central nervous system controls peripheral immune responses by evoking associative learning processes.

PubMed

Riether, Carsten; Doenlen, Raphaël; Pacheco-López, Gustavo; Niemi, Maj-Britt; Engler, Andrea; Engler, Harald; Schedlowski, Manfred

2008-01-01

During the last 30 years of psychoneuroimmunology research the intense bi-directional communication between the central nervous system (CNS) and the immune system has been demonstrated in studies on the interaction between the nervous-endocrine-immune systems. One of the most intriguing examples of such interaction is the capability of the CNS to associate an immune status with specific environmental stimuli. In this review, we systematically summarize experimental evidence demonstrating the behavioural conditioning of peripheral immune functions. In particular, we focus on the mechanisms underlying the behavioural conditioning process and provide a theoretical framework that indicates the potential feasibility of behaviourally conditioned immune changes in clinical situations.

Sensory re-education after nerve injury of the upper limb: a systematic review.

PubMed

Oud, Tanja; Beelen, Anita; Eijffinger, Elianne; Nollet, Frans

2007-06-01

To systematically review the available evidence for the effectiveness of sensory re-education to improve the sensibility of the hand in patients with a peripheral nerve injury of the upper limb. Studies were identified by an electronic search in the databases MEDLINE, Cumulative Index to Nursing & Allied Health Literature (CINAHL), EMBASE, the Cochrane Library, the Physiotherapy Evidence Database (PEDro), and the database of the Dutch National Institute of Allied Health Professions (Doconline) and by screening the reference lists of relevant articles. Two reviewers selected studies that met the following inclusion criteria: all designs except case reports, adults with impaired sensibility of the hand due to a peripheral nerve injury of the upper limb, and sensibility and functional sensibility as outcome measures. The methodological quality of the included studies was independently assessed by two reviewers. A best-evidence synthesis was performed, based on design, methodological quality and significant findings on outcome measures. Seven studies, with sample sizes ranging from 11 to 49, were included in the systematic review and appraised for content. Five of these studies were of poor methodological quality. One uncontrolled study (N = 1 3 ) was considered to be of sufficient methodological quality, and one randomized controlled trial (N = 49) was of high methodological quality. Best-evidence synthesis showed that there is limited evidence for the effectiveness of sensory re-education, provided by a statistically significant improvement in sensibility found in one high-quality randomized controlled trial. There is a need for further well-defined clinical trials to assess the effectiveness of sensory re-education of patients with impaired sensibility of the hand due to a peripheral nerve injury.

Role of orexins in the central and peripheral regulation of glucose homeostasis: Evidences & mechanisms.

PubMed

Rani, Monika; Kumar, Raghuvansh; Krishan, Pawan

2018-04-01

Orexins (A & B), neuropeptides of hypothalamic origin, act through G-protein coupled receptors, orexin 1 receptor (OX 1 R) and orexin 2 receptor (OX 2 R). The wide projection of orexin neurons in the hypothalamic region allows them to interact with the other neurons and regulate food intake, emotional status, sleep wake cycle and energy metabolism. The autonomic nervous system plays an important regulatory role in the energy metabolism as well as glucose homeostasis. Orexin neurons are also under the control of GABAergic neurons. Emerging preclinical as well as clinical research has reported the role of orexins in the glucose homeostasis since orexins are involved in hypothalamic metabolism circuitry and also rely on sensing peripheral metabolic signals such as gut, adipose derived and pancreatic peptides. Apart from the hypothalamic origin, integration and control in various physiological functions, peripheral origin in wide organs, raises the possibility of use of orexins as a therapeutic biomarker in the management of metabolic disorders. The present review focuses the central as well as peripheral roles of orexins in the glucose homeostasis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Erythrocyte dysplasia in peripheral blood smears from 5 thrombocytopenic dogs treated with vincristine sulfate.

PubMed

Collicutt, Nancy B; Garner, Bridget

2013-12-01

Secondary dyserythropoiesis has been associated with vincristine administration in dogs. Evaluation of bone marrow aspirates for the presence of morphologic abnormalities in the erythroid lineage aids in the diagnosis. However, morphologic features of circulating erythroid precursors in these cases have not been described previously. The purpose of this report was to describe the cytologic features of dyserythropoiesis in peripheral blood and also bone marrow smears in a case series of dogs with immune-mediated thrombocytopenia (IMT) treated with vincristine sulfate. Nineteen dogs receiving vincristine for treatment of IMT were identified by retrospectively searching a computerized medical record system. There were 5 dogs that had dysplastic erythroid precursors in peripheral blood smears within 7 days of vincristine treatment. Two of those 5 dogs also had evidence for erythrodysplasia in modified Wright's-stained bone marrow smears obtained postvincristine administration. Morphologic changes included bizarre or inappropriate mitotic figures, abnormal nuclear configurations (fragmentation, elongation, indentation, and binucleation), atypical nuclear remnants (Howell-Jolly bodies), or nuclear and cytoplasmic asynchrony within the erythroid precursors. A brief review of the literature with discussion of the etiologies for dyserythropoiesis is provided. The dyserythropoiesis was clinically insignificant in all 5 cases and resolved. However, pathologists and clinicians should be aware of these potential findings to prevent misdiagnosis of other conditions. © 2013 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.

Sensory neuropathy may cause central neuronal reorganization but does not respecify perceptual quality or localization of sensation.

PubMed

Ginanneschi, Federica; Mondelli, Mauro; Rossi, Alessandro

2012-10-01

Functional reorganization in the somatosensory network after peripheral nerve lesions has been suspected to modify the clinical expression of symptoms. However, no conclusive evidence exists to support this notion. We addressed this question by investigating the topographic distribution of the subjective sensory report in various chronic human mononeuropathies. We report the clinical results of 86 patients who were diagnosed with meralgia paresthetica, 86 patients with ulnar neuropathy at the elbow, and 203 patients with carpal tunnel syndrome. In the carpal tunnel syndrome group, 10% of the patients exhibited a spread of sensory symptoms beyond the innervation territory of the median nerve. As previously reported, this spread was contingent upon an indirect compressive lesion of the ulnar nerve at the wrist. In all of the patients who were affected with meralgia paresthetica or ulnar neuropathy at the elbow, the peripheral referral of sensation was always within the anatomic distribution of the affected nerve. In human neuropathies, the projected sensory symptoms are restricted to the innervation territories of the affected nerves, with no extraterritorial spread. Thus, the somatosensory localization function remains accurate, despite the central reorganization that presumably occurs after nerve injury. We conclude that reorganization of the sensory connections within the central nervous system after peripheral nerve injury in humans is a clinically silent adaptive phenomenon.

Microbial contamination of autologous peripheral blood stem cell products: incidence, clinical outcome, quality control and management strategies.

PubMed

Cheah, Poh Lin; Ong, Chong Wei; Crispin, Philip

2011-06-01

Microbial screening is part of quality control for autologous peripheral blood stem cell (PBSC) manipulation. The incidence of culture positive products varies widely. The clinical significance of infusing culture positive products is uncertain, with no consensus on the interventions required. Microbial cultures of 606 consecutive autologous PBSC products from 278 patients between 1995 and 2005 were retrospectively analysed to determine the incidence of culture positivity and classified according to likely clinical significance. Clinical outcomes of patients who received culture positive products were reviewed. Using the baseline probability of contamination, a quality control method to detect a systematic source of contamination during product manipulation was developed. Eleven (1.8%) of 606 products were culture positive in eight (2.9%) patients. Ten products yielded coagulase negative Staphylococcus species and one Corynebacterium accolens. One patient had catheter sepsis during collection. Five patients received culture positive products, with prophylactic antibiotics when there was known coagulase negative Staphylococcus species. None had clinical evidence of infection following product infusion. The incidence of culture positive products was comparable to published series. Only skin commensals were isolated. Infusion of skin commensal positive products appears safe with antibiotic prophylaxis. Using local and published experience, clinical and laboratory policies were developed for culture positive products.

Peripheral μ-opioid receptor mediated inhibition of calcium signaling and action potential-evoked calcium fluorescent transients in primary afferent CGRP nociceptive terminals.

PubMed

Baillie, Landon D; Schmidhammer, Helmut; Mulligan, Sean J

2015-06-01

While μ-opioid receptor (MOR) agonists remain the most powerful analgesics for the treatment of severe pain, serious adverse side effects that are secondary to their central nervous system actions pose substantial barriers to therapeutic use. Preclinical and clinical evidence suggest that peripheral MORs play an important role in opioid analgesia, particularly under inflammatory conditions. However, the mechanisms of peripheral MOR signaling in primary afferent pain fibres remain to be established. We have recently introduced a novel ex vivo optical imaging approach that, for the first time, allows the study of physiological functioning within individual peripheral nociceptive fibre free nerve endings in mice. In the present study, we found that MOR activation in selectively identified, primary afferent CGRP nociceptive terminals caused inhibition of N-type Ca(2+) channel signaling and suppression of action potential-evoked Ca(2+) fluorescent transients mediated by 'big conductance' Ca(2+)-activated K(+) channels (BKCa). In the live animal, we showed that the peripherally acting MOR agonist HS-731 produced analgesia and that BKCa channels were the major effectors of the peripheral MOR signaling. We have identified two key molecular transducers of MOR activation that mediate significant inhibition of nociceptive signaling in primary afferent terminals. Understanding the mechanisms of peripheral MOR signaling may promote the development of pathway selective μ-opioid drugs that offer improved therapeutic profiles for achieving potent analgesia while avoiding serious adverse central side effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Investigational opioid antagonists for treating opioid-induced bowel dysfunction.

PubMed

Mozaffari, Shilan; Nikfar, Shekoufeh; Abdollahi, Mohammad

2018-03-01

Opioids have been highlighted for their role in pain relief among cancer and non-cancer patients. Novel agents have been investigated to reduce opioid-induced constipation (OIC) as the main adverse effect that may lead to treatment discontinuation. Development of peripherally acting mu-opioid receptor antagonists (PAMORA) has resulted in a novel approach to preserve the efficacy of pain control along with less OIC. Areas covered: Clinical evidence for investigational PAMORAs was reviewed and clinical trials on investigational agents to reduce OIC were included. TD-1211 is currently being evaluated in Phase II clinical trial. Oxycodone-naltrexone and ADL-5945 went through Phase III clinical trials, but have been discontinued. Expert opinion: There is a substantial need to develop agents with specific pharmacokinetic properties to meet the needs of patients with underlying diseases. Holding the efficacy of a medicine with the highest selectivity on targeted receptors and the least adverse effects is the main approach in upcoming investigations to improve patients' quality of life (QoL). Novel agents to reduce opioid-induced bowel dysfunction (OIBD) that do not reverse peripherally mediated pain analgesia are of great interest. Direct comparison of available agents in this field is lacking in the literature.

Lung penetration and patient adherence considerations in the management of asthma: role of extra-fine formulations

PubMed Central

Scichilone, Nicola; Spatafora, Mario; Battaglia, Salvatore; Arrigo, Rita; Benfante, Alida; Bellia, Vincenzo

2013-01-01

The mainstay of management in asthma is inhalation therapy at the target site, with direct delivery of the aerosolized drug into the airways to treat inflammation and relieve obstruction. Abundant evidence is available to support the concept that inflammatory and functional changes at the level of the most peripheral airways strongly contribute to the complexity and heterogeneous manifestations of asthma. It is now largely accepted that there is a wide range of clinical phenotypes of the disease, characterized primarily by small airways involvement. Thus, an appropriate diagnostic algorithm cannot exclude biological and functional assessment of the peripheral airways. Similarly, achievement of optimal control of the disease and appropriate management of specific phenotypes of asthma should be based on drugs (and delivery options) able to distribute uniformly along the bronchial tree and to reach the most peripheral airways. Products developed with the Modulite® technology platform have been demonstrated to meet these aims. Recent real-life studies have shown clearly that extra-fine fixed-combination inhaled therapy provides better asthma control than non-extra-fine formulations, thus translating the activity of the drugs into greater effectiveness in clinical practice. We suggest that in patients with incomplete asthma control despite good lung function, involvement of the peripheral airways should always be suspected. When this is the case, treatments targeting both the large and small airways should be used to improve asthma control. Above all, it is emphasized that patient adherence with prescribed medications can contribute to clinical success, and clinicians should always be aware of the role played by patients themselves in determining the success or failure of treatment. PMID:23378776

Effect of Vitamin E on Oxaliplatin-induced Peripheral Neuropathy Prevention: A Randomized Controlled Trial.

PubMed

Salehi, Zeinab; Roayaei, Mahnaz

2015-01-01

Peripheral neuropathy is one of the most important limitations of oxaliplatin base regimen, which is the standard for the treatment of colorectal cancer. Evidence has shown that Vitamin E may be protective in chemotherapy-induced peripheral neuropathy. The aim of this study is to evaluate the effect of Vitamin E administration on prevention of oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer. This was a prospective randomized, controlled clinical trial. Patients with colorectal cancer and scheduled to receive oxaliplatin-based regimens were enrolled in this study. Enrolled patients were randomized into two groups. The first group received Vitamin E at a dose of 400 mg daily and the second group observed, until after the sixth course of the oxaliplatin regimen. For oxaliplatin-induced peripheral neuropathy assessment, we used the symptom experience diary questionnaire that completed at baseline and after the sixth course of chemotherapy. Only patients with a score of zero at baseline were eligible for this study. Thirty-two patients were randomized to the Vitamin E group and 33 to the control group. There was no difference in the mean peripheral neuropathy score changes (after - before) between two groups, after sixth course of the oxaliplatin base regimen (mean difference [after - before] of Vitamin E group = 6.37 ± 2.85, control group = 6.57 ± 2.94; P = 0.78). Peripheral neuropathy scores were significantly increased after intervention compared with a base line in each group (P < 0.001). The results from this current trial demonstrate a lack of benefit for Vitamin E in preventing oxaliplatin-induced peripheral neuropathy.

Peripheral Neuropathy – Clinical and Electrophysiological Considerations

PubMed Central

Chung, Tae; Prasad, Kalpana; Lloyd, Thomas E.

2013-01-01

This article is a primer on the pathophysiology and clinical evaluation of peripheral neuropathy for the radiologist. Magnetic resonance neurography (MRN) has utility in the diagnosis of many focal peripheral nerve lesions. When combined with history, examination, electrophysiology, and laboratory data, future advancements in high-field MRN may play an increasingly important role in the evaluation of patients with peripheral neuropathy. PMID:24210312

Clinical effectiveness of low-level laser treatment on peripheral somatosensory neuropathy.

PubMed

Fallah, Alireza; Mirzaei, Alireza; Gutknecht, Norbert; Demneh, Amir Saberi

2017-04-01

Peripheral sensory neuropathy treatment is one of the common treatment problems and causes morbidity and mortality in people suffering from that. Although treatment depends on the underlying cause of the condition, nevertheless, in some cases, there is no cure for it, and it requires palliative and symptomatic treatment. In laboratory studies, low-level laser has been effective in the nerves protection and restoration. The aim of this article is to investigate the clinical efficacy of low-level laser on improvement of the peripheral somatosensory neuropathy. Search in the articles published up to 30 October 2015 (full text and abstracts) in databases PubMed (Medline), Cochrane library, Physiotherapy Evidence Database was performed. The studies of low-level laser trials on patients with peripheral neuropathy were carried out and evaluated in terms of the exclusion criteria. There are 35 articles among which 10 articles had the intended and required criteria. 1, 3, and 6 articles study the patients with diabetes, neuropathy caused by trauma, and carpal tunnel syndrome, respectively. In six studies, laser led to a reduction in sensory impairment and improvement of the physiological function of the sensory nerves. In these articles, lasers (Diode, GaAlAs, He-Ne) had wavelength range 660-860 nm, radiation power 20-250 mW, energy density 0.45-70 J/cm 2 . The intervention sessions range was 6-21 times and patient follow-up was 0-6 months. According to the results of these studies, low-level laser therapy can improve sensory function in patients with peripheral somatosensory neuropathy, although little research have not been done, laser treatment regimens are varied and do not recommend a specific treatment protocol. It seems it requires more research to sum up better, particularly in relation to diabetes.

Threshold dose for peripheral neuropathy following intraoperative radiotherapy (IORT) in a large animal model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kinsella, T.J.; DeLuca, A.M.; Barnes, M.

1991-04-01

Radiation injury to peripheral nerve is a dose-limiting toxicity in the clinical application of intraoperative radiotherapy, particularly for pelvic and retroperitoneal tumors. Intraoperative radiotherapy-related peripheral neuropathy in humans receiving doses of 20-25 Gy is manifested as a mixed motor-sensory deficit beginning 6-9 months following treatment. In a previous experimental study of intraoperative radiotherapy-related neuropathy of the lumbro-sacral plexus, an approximate inverse linear relationship was reported between the intraoperative dose (20-75 Gy range) and the time to onset of hind limb paresis (1-12 mos following intraoperative radiotherapy). The principal histological lesion in irradiated nerve was loss of large nerve fibers andmore » perineural fibrosis without significant vascular injury. Similar histological changes in irradiated nerves were found in humans. To assess peripheral nerve injury to lower doses of intraoperative radiotherapy in this same large animal model, groups of four adult American Foxhounds received doses of 10, 15, or 20 Gy to the right lumbro-sacral plexus and sciatic nerve using 9 MeV electrons. The left lumbro-sacral plexus and sciatic nerve were excluded from the intraoperative field to allow each animal to serve as its own control. Following treatment, a complete neurological exam, electromyogram, and nerve conduction studies were performed monthly for 1 year. Monthly neurological exams were performed in years 2 and 3 whereas electromyogram and nerve conduction studies were performed every 3 months during this follow-up period. With follow-up of greater than or equal to 42 months, no dog receiving 10 or 15 Gy IORT shows any clinical or laboratory evidence of peripheral nerve injury. However, all four dogs receiving 20 Gy developed right hind limb paresis at 8, 9, 9, and 12 mos following intraoperative radiotherapy.« less

[Clinical studies in peripheral arterial occlusive disease: update from the aspects of a meta-narrative review].

PubMed

Melzer, Jörg; Saller, Reinhard

2013-01-01

Atherosclerosis is a systemic disease. Its association with the metabolic syndrome requires a multimodal therapy setting, to alleviate symptoms and for primary and secondary prevention. In the planning of the therapy, information about evidence of the interventions and a rationale for reasonable combinations are important. For compiling a meta-narrative review (MNR) on the evidence of complementary and conventional pharmaco-therapy in peripheral arterial occlusive disease (PAOD), the literature was searched for meta-analyses of randomized controlled trials (RCTs). These were evaluated taking into account network-pharmacological aspects and research parameters. 4 suitable meta-analyses were found. In comparison to placebo, treatments with verum showed a significant improvement of the maximum walking distance of 63.5 m (95% confidence interval (CI) 27.11-99.91 m; Padma 28, Tibetan Formula), 41.3 m (95% CI -7.1-89.7 m; cilostazol, phosphodiesterase IIl inhibitor), 43.8 m (95% CI 14.1-73.6 m; pentoxifylline, rheological drug), and 71.2 m (95% CI 13.3-129.0 m; naftidrofuryl, rheological drug). Only for Padma 28, clinical relevance, defined as an increase of the maximum walking distance by >100 m, was analyzed and reached by 18.2% of the verum and 2.1% of the placebo patients (odds ratio 10; 95% CI 3.03-33.33). 1 conventional and 1 complementary drug additionally showed to have significant pleiotropic effects (Padma 28 and cilostazol (e.g. reduction of triglycerides)). According to meta-analytic evidence, naftidrofuryl and Padma 28 show clinically relevant efficacy for the treatment of early stages of PAOD. The extent to which the theoretically possible combination of different drugs contributes to improve the systemic disease under a network-pharmacological rationale remains to be shown in a multi-armed RCT.

Integrative Therapies During and After Breast Cancer Treatment: ASCO Endorsement of the SIO Clinical Practice Guideline.

PubMed

Lyman, Gary H; Greenlee, Heather; Bohlke, Kari; Bao, Ting; DeMichele, Angela M; Deng, Gary E; Fouladbakhsh, Judith M; Gil, Brigitte; Hershman, Dawn L; Mansfield, Sami; Mussallem, Dawn M; Mustian, Karen M; Price, Erin; Rafte, Susan; Cohen, Lorenzo

2018-06-11

Purpose The Society for Integrative Oncology (SIO) produced an evidence-based guideline on use of integrative therapies during and after breast cancer treatment that was determined to be relevant to the American Society of Clinical Oncology (ASCO) membership. ASCO considered the guideline for endorsement. Methods The SIO guideline addressed the use of integrative therapies for the management of symptoms and adverse effects, such as anxiety and stress, mood disorders, fatigue, quality of life, chemotherapy-induced nausea and vomiting, lymphedema, chemotherapy-induced peripheral neuropathy, pain, and sleep disturbance. Interventions of interest included mind and body practices, natural products, and lifestyle modifications. SIO systematic reviews focused on randomized controlled trials that were published from 1990 through 2015. The SIO guideline was reviewed by ASCO content experts for clinical accuracy and by ASCO methodologists for developmental rigor. On favorable review, an ASCO Expert Panel was convened to review the guideline contents and recommendations. Results The ASCO Expert Panel determined that the recommendations in the SIO guideline-published in 2017-are clear, thorough, and based on the most relevant scientific evidence. ASCO endorsed the guideline with a few added discussion points. Recommendations Key recommendations include the following: Music therapy, meditation, stress management, and yoga are recommended for anxiety/stress reduction. Meditation, relaxation, yoga, massage, and music therapy are recommended for depression/mood disorders. Meditation and yoga are recommended to improve quality of life. Acupressure and acupuncture are recommended for reducing chemotherapy-induced nausea and vomiting. Acetyl-l-carnitine is not recommended to prevent chemotherapy-induced peripheral neuropathy because of a possibility of harm. No strong evidence supports the use of ingested dietary supplements to manage breast cancer treatment-related adverse effects. Additional information is available at: www.asco.org/supportive-care-guidelines .

Burning mouth syndrome.

PubMed

Jääskeläinen, Satu K; Woda, Alain

2017-06-01

Objective To review the clinical entity of primary burning mouth syndrome (BMS), its pathophysiological mechanisms, accurate new diagnostic methods and evidence-based treatment options, and to describe novel lines for future research regarding aetiology, pathophysiology, and new therapeutic strategies. Description Primary BMS is a chronic neuropathic intraoral pain condition that despite typical symptoms lacks clear clinical signs of neuropathic involvement. With advanced diagnostic methods, such as quantitative sensory testing of small somatosensory and taste afferents, neurophysiological recordings of the trigeminal system, and peripheral nerve blocks, most BMS patients can be classified into the peripheral or central type of neuropathic pain. These two types differ regarding pathophysiological mechanisms, efficacy of available treatments, and psychiatric comorbidity. The two types may overlap in individual patients. BMS is most frequent in postmenopausal women, with general population prevalence of around 1%. Treatment of BMS is difficult; best evidence exists for efficacy of topical and systemic clonazepam. Hormonal substitution, dopaminergic medications, and therapeutic non-invasive neuromodulation may provide efficient mechanism-based treatments for BMS in the future. Conclusion We present a novel comprehensive hypothesis of primary BMS, gathering the hormonal, neuropathic, and genetic factors presumably required in the genesis of the condition. This will aid in future research on pathophysiology and risk factors of BMS, and boost treatment trials taking into account individual mechanism profiles and subgroup-clusters.

Pes cavus and hereditary neuropathies: when a relationship should be suspected.

PubMed

Piazza, S; Ricci, G; Caldarazzo Ienco, E; Carlesi, C; Volpi, L; Siciliano, G; Mancuso, M

2010-12-01

The hereditary peripheral neuropathies are a clinically and genetically heterogeneous group of diseases of the peripheral nervous system. Foot deformities, including the common pes cavus, but also hammer toes and twisting of the ankle, are frequently present in patients with hereditary peripheral neuropathy, and often represent one of the first signs of the disease. Pes cavus in hereditary peripheral neuropathies is caused by imbalance between the intrinsic muscles of the foot and the muscles of the leg. Accurate clinical evaluation in patients with pes cavus is necessary to exclude or confirm the presence of peripheral neuropathy. Hereditary peripheral neuropathies should be suspected in those cases with bilateral foot deformities, in the presence of family history for pes cavus and/or gait impairment, and in the presence of neurological symptoms or signs, such as distal muscle hypotrophy of limbs. Herein, we review the hereditary peripheral neuropathies in which pes cavus plays a key role as a "spy sign," discussing the clinical and molecular features of these disorders to highlight the importance of pes cavus as a helpful clinical sign in these rare diseases.

Pharmacology, toxicology, and clinical use of new long acting local anesthetics, ropivacaine and levobupivacaine.

PubMed

Leone, Stefania; Di Cianni, Simone; Casati, Andrea; Fanelli, Guido

2008-08-01

Levobupivacaine and ropivacaine, two new long-acting local anesthetics, have been developed as an alternative to bupivacaine, after the evidence of its severe toxicity. Both of these agents are pure left-isomers and, due to their three-dimensional structure, seem to have less toxic effects on the central nervous system and on the cardiovascular system. Many clinical studies have investigated their toxicology and clinical profiles: theoretically and experimentally, some differences have been observed, but the effects of these properties on clinical practice have not been shown. By examining randomised, controlled trials that have compared these three local agents, this review supports the evidence that both levobupivacaine and ropivacaine have a clinical profile similar to that of racemic bupivacaine, and that the minimal differences reported between the three anesthetics are mainly related to the slightly different anesthetic potency, with racemic bupivacaine > levobupivacaine > ropivacaine. However, the reduced toxic potential of the two pure left-isomers suggests their use in the clinical situations in which the risk of systemic toxicity related to either overdosing or unintended intravascular injection is high, such as during epidural or peripheral nerve blocks.

Pain Processing and Vegetative Dysfunction in Fibromyalgia: A Study by Sympathetic Skin Response and Laser Evoked Potentials

PubMed Central

Ricci, Katia; Libro, Giuseppe; Vecchio, Eleonora; Delussi, Marianna; Montemurno, Anna; Iannone, Florenzo

2017-01-01

Background A dysfunction of pain processing at central and peripheral levels was reported in fibromyalgia (FM). We aimed to correlate laser evoked potentials (LEPs), Sympathetic Skin Response (SSR), and clinical features in FM patients. Methods Fifty FM patients and 30 age-matched controls underwent LEPs and SSR by the right hand and foot. The clinical evaluation included FM disability (FIQ) and severity scores (WPI), anxiety (SAS) and depression (SDS) scales, and questionnaires for neuropathic pain (DN4). Results The LEP P2 latency and amplitude and the SSR latency were increased in FM group. This latter feature was more evident in anxious patients. The LEPs habituation was reduced in FM patients and correlated to pain severity scores. In a significant number of patients (32%) with higher DN4 and FIQ scores, SSR or LEP responses were absent. Conclusions LEPs and SSR might contribute to clarifying the peripheral and central nervous system involvement in FM patients. PMID:29093972

Pain Processing and Vegetative Dysfunction in Fibromyalgia: A Study by Sympathetic Skin Response and Laser Evoked Potentials.

PubMed

de Tommaso, Marina; Ricci, Katia; Libro, Giuseppe; Vecchio, Eleonora; Delussi, Marianna; Montemurno, Anna; Lopalco, Giuseppe; Iannone, Florenzo

2017-01-01

A dysfunction of pain processing at central and peripheral levels was reported in fibromyalgia (FM). We aimed to correlate laser evoked potentials (LEPs), Sympathetic Skin Response (SSR), and clinical features in FM patients. Fifty FM patients and 30 age-matched controls underwent LEPs and SSR by the right hand and foot. The clinical evaluation included FM disability (FIQ) and severity scores (WPI), anxiety (SAS) and depression (SDS) scales, and questionnaires for neuropathic pain (DN4). The LEP P2 latency and amplitude and the SSR latency were increased in FM group. This latter feature was more evident in anxious patients. The LEPs habituation was reduced in FM patients and correlated to pain severity scores. In a significant number of patients (32%) with higher DN4 and FIQ scores, SSR or LEP responses were absent. LEPs and SSR might contribute to clarifying the peripheral and central nervous system involvement in FM patients.

[The ISP (Safe Insertion of PICCs) protocol: a bundle of 8 recommendations to minimize the complications related to the peripherally inserted central venous catheters (PICC)].

PubMed

Emoli, Alessandro; Cappuccio, Serena; Marche, Bruno; Musarò, Andrea; Scoppettuolo, Giancarlo; Pittiruti, Mauro

2014-01-01

The ISP (Safe Insertion of PICCs) protocol: a bundle of 8 recommendations to minimize the complications related to the peripherally inserted central venous catheters (PICC). The insertion of a peripherally inserted central venous catheter (PICC) is not without risks. The Italian Group for the Study of Long-Term Central Venous Access Devices (GAVeCeLT) has developed a protocol (SIP: Safe Implantation of PICCs) with the aim of minimizing the risks which may be associated with the placement of PICCs. The protocol is based on recommendations available in the literature and on the main clinical practice guidelines. The SIP protocol, a bundle of evidence-based recommendations, it is is easy to use, inexpensive, and cost-effective. If routinely used and carefully inplemented, it greatly reduces complications such as failure of venipuncture, accidental arterial puncture, damage of median nerve, infection and catheter related venous thrombosis.

Vestibular Rehabilitation for Peripheral Vestibular Hypofunction: An Evidence-Based Clinical Practice Guideline

PubMed Central

Herdman, Susan J.; Whitney, Susan L.; Cass, Stephen P.; Clendaniel, Richard A.; Fife, Terry D.; Furman, Joseph M.; Getchius, Thomas S. D.; Goebel, Joel A.; Shepard, Neil T.; Woodhouse, Sheelah N.

2016-01-01

Background: Uncompensated vestibular hypofunction results in postural instability, visual blurring with head movement, and subjective complaints of dizziness and/or imbalance. We sought to answer the question, “Is vestibular exercise effective at enhancing recovery of function in people with peripheral (unilateral or bilateral) vestibular hypofunction?” Methods: A systematic review of the literature was performed in 5 databases published after 1985 and 5 additional sources for relevant publications were searched. Article types included meta-analyses, systematic reviews, randomized controlled trials, cohort studies, case control series, and case series for human subjects, published in English. One hundred thirty-five articles were identified as relevant to this clinical practice guideline. Results/Discussion: Based on strong evidence and a preponderance of benefit over harm, clinicians should offer vestibular rehabilitation to persons with unilateral and bilateral vestibular hypofunction with impairments and functional limitations related to the vestibular deficit. Based on strong evidence and a preponderance of harm over benefit, clinicians should not include voluntary saccadic or smooth-pursuit eye movements in isolation (ie, without head movement) as specific exercises for gaze stability. Based on moderate evidence, clinicians may offer specific exercise techniques to target identified impairments or functional limitations. Based on moderate evidence and in consideration of patient preference, clinicians may provide supervised vestibular rehabilitation. Based on expert opinion extrapolated from the evidence, clinicians may prescribe a minimum of 3 times per day for the performance of gaze stability exercises as 1 component of a home exercise program. Based on expert opinion extrapolated from the evidence (range of supervised visits: 2-38 weeks, mean = 10 weeks), clinicians may consider providing adequate supervised vestibular rehabilitation sessions for the patient to understand the goals of the program and how to manage and progress themselves independently. As a general guide, persons without significant comorbidities that affect mobility and with acute or subacute unilateral vestibular hypofunction may need once a week supervised sessions for 2 to 3 weeks; persons with chronic unilateral vestibular hypofunction may need once a week sessions for 4 to 6 weeks; and persons with bilateral vestibular hypofunction may need once a week sessions for 8 to 12 weeks. In addition to supervised sessions, patients are provided a daily home exercise program. Disclaimer: These recommendations are intended as a guide for physical therapists and clinicians to optimize rehabilitation outcomes for persons with peripheral vestibular hypofunction undergoing vestibular rehabilitation. Video Abstract available for more insights from the author (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A124). PMID:26913496

Guidelines in the management of diabetic nerve pain: clinical utility of pregabalin

PubMed Central

Vinik, Aaron I; Casellini, Carolina M

2013-01-01

Diabetic peripheral neuropathy is a common complication of diabetes. It presents as a variety of syndromes for which there is no universally accepted unique classification. Sensorimotor polyneuropathy is the most common type, affecting about 30% of diabetic patients in hospital care and 25% of those in the community. Pain is the reason for 40% of patient visits in a primary care setting, and about 20% of these have had pain for greater than 6 months. Chronic pain may be nociceptive, which occurs as a result of disease or damage to tissue with no abnormality in the nervous system. In contrast, neuropathic pain is defined as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system.” Persistent neuropathic pain interferes significantly with quality of life, impairing sleep and recreation; it also significantly impacts emotional well-being, and is associated with depression, anxiety, and noncompliance with treatment. Painful diabetic peripheral neuropathy is a difficult-to-manage clinical problem, and patients with this condition are more apt to seek medical attention than those with other types of diabetic neuropathy. Early recognition of psychological problems is critical to the management of pain, and physicians need to go beyond the management of pain per se if they are to achieve success. This evidence-based review of the assessment of the patient with pain in diabetes addresses the state-of-the-art management of pain, recognizing all the conditions that produce pain in diabetes and the evidence in support of a variety of treatments currently available. A search of the full Medline database for the last 10 years was conducted in August 2012 using the terms painful diabetic peripheral neuropathy, painful diabetic peripheral polyneuropathy, painful diabetic neuropathy and pain in diabetes. In addition, recent reviews addressing this issue were adopted as necessary. In particular, reports from the American Academy of Neurology and the Toronto Consensus Panel on Diabetic Neuropathy were included. Unfortunately, the results of evidence-based studies do not necessarily take into account the presence of comorbidities, the cost of treatment, or the role of third-party payers in decision-making. Thus, this review attempts to give a more balanced view of the management of pain in the diabetic patient with neuropathy and in particular the role of pregabalin. PMID:23467255

Guidelines in the management of diabetic nerve pain: clinical utility of pregabalin.

PubMed

Vinik, Aaron I; Casellini, Carolina M

2013-01-01

Diabetic peripheral neuropathy is a common complication of diabetes. It presents as a variety of syndromes for which there is no universally accepted unique classification. Sensorimotor polyneuropathy is the most common type, affecting about 30% of diabetic patients in hospital care and 25% of those in the community. Pain is the reason for 40% of patient visits in a primary care setting, and about 20% of these have had pain for greater than 6 months. Chronic pain may be nociceptive, which occurs as a result of disease or damage to tissue with no abnormality in the nervous system. In contrast, neuropathic pain is defined as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system." Persistent neuropathic pain interferes significantly with quality of life, impairing sleep and recreation; it also significantly impacts emotional well-being, and is associated with depression, anxiety, and noncompliance with treatment. Painful diabetic peripheral neuropathy is a difficult-to-manage clinical problem, and patients with this condition are more apt to seek medical attention than those with other types of diabetic neuropathy. Early recognition of psychological problems is critical to the management of pain, and physicians need to go beyond the management of pain per se if they are to achieve success. This evidence-based review of the assessment of the patient with pain in diabetes addresses the state-of-the-art management of pain, recognizing all the conditions that produce pain in diabetes and the evidence in support of a variety of treatments currently available. A search of the full Medline database for the last 10 years was conducted in August 2012 using the terms painful diabetic peripheral neuropathy, painful diabetic peripheral polyneuropathy, painful diabetic neuropathy and pain in diabetes. In addition, recent reviews addressing this issue were adopted as necessary. In particular, reports from the American Academy of Neurology and the Toronto Consensus Panel on Diabetic Neuropathy were included. Unfortunately, the results of evidence-based studies do not necessarily take into account the presence of comorbidities, the cost of treatment, or the role of third-party payers in decision-making. Thus, this review attempts to give a more balanced view of the management of pain in the diabetic patient with neuropathy and in particular the role of pregabalin.

Clinical relevance and biology of circulating tumor cells

PubMed Central

2011-01-01

Most breast cancer patients die due to metastases, and the early onset of this multistep process is usually missed by current tumor staging modalities. Therefore, ultrasensitive techniques have been developed to enable the enrichment, detection, isolation and characterization of disseminated tumor cells in bone marrow and circulating tumor cells in the peripheral blood of cancer patients. There is increasing evidence that the presence of these cells is associated with an unfavorable prognosis related to metastatic progression in the bone and other organs. This review focuses on investigations regarding the biology and clinical relevance of circulating tumor cells in breast cancer. PMID:22114869

Monitoring peripheral perfusion and microcirculation.

PubMed

Dubin, Arnaldo; Henriquez, Elizabeth; Hernández, Glenn

2018-06-01

Microcirculatory alterations play a major role in the pathogenesis of shock. Monitoring tissue perfusion might be a relevant goal for shock resuscitation. The goal of this review was to revise the evidence supporting the monitoring of peripheral perfusion and microcirculation as goals of resuscitation. For this purpose, we mainly focused on skin perfusion and sublingual microcirculation. Although there are controversies about the reproducibility of capillary refill time in monitoring peripheral perfusion, it is a sound physiological variable and suitable for the ICU settings. In addition, observational studies showed its strong ability to predict outcome. Moreover, a preliminary study suggested that it might be a valuable goal for resuscitation. These results should be confirmed by the ongoing ANDROMEDA-SHOCK randomized controlled trial. On the other hand, the monitoring of sublingual microcirculation might also provide relevant physiological and prognostic information. On the contrary, methodological drawbacks mainly related to video assessment hamper its clinical implementation at the present time. Measurements of peripheral perfusion might be useful as goal of resuscitation. The results of the ANDROMEDA-SHOCK will clarify the role of skin perfusion as a guide for the treatment of shock. In contrast, the assessment of sublingual microcirculation mainly remains as a research tool.

Strategies to promote peripheral nerve regeneration: electrical stimulation and/or exercise

PubMed Central

Gordon, Tessa; English, Arthur W.

2015-01-01

Enhancing the regeneration of axons is often considered a therapeutic target for improving functional recovery after peripheral nerve injury. In this review, the evidence for the efficacy of electrical stimulation (ES), daily exercise, and their combination in promoting nerve regeneration after peripheral nerve injuries in both animal models and in human patients, is explored. The rationale, effectiveness, and molecular basis of ES and exercise in accelerating axon outgrowth are reviewed. In comparing the effects of ES and exercise in enhancing axon regeneration, increased neural activity, neurotrophins, and androgens are considered common requirements. Similar, gender-specific requirements are found for exercise to enhance axon regeneration in the periphery and for sustaining synaptic inputs onto injured motoneurons. ES promotes nerve regeneration after delayed nerve repair in humans and rats. The effectiveness of exercise is less clear. Although ES, but not exercise, results in a significant misdirection of regenerating motor axons to reinnervate different muscle targets, the loss of neuromuscular specificity encountered has only a very small impact on resulting functional recovery. Both ES and exercise are promising experimental treatments for peripheral nerve injury that seem ready to be translated to clinical use. PMID:26121368

Effect of Vitamin E on Oxaliplatin-induced Peripheral Neuropathy Prevention: A Randomized Controlled Trial

PubMed Central

Salehi, Zeinab; Roayaei, Mahnaz

2015-01-01

Background: Peripheral neuropathy is one of the most important limitations of oxaliplatin base regimen, which is the standard for the treatment of colorectal cancer. Evidence has shown that Vitamin E may be protective in chemotherapy-induced peripheral neuropathy. The aim of this study is to evaluate the effect of Vitamin E administration on prevention of oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer. Methods: This was a prospective randomized, controlled clinical trial. Patients with colorectal cancer and scheduled to receive oxaliplatin-based regimens were enrolled in this study. Enrolled patients were randomized into two groups. The first group received Vitamin E at a dose of 400 mg daily and the second group observed, until after the sixth course of the oxaliplatin regimen. For oxaliplatin-induced peripheral neuropathy assessment, we used the symptom experience diary questionnaire that completed at baseline and after the sixth course of chemotherapy. Only patients with a score of zero at baseline were eligible for this study. Results: Thirty-two patients were randomized to the Vitamin E group and 33 to the control group. There was no difference in the mean peripheral neuropathy score changes (after − before) between two groups, after sixth course of the oxaliplatin base regimen (mean difference [after − before] of Vitamin E group = 6.37 ± 2.85, control group = 6.57 ± 2.94; P = 0.78). Peripheral neuropathy scores were significantly increased after intervention compared with a base line in each group (P < 0.001). Conclusions: The results from this current trial demonstrate a lack of benefit for Vitamin E in preventing oxaliplatin-induced peripheral neuropathy. PMID:26682028

Connexin32 expression in central and peripheral nervous systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deschenes, S.M.; Scherer, S.S.; Fischbeck, K.H.

1994-09-01

Mutations have been identified in the gap junction gene, connexin32 (Cx32), in patients affected with the X-linked form of the demyelinating neuropathy, Charcot-Marie-Tooth disease (CMTX). Gap junctions composed of Cx32 are present and developmentally regulated in a wide variety of tissues. In peripheral nerve, our immunohistochemical analysis localized Cx32 to the noncompacted myelin of the paranodal regions and the Schmidt-Lantermann incisures, where previous studies describe gap junctions. In contrast to the location of Cx32 in peripheral nerve and the usual restriction of clinical manifestations to the peripheral nervous system (PNS) (abstract by Paulson describes an exception), preliminary studies show thatmore » Cx32 is present in the compacted myelin of the central nervous system (CNS), as demonstrated by radial staining through the myelin sheath of oligodendrocytes in rat spinal cord. Analysis of Cx32 expression in various regions of rat CNS during development shows that the amount of Cx32 mRNA and protein increases as myelination increases, a pattern observed for other myelin genes. Studies in the PNS provide additional evidence that Cx32 and myelin genes are coordinately regulated at the transcriptional level; Cx32 and peripheral myelin gene PMP-22 mRNAs are expressed in parallel following transient or permanent nerve injury. Differences in post-translational regulation of Cx32 in the CNS and PNS may be indicated by the presence of a faster migrating form of Cs32 in cerebrum versus peripheral nerve. Studies are currently underway to determine the unique role of Cx32 in peripheral nerve.« less

Clinical data, clinicopathologic findings and outcome in dogs with amegakaryocytic thrombocytopenia and primary immune-mediated thrombocytopenia.

PubMed

Cooper, S A; Huang, A A; Raskin, R E; Weng, H-Y; Scott-Moncrieff, J C

2016-03-01

The aim of this study was to identify distinguishing characteristics between dogs diagnosed with amegakaryocytic thrombocytopenia and those diagnosed with presumed primary peripheral immune-mediated thrombocytopenia. Presenting clinical and clinicopathologic data and outcomes were compared between the two groups. Retrospective study performed on seven client-owned dogs diagnosed with amegakaryocytic thrombocytopenia and 34 client-owned dogs with primary peripheral immune-mediated thrombocytopenia. All dogs in the amegakaryocytic thrombocytopenia group were anaemic on presentation with a median haematocrit of 23% (range 9·4 to 36), while the primary peripheral immune-mediated thrombocytopoenia group had a median presenting haematocrit of 35% (range 10 to 53). Dogs with amegakaryocytic thrombocytopenia had a median of five (range 4 to 7) clinical signs of bleeding compared to a median of three (range 0 to 6) in the primary peripheral immune-mediated thrombocytopenia group with 86% (6 of 7) of amegakaryocytic thrombocytopenia dogs requiring a blood transfusion compared to 41% (14 of 34) of primary peripheral immune-mediated thrombocytopenia dogs. Six of the seven amegakaryocytic thrombocytopenia dogs did not survive to discharge, while only five of the 34 primary peripheral immune-mediated thrombocytopenia dogs did not survive to discharge. The clinical presentation of dogs with amegakaryocytic thrombocytopenia and primary peripheral immune-mediated thrombocytopenia is similar, but dogs with amegakaryocytic thrombocytopenia had a more severe clinical course compared to primary peripheral immune-mediated thrombocytopenia dogs. The prognosis for dogs with amegakaryocytic thrombocytopenia is poor. © 2016 British Small Animal Veterinary Association.

Plasmodium cynomolgi infections in rhesus macaques display clinical and parasitological features pertinent to modelling vivax malaria pathology and relapse infections.

PubMed

Joyner, Chester; Moreno, Alberto; Meyer, Esmeralda V S; Cabrera-Mora, Monica; Kissinger, Jessica C; Barnwell, John W; Galinski, Mary R

2016-09-02

Plasmodium vivax infections in humans or in new world monkeys pose research challenges that necessitate the use of alternative model systems. Plasmodium cynomolgi is a closely related species that shares genetic and biological characteristics with P. vivax, including relapses. Here, the haematological dynamics and clinical presentation of sporozoite-initiated P. cynomolgi infections in Macaca mulatta (rhesus macaques) are evaluated over a 100-day period. Five M. mulatta were inoculated with 2000 P. cynomolgi B strain sporozoites. Parasitological and haematological data were collected daily to study the clinical presentations of primary infections and relapses. Peripheral blood and bone marrow aspirates were collected at specific time points during infection for future and retrospective systems biology analyses. Patent infections were observed between days 10 and 12, and the acute, primary infection consisted of parasitaemias ranging from 269,962 to 1,214,842 parasites/µl (4.42-19.5 % parasitaemia). All animals presented with anaemia, ranging from moderate (7-10 g/dl) to severe (<7 g/dl), based on peripheral haemoglobin concentrations. Minimum haemoglobin levels coincided with the clearance of parasites and peripheral reticulocytosis was evident at this time. Mild thrombocytopaenia (<150,000 platelets/µl) was observed in all animals, but unlike haemoglobin, platelets were lowest whenever peripheral parasitaemia peaked. The animals' conditions were classified as non-severe, severe or lethal (in one case) based upon their clinical presentation. The lethal phenotype presented uniquely with an exceptionally high parasitaemia (19.5 %) and lack of a modest reticulocyte release, which was observed in the other animals prior to acute manifestations. One or two relapses were observed in the four surviving animals, and these were characterized by significantly lower parasitaemias and minimal changes in clinical parameters compared to pre-infection values. Rhesus macaque infections initiated by P. cynomolgi B strain sporozoites recapitulated pathology of human malaria, including anaemia and thrombocytopaenia, with inter-individual differences in disease severity. Importantly, this study provides an in-depth assessment of clinical and parasitological data, and shows that unlike the primary infections, the relapses did not cause clinical malaria. Notably, this body of research has provided experimental plans, large accessible datasets, and blood and bone marrow samples pertinent for ongoing and iterative systems biology investigations.

Mechanisms of peripheral immune-cell-mediated analgesia in inflammation: clinical and therapeutic implications.

PubMed

Hua, Susan; Cabot, Peter J

2010-09-01

Peripheral mechanisms of endogenous pain control are significant. In peripheral inflamed tissue, an interaction between immune-cell-derived opioids and opioid receptors localized on sensory nerve terminals results in potent, clinically measurable analgesia. Opioid peptides and the mRNA encoding their precursor proteins are present in immune cells. These cells 'home' preferentially to injured tissue, where they secrete opioids to reduce pain. Investigation of the mechanisms underlying the migration of opioid-containing immune cells to inflamed tissue is an active area of research, with recent data demonstrating the importance of cell adhesion molecules in leukocyte adhesion to both the endothelium in vascular transmigration and to neurons within peripheral inflamed tissue. This review summarizes the physiological mechanisms and clinical significance of this unique endogenous peripheral analgesic pathway and discusses therapeutic implications for the development of novel targeted peripheral analgesics. Copyright 2010 Elsevier Ltd. All rights reserved.

Clinical relevance of metronidazole and peripheral neuropathy: a systematic review of the literature.

PubMed

Goolsby, Tiffany A; Jakeman, Bernadette; Gaynes, Robert P

2018-03-01

The objective of this paper was to review and evaluate the literature on metronidazole-associated peripheral neuropathy and determine the relevance in clinical practice. MEDLINE/PubMed, EBSCO, and Google Scholar were searched through February 2017 using the search terms metronidazole and peripheral neuropathy, or polyneuropathy, or paresthesia, or neurotoxicity. Relevant case reports, retrospective studies, surveys, and review articles were included. Bibliographies of all relevant articles were reviewed for additional sources. Overall, metronidazole is generally well tolerated, but serious neurotoxicity, including peripheral neuropathy, has been reported. The overall incidence of peripheral neuropathy associated with metronidazole is unknown. Our review found 36 case reports (40 unique patients) of metronidazole-associated peripheral neuropathy, with most cases (31/40) receiving a >42 g total (>4 weeks) of therapy. In addition, we reviewed 13 clinical studies and found varying rates of peripheral neuropathy from 0 to 50%. Within these clinical studies, we found a higher incidence of peripheral neuropathy in patients receiving >42 g total (>4 weeks) of metronidazole compared with those patients receiving ≤42 g total (17.9% vs. 1.7%). Nearly all patients had complete resolution of symptoms. In conclusion, peripheral neuropathy is rare in patients who receive ≤42 g total of metronidazole. Patients who receive higher total doses may be at higher risk of peripheral neuropathy, but symptoms resolve after discontinuation of therapy in most patients. Antimicrobial stewardship programs may consider use of antibiotic combinations that include metronidazole over broad-spectrum alternatives when treating with ≤42 g total of the drug (≤4 weeks). Published by Elsevier B.V.

Cafestol, a coffee-specific diterpene, induces peripheral antinociception mediated by endogenous opioid peptides.

PubMed

Guzzo, Luciana S; Perez, Andrea C; Romero, Thiago Rl; Azevedo, Adolfo O; Duarte, Igor Dg

2012-05-01

The opioid peptides have been implicated in peripheral antinociception induced by non-opioidergic compounds, including non-steroidal anti-inflammatory drugs and α(2) -adrenoceptor agonists. The aims of the present study were to investigate the possible peripheral antinociceptive effect of cafestol, a diterpene present in the oil derived from coffee beans, and to evaluate the involvement of opioid peptides in its effect. The rat paw pressure test was used to assess antinocipeptive effects. Hyperalgesia was induced by intraplantar injection of prostaglandin E(2) (2 μg/paw). All drugs were locally administered into the hind-paws of male Wistar rats. Intraplantar injection of cafestol (20, 40 and 80 μg) induced peripheral antinociception. The antinociceptive effect of cafestol was due to a local action because the higher dose (80 μg/paw) did not produce any effect in the contralateral paw. The opioid receptor antagonist naloxone (25, 50 and 100 μg/paw) prevented the action of cafestol (80 μg/paw), whereas the aminopeptidase inhibitor bestatin (400 μg/paw) potentiated the antinociceptive effect of cafestol (40 μg/paw). The results of the present study provide evidence that cafestol treatment has a peripheral antinociceptive effect and suggest that this effect is mediated by the release of endogenous opioids. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd.

Is there a rural gradient in the diagnosis of aortic stenosis? An analysis of a remote Scottish cohort.

PubMed

Maycock, Matthew I; Farman, Colin; Mort, Alasdair; Turpie, David; Leslie, Stephen J

2013-01-01

Calcific aortic stenosis is the most common cardiac valve lesion and is becoming increasingly prevalent as life expectancy rises. There is evidence that patients in remote and rural areas with certain diseases have worse outcomes and present to specialist services later than their urban counterparts. It is not known whether patients with aortic stenosis follow a similar pattern. The aim of this study was to investigate whether increasing rurality was associated with later presentation to healthcare services at a more advanced stage of aortic stenosis. This was a retrospective cohort study. Using ICD-10 discharge codes and local databases, 605 patients with aortic stenosis who presented between 31 November 1999 and 1 December 2008 were identified. Aortic stenosis was defined as a pressure gradient across the aortic valve of 25 mmHg or more. Patients with prior aortic valve replacement were excluded. Clinical notes were reviewed for all patients. Gender, age and pressure gradient across the aortic valve at presentation and patient GP-practice location were recorded. Patients were then assigned a Clinical Peripherality Index score based on the postcode of their GP's practice to define rurality. Patient data were compared across the six defined levels of clinical peripherality by ANOVA. Mean patient age was 73 ± 13 years, and 336 (54%) were male. The peak gradient across the valve was 41.1 ± 26.7 mmHg. There was no association between the level of clinical peripherality and the stage of aortic stenosis at presentation, age or gender (all p >0.05). There was no urban-rural gradient in the severity of aortic stenosis at presentation in this remote Scottish cohort. This suggests that patients with this condition in remote areas do not present later in their disease trajectory.

Advances and Future Applications of Augmented Peripheral Nerve Regeneration

PubMed Central

Jones, Salazar; Eisenberg, Howard M.; Jia, Xiaofeng

2016-01-01

Peripheral nerve injuries remain a significant source of long lasting morbidity, disability, and economic costs. Much research continues to be performed in areas related to improving the surgical outcomes of peripheral nerve repair. In this review, the physiology of peripheral nerve regeneration and the multitude of efforts to improve surgical outcomes are discussed. Improvements in tissue engineering that have allowed for the use of synthetic conduits seeded with neurotrophic factors are highlighted. Selected pre-clinical and available clinical data using cell based methods such as Schwann cell, undifferentiated, and differentiated stem cell transplantation to guide and enhance peripheral nerve regeneration are presented. The limitations that still exist in the utility of neurotrophic factors and cell-based therapies are outlined. Strategies that are most promising for translation into the clinical arena are suggested. PMID:27618010

Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient.

PubMed

Murray, Michael J; DeBlock, Heidi; Erstad, Brian; Gray, Anthony; Jacobi, Judi; Jordan, Che; McGee, William; McManus, Claire; Meade, Maureen; Nix, Sean; Patterson, Andrew; Sands, M Karen; Pino, Richard; Tescher, Ann; Arbour, Richard; Rochwerg, Bram; Murray, Catherine Friederich; Mehta, Sangeeta

2016-11-01

To update the 2002 version of "Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient." A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided. Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommendations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which insufficient evidence was available to create a profile. Task Force members reviewed this material and all available evidence and provided recommendations, suggestions, or good practice statements for these 21 questions. The Task Force developed a single strong recommendation: we recommend scheduled eye care that includes lubricating drops or gel and eyelid closure for patients receiving continuous infusions of neuromuscular-blocking agents. The Task Force developed 10 weak recommendations. 1) We suggest that a neuromuscular-blocking agent be administered by continuous intravenous infusion early in the course of acute respiratory distress syndrome for patients with a PaO2/FIO2 less than 150. 2) We suggest against the routine administration of an neuromuscular-blocking agents to mechanically ventilated patients with status asthmaticus. 3) We suggest a trial of a neuromuscular-blocking agents in life-threatening situations associated with profound hypoxemia, respiratory acidosis, or hemodynamic compromise. 4) We suggest that neuromuscular-blocking agents may be used to manage overt shivering in therapeutic hypothermia. 5) We suggest that peripheral nerve stimulation with train-of-four monitoring may be a useful tool for monitoring the depth of neuromuscular blockade but only if it is incorporated into a more inclusive assessment of the patient that includes clinical assessment. 6) We suggest against the use of peripheral nerve stimulation with train of four alone for monitoring the depth of neuromuscular blockade in patients receiving continuous infusion of neuromuscular-blocking agents. 7) We suggest that patients receiving a continuous infusion of neuromuscular-blocking agent receive a structured physiotherapy regimen. 8) We suggest that clinicians target a blood glucose level of less than 180 mg/dL in patients receiving neuromuscular-blocking agents. 9) We suggest that clinicians not use actual body weight and instead use a consistent weight (ideal body weight or adjusted body weight) when calculating neuromuscular-blocking agents doses for obese patients. 10) We suggest that neuromuscular-blocking agents be discontinued at the end of life or when life support is withdrawn. In situations in which evidence was lacking or insufficient and the study results were equivocal or optimal clinical practice varies, the Task Force made no recommendations for nine of the topics. 1) We make no recommendation as to whether neuromuscular blockade is beneficial or harmful when used in patients with acute brain injury and raised intracranial pressure. 2) We make no recommendation on the routine use of neuromuscular-blocking agents for patients undergoing therapeutic hypothermia following cardiac arrest. 3) We make no recommendation on the use of peripheral nerve stimulation to monitor degree of block in patients undergoing therapeutic hypothermia. 4) We make no recommendation on the use of neuromuscular blockade to improve the accuracy of intravascular-volume assessment in mechanically ventilated patients. 5) We make no recommendation concerning the use of electroencephalogram-derived parameters as a measure of sedation during continuous administration of neuromuscular-blocking agents. 6) We make no recommendation regarding nutritional requirements specific to patients receiving infusions of neuromuscular-blocking agents. 7) We make no recommendation concerning the use of one measure of consistent weight over another when calculating neuromuscular-blocking agent doses in obese patients. 8) We make no recommendation on the use of neuromuscular-blocking agents in pregnant patients. 9) We make no recommendation on which muscle group should be monitored in patients with myasthenia gravis receiving neuromuscular-blocking agents. Finally, in situations in which evidence was lacking or insufficient but expert consensus was unanimous, the Task Force developed six good practice statements. 1) If peripheral nerve stimulation is used, optimal clinical practice suggests that it should be done in conjunction with assessment of other clinical findings (e.g., triggering of the ventilator and degree of shivering) to assess the degree of neuromuscular blockade in patients undergoing therapeutic hypothermia. 2) Optimal clinical practice suggests that a protocol should include guidance on neuromuscular-blocking agent administration in patients undergoing therapeutic hypothermia. 3) Optimal clinical practice suggests that analgesic and sedative drugs should be used prior to and during neuromuscular blockade, with the goal of achieving deep sedation. 4) Optimal clinical practice suggests that clinicians at the bedside implement measure to attenuate the risk of unintended extubation in patients receiving neuromuscular-blocking agents. 5) Optimal clinical practice suggests that a reduced dose of an neuromuscular-blocking agent be used for patients with myasthenia gravis and that the dose should be based on peripheral nerve stimulation with train-of-four monitoring. 6) Optimal clinical practice suggests that neuromuscular-blocking agents be discontinued prior to the clinical determination of brain death.

Neuropathic ocular pain: an important yet underevaluated feature of dry eye

PubMed Central

Galor, A; Levitt, R C; Felix, E R; Martin, E R; Sarantopoulos, C D

2015-01-01

Dry eye has gained recognition as a public health problem given its prevalence, morbidity, and cost implications. Dry eye can have a variety of symptoms including blurred vision, irritation, and ocular pain. Within dry eye-associated ocular pain, some patients report transient pain whereas others complain of chronic pain. In this review, we will summarize the evidence that chronicity is more likely to occur in patients with dysfunction in their ocular sensory apparatus (ie, neuropathic ocular pain). Clinical evidence of dysfunction includes the presence of spontaneous dysesthesias, allodynia, hyperalgesia, and corneal nerve morphologic and functional abnormalities. Both peripheral and central sensitizations likely play a role in generating the noted clinical characteristics. We will further discuss how evaluating for neuropathic ocular pain may affect the treatment of dry eye-associated chronic pain. PMID:25376119

Transcutaneous Electrical Nerve Stimulation (TENS) A Possible Aid for Pain Relief in Developing Countries?

PubMed Central

Tashani, O; Johnson, MI

2009-01-01

Transcutaneous electrical nerve stimulation (TENS) refers to the delivery of electrical currents through the skin to activate peripheral nerves. The technique is widely used in developed countries to relieve a wide range of acute and chronic pain conditions, including pain resulting from cancer and its treatment. There are many systematic reviews on TENS although evidence is often inconclusive because of shortcomings in randomised control trials methodology. In this overview the basic science behind TENS will be discussed, the evidence of its effectiveness in specific clinical conditions analysed and a case for its use in pain management in developing countries will be made. PMID:21483510

Clinical peripherality: development of a peripherality index for rural health services.

PubMed

Swan, Gillian M; Selvaraj, Sivasubramaniam; Godden, David J

2008-01-25

The configuration of rural health services is influenced by geography. Rural health practitioners provide a broader range of services to smaller populations scattered over wider areas or more difficult terrain than their urban counterparts. This has implications for training and quality assurance of outcomes. This exploratory study describes the development of a "clinical peripherality" indicator that has potential application to remote and rural general practice communities for planning and research purposes. Profiles of general practice communities in Scotland were created from a variety of public data sources. Four candidate variables were chosen that described demographic and geographic characteristics of each practice: population density, number of patients on the practice list, travel time to nearest specialist led hospital and travel time to Health Board administrative headquarters. A clinical peripherality index, based on these variables, was derived using factor analysis. Relationships between the clinical peripherality index and services offered by the practices and the staff profile of the practices were explored in a series of univariate analyses. Factor analysis on the four candidate variables yielded a robust one-factor solution explaining 75% variance with factor loadings ranging from 0.83 to 0.89. Rural and remote areas had higher median values and a greater scatter of clinical peripherality indices among their practices than an urban comparison area. The range of services offered and the profile of staffing of practices was associated with the peripherality index. Clinical peripherality is determined by the nature of the practice and its location relative to secondary care and administrative and educational facilities. It has features of both gravity model-based and travel time/accessibility indicators and has the potential to be applied to training of staff for rural and remote locations and to other aspects of health policy and planning. It may assist planners in conceptualising the effects on general practices of centralising specialist clinical services or administrative and educational facilities.

Clinical peripherality: development of a peripherality index for rural health services

PubMed Central

Swan, Gillian M; Selvaraj, Sivasubramaniam; Godden, David J

2008-01-01

Background The configuration of rural health services is influenced by geography. Rural health practitioners provide a broader range of services to smaller populations scattered over wider areas or more difficult terrain than their urban counterparts. This has implications for training and quality assurance of outcomes. This exploratory study describes the development of a "clinical peripherality" indicator that has potential application to remote and rural general practice communities for planning and research purposes. Methods Profiles of general practice communities in Scotland were created from a variety of public data sources. Four candidate variables were chosen that described demographic and geographic characteristics of each practice: population density, number of patients on the practice list, travel time to nearest specialist led hospital and travel time to Health Board administrative headquarters. A clinical peripherality index, based on these variables, was derived using factor analysis. Relationships between the clinical peripherality index and services offered by the practices and the staff profile of the practices were explored in a series of univariate analyses. Results Factor analysis on the four candidate variables yielded a robust one-factor solution explaining 75% variance with factor loadings ranging from 0.83 to 0.89. Rural and remote areas had higher median values and a greater scatter of clinical peripherality indices among their practices than an urban comparison area. The range of services offered and the profile of staffing of practices was associated with the peripherality index. Conclusion Clinical peripherality is determined by the nature of the practice and its location relative to secondary care and administrative and educational facilities. It has features of both gravity model-based and travel time/accessibility indicators and has the potential to be applied to training of staff for rural and remote locations and to other aspects of health policy and planning. It may assist planners in conceptualising the effects on general practices of centralising specialist clinical services or administrative and educational facilities. PMID:18221533

[Peripheral refraction: cause or effect of refraction development?

PubMed

Tarutta, E P; Iomdina, E N; Kvaratskheliya, N G; Milash, S V; Kruzhkova, G V

to study peripheral refraction and the shape of the eyeball in children with different clinical refraction. Using an original method, peripheral refraction was measured at 10-12 degrees temporally and nasally from the fovea in 56 right eyes with different clinical, or axial, refraction of 20 boys and 36 girls aged 7 to 16 years (11.9±1.17 years on average). The shape of the eyeball was judged of by the ratio of its anterior-posterior axial length (AL) to horizontal diameter (HD). The incidence and value of peripheral myopic defocus in children appeared to decrease with clinical refraction increasing from high hyperopia to high myopia. This was the first time, mixed peripheral refraction was found in children, occurring more frequently in higher myopia. This mixed peripheral defocus, shown to be a transitional stage between relative peripheral myopia and relative hyperopia, indicates non-uniform stretching of posterior pole tissues in the course of refraction development and myopia progression. As ocular refraction increases from high hyperopia to high myopia, the growth of AL outpaces that of HD. Obviously, natural peripheral defocus results from changes in size and shape of the eyeball in the course of refraction development.

Peripheral Neuropathy: A Practical Approach to Diagnosis and Symptom Management.

PubMed

Watson, James C; Dyck, P James B

2015-07-01

Peripheral neuropathy is one of the most prevalent neurologic conditions encountered by physicians of all specialties. Physicians are faced with 3 distinct challenges in caring for patients with peripheral neuropathy: (1) how to efficiently and effectively screen (in less than 2 minutes) an asymptomatic patient for peripheral neuropathy when they have a disorder in which peripheral neuropathy is highly prevalent (eg, diabetes mellitus), (2) how to clinically stratify patients presenting with symptoms of neuropathy to determine who would benefit from specialty consultation and what testing is appropriate for those who do not need consultation, and (3) how to treat the symptoms of painful peripheral neuropathy. In this concise review, we address these 3 common clinical scenarios. Easily defined clinical patterns of involvement are used to identify patients in need of neurologic consultation, the yield of laboratory and other diagnostic testing is reviewed for the evaluation of length-dependent, sensorimotor peripheral neuropathies (the most common form of neuropathy), and an algorithmic approach with dosing recommendations is provided for the treatment of neuropathic pain associated with peripheral neuropathy. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Registry Assessment of Peripheral Interventional Devices (RAPID)　- Registry Assessment of Peripheral Interventional Devices Core Data Elements.

PubMed

Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L; Nc, Durham; Md, Silver Spring; Japan, Tokyo; Ny, New York; Ri, Providence; Vt, Burlington; Mass, Newton; Colo, Denver; Ariz, Tempe; Calif, Santa Clara; Minn, Minneapolis; Nh, Lebanon

2018-01-25

The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible.Methods and Results:Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators.

Antimicrobial resistance pattern of Neisseria gonorrhoeae isolates from peripheral health centres and STD clinic attendees of a tertiary care centre in India.

PubMed

Bala, M; Ray, K; Gupta, S M

2008-06-01

The aim of the study was to compare the antimicrobial resistance pattern of Neisseria gonorrhoeae isolates from urban and rural peripheral health centres and from sexually transmitted disease (STD) clinic attendees. Antimicrobial susceptibility testing of 191 N. gonorrhoeae isolates (165 isolates from STD clinic attendees and 26 from peripheral health centres) was carried out in Delhi, India, using the calibrated dichotomous sensitivity technique for penicillin, tetracycline, ceftriaxone, ciprofloxacin, spectinomycin and nalidixic acid, and minimum inhibitory concentrations were determined using E-test. Penicillin-resistant, ciprofloxacin-resistant, penicillinase-producing N. gonorrhoeae and tetracycline-resistant N. gonorrhoeae strains were higher in STD clinic attendees than in peripheral health centres, probably because of less antibiotic pressure in the peripheral areas. High-level resistance to ciprofloxacin and multiresistant strains were also higher in STD clinic attendees. The present study emphasizes the importance of surveillance of antimicrobial resistance of N. gonorrhoeae in different population subgroups in order to monitor the spread of multiresistant strains and to update the national treatment recommendations.

Contribution of systemic and somatic factors to clinical response and resistance to PD-L1 blockade in urothelial cancer: An exploratory multi-omic analysis

PubMed Central

Ahuja, Arun; Al-Ahmadie, Hikmat; Yusko, Erik; Benzeno, Sharon; Boyd, Mariel; Moran, Meredith; Iyer, Gopa; Mardis, Elaine R.

2017-01-01

Background Inhibition of programmed death-ligand 1 (PD-L1) with atezolizumab can induce durable clinical benefit (DCB) in patients with metastatic urothelial cancers, including complete remissions in patients with chemotherapy refractory disease. Although mutation load and PD-L1 immune cell (IC) staining have been associated with response, they lack sufficient sensitivity and specificity for clinical use. Thus, there is a need to evaluate the peripheral blood immune environment and to conduct detailed analyses of mutation load, predicted neoantigens, and immune cellular infiltration in tumors to enhance our understanding of the biologic underpinnings of response and resistance. Methods and findings The goals of this study were to (1) evaluate the association of mutation load and predicted neoantigen load with therapeutic benefit and (2) determine whether intratumoral and peripheral blood T cell receptor (TCR) clonality inform clinical outcomes in urothelial carcinoma treated with atezolizumab. We hypothesized that an elevated mutation load in combination with T cell clonal dominance among intratumoral lymphocytes prior to treatment or among peripheral T cells after treatment would be associated with effective tumor control upon treatment with anti-PD-L1 therapy. We performed whole exome sequencing (WES), RNA sequencing (RNA-seq), and T cell receptor sequencing (TCR-seq) of pretreatment tumor samples as well as TCR-seq of matched, serially collected peripheral blood, collected before and after treatment with atezolizumab. These parameters were assessed for correlation with DCB (defined as progression-free survival [PFS] >6 months), PFS, and overall survival (OS), both alone and in the context of clinical and intratumoral parameters known to be predictive of survival in this disease state. Patients with DCB displayed a higher proportion of tumor-infiltrating T lymphocytes (TIL) (n = 24, Mann-Whitney p = 0.047). Pretreatment peripheral blood TCR clonality below the median was associated with improved PFS (n = 29, log-rank p = 0.048) and OS (n = 29, log-rank p = 0.011). Patients with DCB also demonstrated more substantial expansion of tumor-associated TCR clones in the peripheral blood 3 weeks after starting treatment (n = 22, Mann-Whitney p = 0.022). The combination of high pretreatment peripheral blood TCR clonality with elevated PD-L1 IC staining in tumor tissue was strongly associated with poor clinical outcomes (n = 10, hazard ratio (HR) (mean) = 89.88, HR (median) = 23.41, 95% CI [2.43, 506.94], p(HR > 1) = 0.0014). Marked variations in mutation loads were seen with different somatic variant calling methodologies, which, in turn, impacted associations with clinical outcomes. Missense mutation load, predicted neoantigen load, and expressed neoantigen load did not demonstrate significant association with DCB (n = 25, Mann-Whitney p = 0.22, n = 25, Mann-Whitney p = 0.55, and n = 25, Mann-Whitney p = 0.29, respectively). Instead, we found evidence of time-varying effects of somatic mutation load on PFS in this cohort (n = 25, p = 0.044). A limitation of our study is its small sample size (n = 29), a subset of the patients treated on IMvigor 210 (NCT02108652). Given the number of exploratory analyses performed, we intend for these results to be hypothesis-generating. Conclusions These results demonstrate the complex nature of immune response to checkpoint blockade and the compelling need for greater interrogation and data integration of both host and tumor factors. Incorporating these variables in prospective studies will facilitate identification and treatment of resistant patients. PMID:28552987

Contribution of systemic and somatic factors to clinical response and resistance to PD-L1 blockade in urothelial cancer: An exploratory multi-omic analysis.

PubMed

Snyder, Alexandra; Nathanson, Tavi; Funt, Samuel A; Ahuja, Arun; Buros Novik, Jacqueline; Hellmann, Matthew D; Chang, Eliza; Aksoy, Bulent Arman; Al-Ahmadie, Hikmat; Yusko, Erik; Vignali, Marissa; Benzeno, Sharon; Boyd, Mariel; Moran, Meredith; Iyer, Gopa; Robins, Harlan S; Mardis, Elaine R; Merghoub, Taha; Hammerbacher, Jeff; Rosenberg, Jonathan E; Bajorin, Dean F

2017-05-01

Inhibition of programmed death-ligand 1 (PD-L1) with atezolizumab can induce durable clinical benefit (DCB) in patients with metastatic urothelial cancers, including complete remissions in patients with chemotherapy refractory disease. Although mutation load and PD-L1 immune cell (IC) staining have been associated with response, they lack sufficient sensitivity and specificity for clinical use. Thus, there is a need to evaluate the peripheral blood immune environment and to conduct detailed analyses of mutation load, predicted neoantigens, and immune cellular infiltration in tumors to enhance our understanding of the biologic underpinnings of response and resistance. The goals of this study were to (1) evaluate the association of mutation load and predicted neoantigen load with therapeutic benefit and (2) determine whether intratumoral and peripheral blood T cell receptor (TCR) clonality inform clinical outcomes in urothelial carcinoma treated with atezolizumab. We hypothesized that an elevated mutation load in combination with T cell clonal dominance among intratumoral lymphocytes prior to treatment or among peripheral T cells after treatment would be associated with effective tumor control upon treatment with anti-PD-L1 therapy. We performed whole exome sequencing (WES), RNA sequencing (RNA-seq), and T cell receptor sequencing (TCR-seq) of pretreatment tumor samples as well as TCR-seq of matched, serially collected peripheral blood, collected before and after treatment with atezolizumab. These parameters were assessed for correlation with DCB (defined as progression-free survival [PFS] >6 months), PFS, and overall survival (OS), both alone and in the context of clinical and intratumoral parameters known to be predictive of survival in this disease state. Patients with DCB displayed a higher proportion of tumor-infiltrating T lymphocytes (TIL) (n = 24, Mann-Whitney p = 0.047). Pretreatment peripheral blood TCR clonality below the median was associated with improved PFS (n = 29, log-rank p = 0.048) and OS (n = 29, log-rank p = 0.011). Patients with DCB also demonstrated more substantial expansion of tumor-associated TCR clones in the peripheral blood 3 weeks after starting treatment (n = 22, Mann-Whitney p = 0.022). The combination of high pretreatment peripheral blood TCR clonality with elevated PD-L1 IC staining in tumor tissue was strongly associated with poor clinical outcomes (n = 10, hazard ratio (HR) (mean) = 89.88, HR (median) = 23.41, 95% CI [2.43, 506.94], p(HR > 1) = 0.0014). Marked variations in mutation loads were seen with different somatic variant calling methodologies, which, in turn, impacted associations with clinical outcomes. Missense mutation load, predicted neoantigen load, and expressed neoantigen load did not demonstrate significant association with DCB (n = 25, Mann-Whitney p = 0.22, n = 25, Mann-Whitney p = 0.55, and n = 25, Mann-Whitney p = 0.29, respectively). Instead, we found evidence of time-varying effects of somatic mutation load on PFS in this cohort (n = 25, p = 0.044). A limitation of our study is its small sample size (n = 29), a subset of the patients treated on IMvigor 210 (NCT02108652). Given the number of exploratory analyses performed, we intend for these results to be hypothesis-generating. These results demonstrate the complex nature of immune response to checkpoint blockade and the compelling need for greater interrogation and data integration of both host and tumor factors. Incorporating these variables in prospective studies will facilitate identification and treatment of resistant patients.

Impact of Diabetic Complications on Balance and Falls: Contribution of the Vestibular System

PubMed Central

Lin, James; Staecker, Hinrich; Whitney, Susan L.; Kluding, Patricia M.

2016-01-01

Diabetes causes many complications, including retinopathy and peripheral neuropathy, which are well understood as contributing to gait instability and falls. A less understood complication of diabetes is the effect on the vestibular system. The vestibular system contributes significantly to balance in static and dynamic conditions by providing spatially orienting information. It is noteworthy that diabetes has been reported to affect vestibular function in both animal and clinical studies. Pathophysiological changes in peripheral and central vestibular structures due to diabetes have been noted. Vestibular dysfunction is associated with impaired balance and a higher risk of falls. As the prevalence of diabetes increases, so does the potential for falls due to diabetic complications. The purpose of this perspective article is to present evidence on the pathophysiology of diabetes-related complications and their influence on balance and falls, with specific attention to emerging evidence of vestibular dysfunction due to diabetes. Understanding this relationship may be useful for screening (by physical therapists) for possible vestibular dysfunction in people with diabetes and for further developing and testing the efficacy of interventions to reduce falls in this population. PMID:26251477

[Regeneration and repair of peripheral nerves: clinical implications in facial paralysis surgery].

PubMed

Hontanilla, B; Vidal, A

2000-01-01

Peripheral nerve lesions are one of the most frequent causes of chronic incapacity. Upper or lower limb palsies due to brachial or lumbar plexus injuries, facial paralysis and nerve lesions caused by systemic diseases are one of the major goals of plastic and reconstructive surgery. However, the poor results obtained in repaired peripheral nerves during the Second World War lead to a pessimist vision of peripheral nerve repair. Nevertheless, a well understanding of microsurgical principles in reconstruction and molecular biology of nerve regeneration have improved the clinical results. Thus, although the results obtained are quite far from perfect, these procedures give to patients a hope in the recuperation of their lesions and then on function. Technical aspects in nerve repair are well established; the next step is to manipulate the biology. In this article we will comment the biological processes which appear in peripheral nerve regeneration, we will establish the main concepts on peripheral nerve repair applied in facial paralysis cases and, finally, we will proportionate some ideas about how clinical practice could be affected by manipulation of the peripheral nerve biology.

The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the Neuromodulation Appropriateness Consensus Committee.

PubMed

Deer, Timothy R; Mekhail, Nagy; Provenzano, David; Pope, Jason; Krames, Elliot; Leong, Michael; Levy, Robert M; Abejon, David; Buchser, Eric; Burton, Allen; Buvanendran, Asokumar; Candido, Kenneth; Caraway, David; Cousins, Michael; DeJongste, Michael; Diwan, Sudhir; Eldabe, Sam; Gatzinsky, Kliment; Foreman, Robert D; Hayek, Salim; Kim, Philip; Kinfe, Thomas; Kloth, David; Kumar, Krishna; Rizvi, Syed; Lad, Shivanand P; Liem, Liong; Linderoth, Bengt; Mackey, Sean; McDowell, Gladstone; McRoberts, Porter; Poree, Lawrence; Prager, Joshua; Raso, Lou; Rauck, Richard; Russo, Marc; Simpson, Brian; Slavin, Konstantin; Staats, Peter; Stanton-Hicks, Michael; Verrills, Paul; Wellington, Joshua; Williams, Kayode; North, Richard

2014-08-01

The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications. The NACC used literature reviews, expert opinion, clinical experience, and individual research. Authors consulted the Practice Parameters for the Use of Spinal Cord Stimulation in the Treatment of Neuropathic Pain (2006), systematic reviews (1984 to 2013), and prospective and randomized controlled trials (2005 to 2013) identified through PubMed, EMBASE, and Google Scholar. Neurostimulation is relatively safe because of its minimally invasive and reversible characteristics. Comparison with medical management is difficult, as patients considered for neurostimulation have failed conservative management. Unlike alternative therapies, neurostimulation is not associated with medication-related side effects and has enduring effect. Device-related complications are not uncommon; however, the incidence is becoming less frequent as technology progresses and surgical skills improve. Randomized controlled studies support the efficacy of spinal cord stimulation in treating failed back surgery syndrome and complex regional pain syndrome. Similar studies of neurostimulation for peripheral neuropathic pain, postamputation pain, postherpetic neuralgia, and other causes of nerve injury are needed. International guidelines recommend spinal cord stimulation to treat refractory angina; other indications, such as congestive heart failure, are being investigated. Appropriate neurostimulation is safe and effective in some chronic pain conditions. Technological refinements and clinical evidence will continue to expand its use. The NACC seeks to facilitate the efficacy and safety of neurostimulation. © 2014 International Neuromodulation Society.

Phenotypic characterization of X-linked retinoschisis: Clinical, electroretinography, and optical coherence tomography variables

PubMed Central

Neriyanuri, Srividya; Dhandayuthapani, Sudha; Arunachalam, Jayamuruga Pandian; Raman, Rajiv

2016-01-01

Aims: To study the phenotypic characteristics of X-linked retinoschisis (XLRS) and report the clinical, electroretinogram (ERG), and optical coherence tomography (OCT) variables in Indian eyes. Design: A retrospective study. Materials and Methods: Medical records of 21 patients with retinoschisis who were genetically confirmed to have RS1 mutation were reviewed. The phenotype characterization included the age of onset, best-corrected visual acuity, refractive error, fundus findings, OCT, and ERG. Statistical Analysis Used: Data from both the eyes were used for analysis. A P < 0.05 was set as statistical significance. Data were not normally distributed (P < 0.05, Shapiro wilk); hence, nonparametric tests were used for statistical analysis. Results: All were males whose mean age of presentation was 9 years. Visual acuity was moderately impaired (median 0.6 logMAR, interquartile range: 0.47, 1) in these eyes with a hyperopic refractive error of median +1.75 Ds (interquartile range: +0.50 Ds, +4.25 Ds). About 54.7% of the eyes had both foveal and peripheral schisis, isolated foveal schisis was seen in 28.5% of the eyes, and schisis with retinal detachment was seen in 16.6% of the eyes. The inner nuclear layer was found to be commonly involved in the schisis, followed by outer nuclear and plexiform layers as evident on OCT. On ERG, a- and b-wave amplitudes were significantly reduced in eyes with foveal and peripheral schisis when compared to the eyes with only foveal schisis (P < 0.05). Conclusions: XLRS has phenotypic heterogeneity as evident on OCT, ERG, and clinical findings. PMID:27609164

The validity of upper-limb neurodynamic tests for detecting peripheral neuropathic pain.

PubMed

Nee, Robert J; Jull, Gwendolen A; Vicenzino, Bill; Coppieters, Michel W

2012-05-01

The validity of upper-limb neurodynamic tests (ULNTs) for detecting peripheral neuropathic pain (PNP) was assessed by reviewing the evidence on plausibility, the definition of a positive test, reliability, and concurrent validity. Evidence was identified by a structured search for peer-reviewed articles published in English before May 2011. The quality of concurrent validity studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool, where appropriate. Biomechanical and experimental pain data support the plausibility of ULNTs. Evidence suggests that a positive ULNT should at least partially reproduce the patient's symptoms and that structural differentiation should change these symptoms. Data indicate that this definition of a positive ULNT is reliable when used clinically. Limited evidence suggests that the median nerve test, but not the radial nerve test, helps determine whether a patient has cervical radiculopathy. The median nerve test does not help diagnose carpal tunnel syndrome. These findings should be interpreted cautiously, because diagnostic accuracy might have been distorted by the investigators' definitions of a positive ULNT. Furthermore, patients with PNP who presented with increased nerve mechanosensitivity rather than conduction loss might have been incorrectly classified by electrophysiological reference standards as not having PNP. The only evidence for concurrent validity of the ulnar nerve test was a case study on cubital tunnel syndrome. We recommend that researchers develop more comprehensive reference standards for PNP to accurately assess the concurrent validity of ULNTs and continue investigating the predictive validity of ULNTs for prognosis or treatment response.

Clinical effectiveness of garlic (Allium sativum).

PubMed

Pittler, Max H; Ernst, Edzard

2007-11-01

The objective of this review is to update and assess the clinical evidence based on rigorous trials of the effectiveness of garlic (A. sativum). Systematic searches were carried out in Medline, Embase, Amed, the Cochrane Database of Systematic Reviews, Natural Standard, and the Natural Medicines Comprehensive Database (search date December 2006). Our own files, the bibliographies of relevant papers and the contents pages of all issues of the review journal FACT were searched for further studies. No language restrictions were imposed. To be included, trials were required to state that they were randomized and double blind. Systematic reviews and meta-analyses of garlic were included if based on the results of randomized, double-blind trials. The literature searches identified six relevant systematic reviews and meta-analysis and double-blind randomized trials (RCT) that were published subsequently. These relate to cancer, common cold, hypercholesterolemia, hypertension, peripheral arterial disease and pre-eclampsia. The evidence based on rigorous clinical trials of garlic is not convincing. For hypercholesterolemia, the reported effects are small and may therefore not be of clinical relevance. For reducing blood pressure, few studies are available and the reported effects are too small to be clinically meaningful. For all other conditions not enough data are available for clinical recommendations.

A double blind, placebo controlled, phase II randomised cross-over trial investigating the use of duloxetine for the treatment of chemotherapy-induced peripheral neuropathy.

PubMed

Battaglini, Eva; Park, Susanna B; Barnes, Elizabeth H; Goldstein, David

2018-04-20

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of cancer treatment, potentially leading to early cessation of chemotherapy, enduring symptoms and long-lasting disability. Evidence from preclinical and clinical studies suggests that duloxetine, a serotonin-noradrenaline reuptake inhibitor, may be effective in the symptomatic treatment of CIPN. This double blind, placebo controlled, phase II randomised cross-over trial aims to determine whether treatment with duloxetine results in a reduction in chronic neuropathic symptoms experienced as a result of neurotoxic chemotherapy treatment. Participants who have received neurotoxic chemotherapy and experience daily symptoms as a consequence of peripheral neuropathy will be randomly allocated to control or experimental group with a 1:1 allocation, stratified by chemotherapy type. The primary endpoint will be patient-reported CIPN symptoms, as assessed via the FACT/GOG-Ntx. As a secondary objective, the trial will investigate whether duloxetine improves neurophysiological parameters and functional status in patients who have received neurotoxic chemotherapy treatment. This trial will investigate the effectiveness of duloxetine in reducing neuropathic symptoms following chemotherapy treatment, and aims to provide insight into the mechanisms underlying the symptomatic relief that duloxetine may provide. These results will be informative in advancing clinical knowledge regarding the treatment of CIPN. Copyright © 2018 Elsevier Inc. All rights reserved.

Crusted scabies is associated with increased IL-17 secretion by skin T cells.

PubMed

Liu, X; Walton, S F; Murray, H C; King, M; Kelly, A; Holt, D C; Currie, B J; McCarthy, J S; Mounsey, K E

2014-11-01

Scabies is an ectoparasitic infestation by the mite Sarcoptes scabiei. Although commonly self-limiting, a fraction of patients develop severely debilitating crusted scabies. The immune mechanisms underlying the development of crusted scabies are unclear, and undertaking longitudinal infection studies in humans is difficult. We utilized a porcine model to compare cellular immune responses in peripheral blood and skin of pigs with different clinical manifestations of scabies (n = 12), and in uninfected controls (n = 6). Although clinical symptoms were not evident until at least 4 weeks post-infestation, the numbers of peripheral IFNγ-secreting CD4(+) T cells and γδ T cells increased in infected pigs from week 1 post-infestation. γδ T cells remained increased in the blood at week 15 post-infestation. At week 15, skin cell infiltrates from pigs with crusted scabies had significantly higher CD8(+) T cell, γδ T cell and IL-17(+) cell numbers than those with ordinary scabies. Peripheral IL-17 levels were not increased, suggesting that localized skin IL-17-secreting T cells may play a critical role in the pathogenesis of crusted scabies development. Given the potential of anti-IL-17 immunotherapy demonstrated for other inflammatory skin diseases, this study may provide a novel therapeutic avenue for patients with recurrent crusted scabies. © 2014 John Wiley & Sons Ltd.

Inflammatory Markers in the Staging of Bipolar Disorder: A Systematic Review of the Literature.

PubMed

Castaño-Ramírez, Oscar Mauricio; Sepúlveda-Arias, Juan C; Duica, Kelly; Díaz Zuluaga, Ana M; Vargas, Cristian; López-Jaramillo, Carlos

Previous studies suggest that inflammatory molecules play an important role in the pathophysiology of Bipolar Disorder (BD). The evidence suggests that BD may present a progressive course. Therefore there are theories that postulate the relationship between progression and stages of the disease with distinct peripheral biomarkers. The aim of this study was to carry out a systematic review of the literature of studies about the association between peripheral inflammatory markers and clinical variables related with staging in BD patients. We conducted a systematic review using electronic databases: PubMed, SciELO, LiLACS and PsycINFO. Keywords were divided into inflammatory markers and, BD and staging. Studies involving euthymic BD patients, studies evaluating peripheral biomarkers and studies correlating these with clinical variables related to neuroprogression or stage of BD were included. We present and discuss the methods and findings of ten articles. The inflammatory markers were measured with different techniques and show some contradictories results. The TNF superfamily and inflammatory cytokines may have a relationship with the neuroprogression of the disease. This study suggests that TNF and ILs could play a role in neuroprogression. However, longitudinal studies are needed to clarify the relationship between factors associated with neuroprogression. Copyright © 2017 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Neurofilament light chain as disease biomarker in a rodent model of chemotherapy induced peripheral neuropathy.

PubMed

Meregalli, Cristina; Fumagalli, Giulia; Alberti, Paola; Canta, Annalisa; Carozzi, Valentina Alda; Chiorazzi, Alessia; Monza, Laura; Pozzi, Eleonora; Sandelius, Åsa; Blennow, Kaj; Zetterberg, Henrik; Marmiroli, Paola; Cavaletti, Guido

2018-06-13

The objective of this study is to test the feasibility of using serum neurofilament light chain (NfL) as a disease biomarker in Chemotherapy Induced Peripheral Neuropathy (CIPN) since this easy accessible biological test may have a large impact on clinical management and safety of cancer patients. We performed this preclinical study using a well-characterized rat model based on repeated administration of the cytostatic drug vincristine (VCR, 0.2 mg/kg intravenously via the tail vein once/week for 4 times). Serial NfL serum concentration measured using the in-house Simoa NfL assay and peripheral neuropathy onset was measured by sensory and motor nerve conduction studies. Serum NfL measure in untreated and VCR-treated rats demonstrated a steady, and significant increase during the course of VCR administration, with a final 4-fold increase with respect to controls (p < .001) when sign of axonopathy and loss of intraepidermal nerve fibers were clearly evident and verified by behavioral, neurophysiological and pathological examination. This simple monitoring approach based on serum NfL concentration measures may be easily translated to clinical practice and should be considered as a putative marker of CIPN severity in a typical oncology outpatient setting. Further studies are needed to validate it's utility in cancer patients treated with different neurotoxic drugs. Copyright © 2017. Published by Elsevier Inc.

Effect of Q211 and K222 PRNP Polymorphic Variants in the Susceptibility of Goats to Oral Infection With Goat Bovine Spongiform Encephalopathy.

PubMed

Aguilar-Calvo, Patricia; Fast, Christine; Tauscher, Kerstin; Espinosa, Juan-Carlos; Groschup, Martin H; Nadeem, Muhammad; Goldmann, Wilfred; Langeveld, Jan; Bossers, Alex; Andreoletti, Olivier; Torres, Juan-María

2015-08-15

The prion protein-encoding gene (PRNP) is one of the major determinants for scrapie occurrence in sheep and goats. However, its effect on bovine spongiform encephalopathy (BSE) transmission to goats is not clear. Goats harboring wild-type, R/Q211 or Q/K222 PRNP genotypes were orally inoculated with a goat-BSE isolate to assess their relative susceptibility to BSE infection. Goats were killed at different time points during the incubation period and after the onset of clinical signs, and their brains as well as several peripheral tissues were analyzed for the accumulation of pathological prion protein (PrP(Sc)) and prion infectivity by mouse bioassay. R/Q211 goats displayed delayed clinical signs compared with wild-type goats. Deposits of PrP(Sc) were detected only in brain, whereas infectivity was present in peripheral tissues too. In contrast, none of the Q/K222 goats showed any evidence of clinical prion disease. No PrP(Sc) accumulation was observed in their brains or peripheral tissues, but very low infectivity was detected in some tissues very long after inoculation (44-45 months). These results demonstrate that transmission of goat BSE is genotype dependent, and they highlight the pivotal protective effect of the K222 PRNP variant in the oral susceptibility of goats to BSE. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Prevalence and features of peripheral neuropathy in Parkinson's disease patients under different therapeutic regimens.

PubMed

Mancini, F; Comi, C; Oggioni, G D; Pacchetti, C; Calandrella, D; Coletti Moja, M; Riboldazzi, G; Tunesi, S; Dal Fante, M; Manfredi, L; Lacerenza, M; Cantello, R; Antonini, A

2014-01-01

Recent reports suggest increased frequency of peripheral neuropathy (PN) in Parkinson's disease (PD) patients on levodopa compared with age-matched controls particularly during continuous levodopa delivery by intestinal infusion (CLDII). The aim of this study is to compare frequency, clinical features, and outcome of PN in PD patients undergoing different therapeutic regimens. Three groups of consecutive PD patients, 50 on intestinal levodopa (CLDII), 50 on oral levodopa (O-LD) and 50 on other dopaminergic treatment (ODT), were enrolled in this study to assess frequency of PN using clinical and neurophysiological parameters. A biochemical study of all PN patients was performed. Frequency of PN of no evident cause was 28% in CLDII, 20% in O-LD, and 6% in ODT patients. Clinically, 71% of CLDII patients and all O-LD and ODT PN patients displayed a subacute sensory PN. In contrast, 29% of CLDII patients presented acute motor PN. Levodopa daily dose, vitamin B12 (VB12) and homocysteine (hcy) levels differed significantly in patients with PN compared to patients without PN. Our findings support the relationship between levodopa and PN and confirm that an imbalance in VB12/hcy may be a key pathogenic factor. We suggest two different, possibly overlapping mechanisms of PN in patients on CDLII: axonal degeneration due to vitamin deficiency and inflammatory damage. Whether inflammatory damage is triggered by vitamin deficiency and/or by modifications in the intestinal micro-environment should be further explored. Proper vitamin supplementation may prevent peripheral damage in most cases. Copyright © 2013 Elsevier Ltd. All rights reserved.

Randomized crossover clinical trial of real and sham peripheral prism glasses for hemianopia.

PubMed

Bowers, Alex R; Keeney, Karen; Peli, Eli

2014-02-01

There is a major lack of randomized controlled clinical trials evaluating the efficacy of prismatic treatments for hemianopia. Evidence for their effectiveness is mostly based on anecdotal case reports and open-label evaluations without a control condition. To evaluate the efficacy of real relative to sham peripheral prism glasses for patients with complete homonymous hemianopia. Double-masked, randomized crossover trial at 13 study sites, including the Peli laboratory at Schepens Eye Research Institute, 11 vision rehabilitation clinics in the United States, and 1 in the United Kingdom. Patients were 18 years or older with complete homonymous hemianopia for at least 3 months and without visual neglect or significant cognitive decline. Patients were allocated by minimization into 2 groups. One group received real (57-prism diopter) oblique and sham (<5-prism diopter) horizontal prisms; the other received real horizontal and sham oblique, in counterbalanced order. Each crossover period was 4 weeks. The primary outcome was the overall difference, across the 2 periods of the crossover, between the proportion of participants who wanted to continue with (said yes to) real prisms and the proportion who said yes to sham prisms. The secondary outcome was the difference in perceived mobility improvement between real and sham prisms. Of 73 patients randomized, 61 completed the crossover. A significantly higher proportion said yes to real than sham prisms (64% vs 36%; odds ratio, 5.3; 95% CI, 1.8-21.0). Participants who continued wear after 6 months reported greater improvement in mobility with real than sham prisms at crossover end (P = .002); participants who discontinued wear reported no difference. Real peripheral prism glasses were more helpful for obstacle avoidance when walking than sham glasses, with no differences between the horizontal and oblique designs. Peripheral prism glasses provide a simple and inexpensive mobility rehabilitation intervention for hemianopia. clinicaltrials.gov Identifier: NCT00494676.

Adopting new technologies in stroke rehabilitation: the influence of the US health care system.

PubMed

Stein, J

2009-06-01

Stroke rehabilitation is entering a new era of technological innovation, including the development of robotic aids for therapy, peripheral electrical stimulation devices, and brain stimulation systems. These technologies have the potential to significantly improve the efficiency and efficacy of stroke rehabilitation. The United States health care system creates both opportunities for new technologies to be created and adopted, as well as important barriers. Inadequate support of clinical trials of the efficacy of new non-invasive devices is a particular concern for practitioners seeking to determine if new devices are clinically useful. Government support of clinical trials of efficacy, coupled with reform of FDA approval processes for novel therapies, is needed to create an evidence-based approach to improving stroke rehabilitation.

The Importance of Rare Subtypes in Diagnosis and Treatment of Peripheral Neuropathy: A Review.

PubMed

Callaghan, Brian C; Price, Raymond S; Chen, Kevin S; Feldman, Eva L

2015-12-01

Peripheral neuropathy is a prevalent condition that usually warrants a thorough history and examination but has limited diagnostic evaluation. However, rare localizations of peripheral neuropathy often require more extensive diagnostic testing and different treatments. To describe rare localizations of peripheral neuropathy, including the appropriate diagnostic evaluation and available treatments. References were identified from PubMed searches conducted on May 29, 2015, with an emphasis on systematic reviews and randomized clinical trials. Articles were also identified through the use of the authors' own files. Search terms included common rare neuropathy localizations and their causes, as well as epidemiology, pathophysiology, diagnosis, and treatment. Diffuse, nonlength-dependent neuropathies, multiple mononeuropathies, polyradiculopathies, plexopathies, and radiculoplexus neuropathies are rare peripheral neuropathy localizations that often require extensive diagnostic testing. Atypical neuropathy features, such as acute/subacute onset, asymmetry, and/or motor predominant signs, are frequently present. The most common diffuse, nonlength-dependent neuropathies are Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and amyotrophic lateral sclerosis. Effective disease-modifying therapies exist for many diffuse, nonlength-dependent neuropathies including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and some paraprotein-associated demyelinating neuropathies. Vasculitic neuropathy (multiple mononeuropathy) also has efficacious treatment options, but definitive evidence of a treatment effect for IgM anti-MAG neuropathy and diabetic amyotrophy (radiculoplexus neuropathy) is lacking. Recognition of rare localizations of peripheral neuropathy is essential given the implications for diagnostic testing and treatment. Electrodiagnostic studies are an important early step in the diagnostic evaluation and provide information on the localization and pathophysiology of nerve injury.

Review of drug treatment of oral submucous fibrosis.

PubMed

Chole, Revant H; Gondivkar, Shailesh M; Gadbail, Amol R; Balsaraf, Swati; Chaudhary, Sudesh; Dhore, Snehal V; Ghonmode, Sumeet; Balwani, Satish; Mankar, Mugdha; Tiwari, Manish; Parikh, Rima V

2012-05-01

This study undertook a review of the literature on drug treatment of oral submucous fibrosis. An electronic search was carried out for articles published between January 1960 to November 2011. Studies with high level of evidence were included. The levels of evidence of the articles were classified after the guidelines of the Oxford Centre for Evidence-Based Medicine. The main outcome measures used were improvement in oral ulceration, burning sensation, blanching and trismus. Only 13 publications showed a high level of evidence (3 randomized controlled trials and 10 clinical trials/controlled clinical trials), with a total of 1157 patients. Drugs like steroids, hyaluronidase, human placenta extracts, chymotrypsin and collagenase, pentoxifylline, nylidrin hydrochloride, iron and multivitamin supplements including lycopene, have been used. Only systemic agents were associated with few adverse effects like gastritis, gastric irritation and peripheral flushing with pentoxifylline, and flushingly warm skin with nylidrin hydrochloride; all other side-effects were mild and mainly local. Few studies with high levels of evidence were found. The drug treatment that is currently available for oral submucous fibrosis is clearly inadequate. There is a need for high-quality randomized controlled trials with carefully selected and standardized outcome measures. Copyright © 2011 Elsevier Ltd. All rights reserved.

Intraplantar injection of bergamot essential oil induces peripheral antinociception mediated by opioid mechanism.

PubMed

Sakurada, Tsukasa; Mizoguchi, Hirokazu; Kuwahata, Hikari; Katsuyama, Soh; Komatsu, Takaaki; Morrone, Luigi Antonio; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Sakurada, Shinobu

2011-01-01

This study investigated the effect of bergamot essential oil (BEO) containing linalool and linalyl acetate as major volatile components in the capsaicin test. The intraplantar injection of capsaicin (1.6 μg) produced a short-lived licking/biting response toward the injected paw. The nociceptive behavioral response evoked by capsaicin was inhibited dose-dependently by intraplantar injection of BEO. Both linalool and linalyl acetate, injected into the hindpaw, showed a significant reduction of nociceptive response, which was much more potent than BEO. Intraperitoneal (i.p.) and intraplantar pretreatment with naloxone hydrochloride, an opioid receptor antagonist, significantly reversed BEO- and linalool-induced antinociception. Pretreatment with naloxone methiodide, a peripherally acting μ-opioid receptor preferring antagonist, resulted in a significant antagonizing effect on antinociception induced by BEO and linalool. Antinociception induced by i.p. or intrathecal morphine was enhanced by the combined injection of BEO or linalool. The enhanced effect of combination of BEO or linalool with morphine was antagonized by pretreatment with naloxone hydrochloride. Our results provide evidence for the involvement of peripheral opioids, in the antinociception induced by BEO and linalool. Combined administration of BEO or linalool acting at the peripheral site, and morphine may be a promising approach in the treatment of clinical pain. Copyright © 2010 Elsevier Inc. All rights reserved.

Transient myeloproliferative disease of the newborn: case report with placental, cytogenetic, and flow cytometric findings.

PubMed

de Tar, M W; Dittman, W; Gilbert, J

2000-03-01

Transient myeloproliferative disease (TMD) of the newborn is a rare hematologic abnormality associated with trisomy 21. It is frequently difficult to distinguish the disorder from true congenital leukemia (TCL). Unlike leukemia, which has a clinically aggressive course, TMD generally resolves within weeks to months. We present a case of TMD of the newborn diagnosed on the basis of peripheral blood studies and describe the pertinent pathological findings within the placenta. Flow cytometric analysis of the blasts in the peripheral blood showed phenotypic heterogeneity with features consistent with megakaryocytic differentiation. Cytogenetic studies showed trisomy 21 within the blastic cells. The placenta showed villous dysmaturity with associated chorangiosis and prominent intravascular aggregates of primitive-appearing cells with focal, early vascular wall invasion. The neonate recovered fully and shows no evidence of disease at 2 years of age.

High viral load in lymph nodes and latent human immunodeficiency virus (HIV) in peripheral blood cells of HIV-1-infected chimpanzees.

PubMed Central

Saksela, K; Muchmore, E; Girard, M; Fultz, P; Baltimore, D

1993-01-01

We have examined human immunodeficiency virus type 1 (HIV-1) infection in chimpanzees by analyzing HIV-1 DNA and RNA in lymph nodes and peripheral mononuclear cells (PBMCs). Like certain asymptomatic HIV-infected persons, these chimpanzees had no detectable viral replication in their PBMCs. However, viral replication and a high viral load were observed in the lymphatic tissue. Despite the absence of viral replication in PBMCs, 1/1,000 to 1/10,000 of the PBMCs contained HIV-1 proviral DNA, and HIV transcription could be rapidly induced in these cells in vitro. These results provide direct evidence of cellular latency of HIV in vivo and suggest that HIV infection in chimpanzees may be a useful model for clinical latency of HIV infection in humans. Images PMID:8230463

[Involvement of the peripheral nervous system in systemic connective tissue diseases: report on clinical cases].

PubMed

Kujawska-Danecka, Hanna; Masiak, Anna; Smoleńska, Zaneta; Zdrojewski, Zbigniew

2011-01-01

The peripheral nervous system is usually involved in the majority of systemic connective tissue diseases, particularly in systemic lupus erythematosus, Sjögren's syndrome, vasculitis and systemic sclerosis. The pathogenesis of lesions in the peripheral nervous system associated with the autoimmune process is complex and it appears that two mechanisms, immunological and ischemic, are of greatest importance. Structures of the nervous system may be damaged by several autoantibodies (e.g. antineuronal, anti-nerve growth factor, anti-neurotrophins), by cytotoxic effects ofproinflammatory cytokines and by activated cells of the immune system. Local ischemia and hypoxia of neurons caused by inflammation of vasa nervosum represents the second significant mechanism leading to damage of nerve fibres in the peripheral nervous system. We present 3 cases with involvement of the peripheral nervous system as a dominant feature in the clinical picture of systemic connective tissue diseases. Clinical conditions in which the peripheral nervous system is involved include peripheral sensory and sensorimotor polyneuropathy, mononeuropathies, cranial neuropathies, acute inflammatory demyelinating polyneuropathy (Guillian-Barré syndrome), chronic inflammatory demyelinating polyneuropathy, plexopathy, myasthenia gravis, and dysfunctions of the autonomic nervous system. The diagnosis is based on clinical symptoms reported by the patient and disclosed during neurologic examination. The importance of electrophysiologic tests is advocated. Selection of treatment depends on the patient's clinical condition, as well as on the clinical form and type of disease. Treatment relies principally on glucocorticosteroids, intravenous immunoglobulins, cyclophosphamide, and other immunosuppressive drugs. Plasmapheresis and rituximab are administered in severe cases. Rehabilitation of the patient appears to be an important element of therapy. Cases with neurologic symptoms as the first and often the sole manifestation of systemic connective tissue disease are particularly problematic requiring a multidimensional approach; their process of diagnosis and treatment is usually long.

Registry Assessment of Peripheral Interventional Devices (RAPID): Registry assessment of peripheral interventional devices core data elements.

PubMed

Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert A; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L

2018-02-01

The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible. Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators. Copyright © 2017 Society for Vascular Surgery. All rights reserved.

Incidence and risk of peripheral neuropathy with nab-paclitaxel in patients with cancer: a meta-analysis.

PubMed

Peng, L; Bu, Z; Ye, X; Zhou, Y; Zhao, Q

2017-09-01

Nab-paclitaxel, a Cremophor EL-free formulation of paclitaxel, is used to treat various malignancies. Peripheral neuropathy is one of its major toxicities, although the overall incidence remains unclear. We performed a meta-analysis to calculate the incidence of peripheral neuropathy in cancer patients treated with nab-paclitaxel and to compare the relative risk (RR) with conventional taxanes. The electronic databases were searched for relevant clinical trials. Eligible studies included phase II and III prospective clinical trials of cancer patients treated with nab-paclitaxel with toxicity profile on peripheral neuropathy. Statistical analyses were done to calculate summary incidences, RRs and 95% confidence intervals (CI), using fixed-effects or random-effects models based on the heterogeneity of the included studies. Nineteen trials were selected for the meta-analysis, yielding a total of 2878 cancer patients. The overall incidences of peripheral neuropathy (all-grade) was 51.0% (95% CI: 45.1-57.6%), and that of high-grade peripheral neuropathy was 12.4% (9.8-15.7%). The RRs of peripheral neuropathy of nab-paclitaxel compared to taxanes were not increased for all-grade and high-grade peripheral neuropathy. Nab-paclitaxel is associated with an increased risk of developing peripheral neuropathy. Future clinical studies are still needed to investigate the risk reduction and possible use of nab-paclitaxel. © 2015 John Wiley & Sons Ltd.

Theory underlying the peripheral vision horizon device

NASA Technical Reports Server (NTRS)

Money, K. E.

1984-01-01

Peripheral Vision Horizon Device (PVHD) theory states that the likelihood of pilot disorientation in flight is reduced by providing an artificial horizon that provides orientation information to peripheral vision. In considering the validity of the theory, three areas are explored: the use of an artificial horizon device over some other flight instrument; the use of peripheral vision over foveal vision; and the evidence that peripheral vision is well suited to the processing of orientation information.

A meta-analysis of peripheral blood nerve growth factor levels in patients with schizophrenia.

PubMed

Qin, X-Y; Wu, H-T; Cao, C; Loh, Y P; Cheng, Y

2017-09-01

Neurotrophins particularly brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are crucial modulators in the neurodevelopment and maintenance of central and peripheral nervous systems. Neurotrophin hypothesis of schizophrenia (SCZ) postulated that the changes in the brains of SCZ patients are the result of disturbances of developing processes involving neurotrophic factors. This hypothesis was mainly supported by the abnormal regulation of BDNF in SCZ, especially the decreased peripheral blood BDNF levels in SCZ patients validated by several meta-analyses. However, the regulation of NGF in SCZ remains unclear because of the inconsistent findings from the clinical studies. Therefore, we undertook, to the best of our knowledge, the first systematic review with a meta-analysis to quantitatively summarize the peripheral blood NGF data in SCZ patients compared with healthy control (HC) subjects. A systematic search of Pubmed, PsycINFO and Web of Science identified 13 articles encompassing a sample of 1693 individuals for the meta-analysis. Random-effects meta-analysis showed that patients with SCZ had significantly decreased peripheral blood levels of NGF when compared with the HC subjects (Hedges's g=-0.633, 95% confidence interval (CI)=-0.948 to -0.318, P<0.001). Subgroup analyses revealed reduced NGF levels both in serum (Hedges's g=-0.671, 95% CI=-1.259 to -0.084, P=0.025) and plasma (Hedges's g=-0.621, 95% CI=-0.980 to -0.261, P<0.001) of the patients, and in drug-free (Hedges's g=-0.670, 95% CI=-1.118 to -0.222, P=0.003) and medicated (Hedges's g=-0.357, 95% CI=-0.592 to -0.123, P=0.003) patients with SCZ. Furthermore, meta-regression analyses showed that age, gender and sample size had no moderating effects on the outcome of the meta-analysis, whereas disease severity might be a confounding factor for the meta-analysis. These results demonstrated that patients with SCZ are accompanied by the decreased peripheral blood NGF levels, strengthening the clinical evidence of an abnormal neurotrophin profile in the patients with SCZ.

Symptomatic and Electrodiagnostic Features of Peripheral Neuropathy in Scleroderma.

PubMed

Paik, Julie J; Mammen, Andrew L; Wigley, Fredrick M; Shah, Ami A; Hummers, Laura K; Polydefkis, Michael

2016-08-01

To determine the prevalence of peripheral neuropathy in scleroderma. The prevalence of length-dependent peripheral neuropathy was rigorously assessed using signs and symptoms of neuropathy derived from the Total Neuropathy Score (TNS), and standardized nerve conduction study (NCS). All subjects underwent TNS and NCS. Those who were symptomatic or had NCS evidence of peripheral neuropathy underwent laboratory evaluation for secondary causes of neuropathy. A total of 130 subjects were approached for participation and 60 enrolled. Of the 60 subjects, 50 (83.3%) were female and 37 (61.7%) were of the limited cutaneous subtype. The mean ± SD age was 55 ± 11.1 years, and mean ± SD disease duration was 15.3 ± 10.1 years. A total of 17 of 60 (28%) had evidence of a peripheral neuropathy as defined by the presence of neuropathic symptoms on the TNS (12 of 60) and/or electrophysiologic evidence of neuropathy (5 subjects with neuropathic symptoms and 5 without neuropathic symptoms). Subjects with neuropathy were more likely to be male (60% versus 40%; P = 0.02), African American (41% versus 4.6%; P = 0.001), have diabetes mellitus (17.7% versus 0%; P = 0.02), have limited cutaneous scleroderma (82.3% versus 53.5%; P = 0.04), and have anti-U1 RNP antibodies (23.5% versus 0%; P = 0.009) than those without neuropathy. A potential nonscleroderma etiology for the peripheral neuropathy such as diabetes mellitus was found in 82.3% (14 of 17) of subjects with neuropathy. While symptoms or objective evidence of peripheral neuropathy are common among patients with scleroderma, the cause may often be attributed to comorbid nonscleroderma-related conditions. © 2016, American College of Rheumatology.

Extraneural findings during peripheral nerve ultrasound: Prevalence and further assessment.

PubMed

Bignotti, Bianca; Zaottini, Federico; Airaldi, Sonia; Martinoli, Carlo; Tagliafico, Alberto

2018-01-01

In this study we evaluated the frequency and further assessment of extraneural findings encountered during peripheral nerve ultrasound (US). Our retrospective review identified 278 peripheral nerve US examinations of 229 patients performed between December 2014 and December 2015. Reports were reviewed to assess the number of studies without peripheral nerve abnormalities and the frequency and further assessment of extraneural findings. A total of 107 peripheral nerve US examinations of 90 patients (49 men and 41 women, mean age 55 ± 16 years) did not report peripheral nerve abnormalities. Extraneural findings were observed in 24 of 107 (22.4%) studies. Fifteen of the 278 [5.4% (95% confidence interval 2.7%-8.1%)] studies led to a recommendation for additional imaging or clinical evaluation of an extraneural finding. At least 5.4% (15 of 278) of peripheral nerve US studies led to additional clinical or imaging assessment. Muscle Nerve 57: 65-69, 2018. © 2017 Wiley Periodicals, Inc.

Meta-analysis of incidence and risk of peripheral neuropathy associated with intravenous bortezomib.

PubMed

Peng, Ling; Ye, Xianghua; Zhou, Yun; Zhang, Junyan; Zhao, Qiong

2015-09-01

Bortezomib is a proteasome inhibitor which has demonstrated activity against recurrent or newly diagnosed multiple myeloma (MM) and mantle cell lymphoma. Peripheral neuropathy has been described with this agent, although the overall incidence and relative risk remain unclear. We performed a meta-analysis to calculate the incidence of peripheral neuropathy associated with the use of intravenous bortezomib in MM and lymphoma and to compare the relative risk compared with placebo. We searched PubMed, Embase, Cochrane databases, and meeting proceedings from the American Society of Clinical Oncology (ASCO) for relevant clinical trials. Eligible studies included prospective phase 2 and 3 clinical trials with toxicity profile on peripheral neuropathy associated with intravenous bortezomib in patients with MM and lymphoma. Statistical analyses were done to calculate summary incidences, relative risks (RRs), and 95 % confidence intervals (CIs), employing fixed- or random-effects models depending on the heterogeneity of the included studies. Altogether, 34 clinical trials were selected for the meta-analysis, yielding a total of 6492 patients. The incidence of peripheral neuropathy (all grades) was 33.9 % (95 % CI, 29.9-38.5 %) and that of high-grade events was 8.1 % (95 % CI, 6.9-9.4 %). The relative risks of bortezomib-induced peripheral neuropathy compared to placebo were increased for all-grade (RR = 4.89; 95 % CI, 2.52-9.51) and high-grade (RR = 4.53; 95 % CI, 2.04-10.07) peripheral neuropathy (for randomized controlled trials only). Our analysis was also stratified by different underlying diseases, and patients with lymphoma had an increased incidence of all-grade peripheral neuropathy than those with MM when treated with intravenous bortezomib. Treatment with intravenous bortezomib is associated with an increased risk of developing peripheral neuropathy.

A review of antithrombotic therapy and the rationale and design of the randomized edoxaban in patients with peripheral artery disease (ePAD) trial adding edoxaban or clopidogrel to aspirin after femoropopliteal endovascular intervention.

PubMed

Tangelder, Marco J D; Nwachuku, Chuke E; Jaff, Michael; Baumgartner, Iris; Duggal, Anil; Adams, George; Ansel, Gary; Grosso, Michael; Mercuri, Michele; Shi, Minggao; Minar, Erich; Moll, Frans L

2015-04-01

Compared with the coronary setting, knowledge about antithrombotic therapies after endovascular treatment (EVT) is inadequate in patients with peripheral artery disease (PAD). Based on a review of trials and guidelines, which is summarized in this article, there is scant evidence that antithrombotic drugs improve outcome after peripheral EVT. To address this knowledge gap, the randomized, open-label, multinational edoxaban in patients with Peripheral Artery Disease (ePAD) study (ClinicalTrials.gov identifier NCT01802775) was designed to explore the safety and efficacy of a combined regimen of antiplatelet therapy with clopidogrel and anticoagulation with edoxaban, a selective and direct factor Xa inhibitor, both combined with aspirin. As of July 2014, 203 patients (144 men; mean age 67 years) from 7 countries have been enrolled. These patients have been allocated to once-daily edoxaban [60 mg for 3 months (or 30 mg in the presence of factors associated with increased exposure)] or clopidogrel (75 mg/d for 3 months). All patients received aspirin (100 mg/d) for the 6-month duration of the study. The primary safety endpoint is major or clinically relevant nonmajor bleeding; the primary efficacy endpoint is restenosis or reocclusion at the treated segment(s) measured at 1, 3, and 6 months using duplex ultrasound scanning. All outcomes will be assessed and adjudicated centrally in a masked fashion. The ePAD study is the first of its kind to investigate a combined regimen of antiplatelet therapy and anticoagulation through factor Xa inhibition with edoxaban. © The Author(s) 2015.

Brain amyloidosis ascertainment from cognitive, imaging, and peripheral blood protein measures.

PubMed

Apostolova, Liana G; Hwang, Kristy S; Avila, David; Elashoff, David; Kohannim, Omid; Teng, Edmond; Sokolow, Sophie; Jack, Clifford R; Jagust, William J; Shaw, Leslie; Trojanowski, John Q; Weiner, Michael W; Thompson, Paul M

2015-02-17

The goal of this study was to identify a clinical biomarker signature of brain amyloidosis in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) mild cognitive impairment (MCI) cohort. We developed a multimodal biomarker classifier for predicting brain amyloidosis using cognitive, imaging, and peripheral blood protein ADNI1 MCI data. We used CSF β-amyloid 1-42 (Aβ42) ≤ 192 pg/mL as proxy measure for Pittsburgh compound B (PiB)-PET standard uptake value ratio ≥ 1.5. We trained our classifier in the subcohort with CSF Aβ42 but no PiB-PET data and tested its performance in the subcohort with PiB-PET but no CSF Aβ42 data. We also examined the utility of our biomarker signature for predicting disease progression from MCI to Alzheimer dementia. The CSF training classifier selected Mini-Mental State Examination, Trails B, Auditory Verbal Learning Test delayed recall, education, APOE genotype, interleukin 6 receptor, clusterin, and ApoE protein, and achieved leave-one-out accuracy of 85% (area under the curve [AUC] = 0.8). The PiB testing classifier achieved an AUC of 0.72, and when classifier self-tuning was allowed, AUC = 0.74. The 36-month disease-progression classifier achieved AUC = 0.75 and accuracy = 71%. Automated classifiers based on cognitive and peripheral blood protein variables can identify the presence of brain amyloidosis with a modest level of accuracy. Such methods could have implications for clinical trial design and enrollment in the near future. This study provides Class II evidence that a classification algorithm based on cognitive, imaging, and peripheral blood protein measures identifies patients with brain amyloid on PiB-PET with moderate accuracy (sensitivity 68%, specificity 78%). © 2015 American Academy of Neurology.

[Clinical features of four atypical pediatric cases of endemic typhus with pneumonia].

PubMed

Liu, Jin-rong; Xu, Bao-ping; Li, Shao-gang; Liu, Jun; Tian, Bao-lin; Zhao, Shun-ying

2013-10-01

To analyze clinical manifestations, treatment and prognosis of 4 cases with endemic typhus. The clinical data of four endemic typhus patients in prognosis were retrospectively analyzed. These four atypical cases of endemic typhus with pneumonia were treated in our department from October 2011 to March 2012. They were all male, with an age range of 15 months to 7 years. The four patients had long history, mild respiratory symptom and no improvement was found after treatment with cephalosporins. There were no evidences of bacterial, viral, or fungal infections and we thought they might have infection with other pathogen. Three were from rural areas. Routine blood tests, Weil-Felix reaction, blood smear (Giemsa staining) , and indirect immunofluorescence assay were performed. Blood smear and IFA tests showed evidences for endemic typhus. The clinical presentations were atypical, the patients had no headache, but all had fever, rash, and pneumonia of varying severity. None of the patients had a severe cough, but bronchial casts were observed in one case. Recurrent fever was reported in three cases. Physical examinations showed no eschars, but one patient had a subconjunctival hemorrhage, and one had skin scratches, cervical lymphadenopathy, pleural effusion, pericardial effusion, and cardiac dilatation. Two patients had remarkably increased peripheral blood leukocyte counts; both these patients also had high alanine aminotransferase (ALT) levels and one had a high C-reactive protein (CRP) level. Weil-Felix testing was negative or the OX19 titer was low. The peripheral blood smear (Giemsa stain) showed intracellular pathogens in all four cases. After combined therapy with doxycycline and macrolide antibiotics, all four patients recovered well. The endemic typhus children often come from rural areas. The clinical presentations were atypical, they usually have no headache, but have fever (often Periodic fever) , rash, and pneumonia of varying severity in these four cases. Combined therapy with doxycycline and macrolide antibiotics was effective in all four patients.

Modern pain neuroscience in clinical practice: applied to post-cancer, paediatric and sports-related pain.

PubMed

Malfliet, Anneleen; Leysen, Laurence; Pas, Roselien; Kuppens, Kevin; Nijs, Jo; Van Wilgen, Paul; Huysmans, Eva; Goudman, Lisa; Ickmans, Kelly

In the last decade, evidence regarding chronic pain has developed exponentially. Numerous studies show that many chronic pain populations show specific neuroplastic changes in the peripheral and central nervous system. These changes are reflected in clinical manifestations, like a generalized hypersensitivity of the somatosensory system. Besides a hypersensitivity of bottom-up nociceptive transmission, there is also evidence for top-down facilitation of pain due to malfunctioning of the endogenous descending nociceptive modulatory systems. These and other aspects of modern pain neuroscience are starting to be applied within daily clinical practice. However, currently the application of this knowledge is mostly limited to the general adult population with musculoskeletal problems, while evidence is getting stronger that also in other chronic pain populations these neuroplastic processes may contribute to the occurrence and persistence of the pain problem. Therefore, this masterclass article aims at giving an overview of the current modern pain neuroscience knowledge and its potential application in post-cancer, paediatric and sports-related pain problems. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Assessment Tools for Peripheral Neuropathy in Pediatric Oncology: A Systematic Review From the Children's Oncology Group.

PubMed

Smolik, Suzanne; Arland, Lesley; Hensley, Mary Ann; Schissel, Debra; Shepperd, Barbara; Thomas, Kristin; Rodgers, Cheryl

Peripheral neuropathy is a known side effect of several chemotherapy agents, including vinca alkaloids and platinum-based chemotherapy. Early recognition and monitoring of this side effect is an important role of the pediatric oncology nurse. There are a variety of peripheral neuropathy assessment tools currently in use, but the usefulness of these tools in identifying and grading neuropathy in children varies, and there is currently no standardized tool in place to evaluate peripheral neuropathy in pediatric oncology. A systematic review was performed to identify the peripheral neuropathy assessment tools that best evaluate the early onset and progression of peripheral neuropathy in pediatric patients receiving vincristine. Because of the limited information available in pediatric oncology, this review was extended to any pediatric patient with neuropathy. A total of 8 studies were included in the evidence synthesis. Based on available evidence, the pediatric-modified Total Neuropathy Scale (ped-m TNS) and the Total Neuropathy Score-pediatric version (TNS-PV) are recommended for the assessment of vincristine-induced peripheral neuropathy in children 6 years of age and older. In addition, several studies demonstrated that subjective symptoms alone are not adequate to assess for vincristine-induced peripheral neuropathy. Nursing assessment of peripheral neuropathy should be an integral and regular part of patient care throughout the course of chemotherapy treatment.

Abdominal pain in Irritable Bowel Syndrome: a review of putative psychological, neural and neuro-immune mechanisms.

PubMed

Elsenbruch, Sigrid

2011-03-01

Chronic abdominal pain is a common symptom of great clinical significance in several areas of medicine. In many cases no organic cause can be established resulting in the classification as functional gastrointestinal disorder. Irritable Bowel Syndrome (IBS) is the most common of these conditions and is considered an important public health problem because it can be disabling and constitutes a major social and economic burden given the lack of effective treatments. IBS aetiology is most likely multi-factorial involving biological, psychological and social factors. Visceral hyperalgesia (or hypersensitivity) and visceral hypervigilance, which could be mediated by peripheral, spinal, and/or central pathways, constitute key concepts in current research on pathophysiological mechanisms of visceral hyperalgesia. The role of central nervous system mechanisms along the "brain-gut axis" is increasingly appreciated, owing to accumulating evidence from brain imaging studies that neural processing of visceral stimuli is altered in IBS together with long-standing knowledge regarding the contribution of stress and negative emotions to symptom frequency and severity. At the same time, there is also growing evidence suggesting that peripheral immune mechanisms and disturbed neuro-immune communication could play a role in the pathophysiology of visceral hyperalgesia. This review presents recent advances in research on the pathophysiology of visceral hyperalgesia in IBS, with a focus on the role of stress and anxiety in central and peripheral response to visceral pain stimuli. Together, these findings support that in addition to lower pain thresholds displayed by a significant proportion of patients, the evaluation of pain appears to be altered in IBS. This may be attributable to affective disturbances, negative emotions in anticipation of or during visceral stimulation, and altered pain-related expectations and learning processes. Disturbed "top-down" emotional and cognitive pain modulation in IBS is reflected by functional and possibly structural brain changes involving prefrontal as well as cingulate regions. At the same time, there is growing evidence linking peripheral and mucosal immune changes and abdominal pain in IBS, supporting disturbed peripheral pain signalling. Findings in post-infectious IBS emphasize the interaction between centrally-mediated psychosocial risk factors and local inflammation in predicting long-term IBS symptoms. Investigating afferent immune-to-brain communication in visceral hyperalgesia as a component of the sickness response constitutes a promising future research goal. Copyright © 2010 Elsevier Inc. All rights reserved.

Induction of Migraine-Like Photophobic Behavior in Mice by Both Peripheral and Central CGRP Mechanisms

PubMed Central

Mason, Bianca N.; Kaiser, Eric A.; Kuburas, Adisa; Loomis, Maria-Cristina M.; Latham, John A.; Garcia-Martinez, Leon F.

2017-01-01

The neuropeptide calcitonin gene-related peptide (CGRP) is a key player in migraine. Although migraine can be treated using CGRP antagonists that act peripherally, the relevant sites of CGRP action remain unknown. To address the role of CGRP both within and outside the CNS, we used CGRP-induced light-aversive behavior in mice as a measure of migraine-associated photophobia. Peripheral (intraperitoneal) injection of CGRP resulted in light-aversive behavior in wild-type CD1 mice similar to aversion seen previously after central (intracerebroventricular) injection. The phenotype was also observed in C57BL/6J mice, although to a lesser degree and with more variability. After intraperitoneal CGRP, motility was decreased in the dark only, similar to motility changes after intracerebroventricular CGRP. In addition, as with intracerebroventricular CGRP, there was no general increase in anxiety as measured in an open-field assay after intraperitoneal CGRP. Importantly, two clinically effective migraine drugs, the 5-HT1B/D agonist sumatriptan and a CGRP-blocking monoclonal antibody, attenuated the peripheral CGRP-induced light aversion and motility behaviors. To begin to address the mechanism of peripheral CGRP action, we used transgenic CGRP-sensitized mice that have elevated levels of the CGRP receptor hRAMP1 subunit in nervous tissue (nestin/hRAMP1). Surprisingly, sensitivity to low light was not seen after intraperitoneal CGRP injection, but was seen after intracerebroventricular CGRP injection. These results suggest that CGRP can act in both the periphery and the brain by distinct mechanisms and that CGRP actions may be transmitted to the CNS via indirect sensitization of peripheral nerves. SIGNIFICANCE STATEMENT The neuropeptide calcitonin gene-related peptide (CGRP) is a central player in migraine pathogenesis, yet its site(s) of action remains unknown. Some preclinical studies have pointed to central sites in the brain and brainstem. However, a peripheral site of action is indicated by the ability of intravenous CGRP to trigger migraine in humans and the efficacy of CGRP receptor antagonists that evidently do no penetrate the CNS in effective amounts. Resolving this issue is particularly important given recent clinical trials showing that anti-CGRP monoclonal antibodies can reduce and even prevent migraine attacks. In this study, we report that CGRP can act in both the brain and the periphery of the mouse to cause migraine-like photophobia by apparently distinct mechanisms. PMID:28053042

[Dopamine neurotransmission of peripheral blood lymphocytes is a potential biomarker of psychiatric and neurological disorders].

PubMed

Taraskina, A E; Nasyrova, R F; Grunina, M N; Zabotina, A M; Ivashchenko, D V; Ershov, E E; Sosin, D N; Kirnichnaya, K A; Ivanov, M V; Krupitsky, E M

2015-01-01

Current literature on a role of dopamine in the development of mental and neurological disorders suggests that the discovery of endogenous dopamine in peripheral blood lymphocytes gave rise to a new line of research. Dopamine receptors are not only found on cells of the innate immune response (nonspecific), but also on cells of adaptive immune response (specific): T and B lymphocytes. These facts bring a new evidence of interrelationships between the peripheral immune system, neuroinflammation and neurodegeneration and suggest new ways for investigation of the pathogenesis of different mental and neurological disorders, in particular Parkinson's disease, Alzheimer's disease and schizophrenia. There is strong evidence that ligands of dopamine receptors can change the expression of coding genes both in central neurons and in peripheral cells. Thus, peripheral blood lymphocytes may prove a cellular tool to identify dopamine transmission disturbances in neuropsychiatric diseases, as well as to monitor the effects of pharmacological treatment.

Peripheral metabolic actions of leptin.

PubMed

Muoio, Deborah M; Lynis Dohm, G

2002-12-01

The adipocyte-derived hormone, leptin, regulates food intake and systemic fuel metabolism; ob /ob mice, which lack functional leptin, exhibit an obesity syndrome that is similar to morbid obesity in humans. Leptin receptors are expressed most abundantly in the brain but are also present in several peripheral tissues. The role of leptin in controlling energy homeostasis has thus far focused on brain receptors and neuroendocrine pathways that regulate feeding behaviour and sympathetic nervous system activity. This chapter focuses on mounting evidence that leptin's effects on energy balance are also mediated by direct peripheral actions on key metabolic organs such as skeletal muscle, liver, pancreas and adipose tissue. Strong evidence indicates that peripheral leptin receptors regulate cellular lipid balance, favouring beta-oxidation over triacylglycerol storage. There are data to indicate that peripheral leptin also modulates glucose metabolism and insulin action; however, its precise role in controlling gluco-regulatory pathways remains uncertain and requires further investigation.

Peripheral Nerve Dysfunction in Middle-Aged Subjects Born with Thalidomide Embryopathy

PubMed Central

Nicotra, Alessia; Newman, Claus; Johnson, Martin; Eremin, Oleg; Friede, Tim; Malik, Omar; Nicholas, Richard

2016-01-01

Background Phocomelia is an extremely rare congenital malformation that emerged as one extreme of a range of defects resulting from in utero exposure to thalidomide. Individuals with thalidomide embryopathy (TE) have reported developing symptoms suggestive of peripheral nervous system dysfunction in the mal-developed limbs in later life. Methods Case control study comparing TE subjects with upper limb anomalies and neuropathic symptoms with healthy controls using standard neurophysiological testing. Other causes of a peripheral neuropathy were excluded prior to assessment. Results Clinical examination of 17 subjects with TE (aged 50.4±1.3 [mean±standard deviation] years, 10 females) and 17 controls (37.9±9.0 years; 8 females) demonstrated features of upper limb compressive neuropathy in three-quarters of subjects. Additionally there were examination findings suggestive of mild sensory neuropathy in the lower limbs (n = 1), L5 radiculopathic sensory impairment (n = 1) and cervical myelopathy (n = 1). In TE there were electrophysiological changes consistent with a median large fibre neuropathic abnormality (mean compound muscle action potential difference -6.3 mV ([-9.3, -3.3], p = 0.0002) ([95% CI], p-value)) and reduced sympathetic skin response amplitudes (-0.8 mV ([-1.5, -0.2], p = 0.0089)) in the affected upper limbs. In the lower limbs there was evidence of sural nerve dysfunction (sensory nerve action potential -5.8 μV ([-10.7, -0.8], p = 0.0232)) and impaired warm perception thresholds (+3.0°C ([0.6, 5.4], p = 0.0169)). Conclusions We found a range of clinical features relevant to individuals with TE beyond upper limb compressive neuropathies supporting the need for a detailed neurological examination to exclude other treatable pathologies. The electrophysiological evidence of large and small fibre axonal nerve dysfunction in symptomatic and asymptomatic limbs may be a result of the original insult and merits further investigation. PMID:27100829

Incidence and relative risk of peripheral neuropathy in cancer patients treated with eribulin: a meta-analysis.

PubMed

Peng, Ling; Hong, Yun; Ye, Xianghua; Shi, Peng; Zhang, Junyan; Wang, Yina; Zhao, Qiong

2017-12-19

Eribulin is a microtubule inhibitor, which is approved for the treatment of breast cancer. Peripheral neuropathy has been reported in the studies of eribulin, but the incidence and relative risk (RR) of eribulin-associated peripheral neuropathy varied greatly in cancer patients. The purpose of this meta-analysis was to determine the overall incidence and RR of eribulin-associated peripheral neuropathy in cancer patients. Pubmed database and Embase and abstracts presented at the American Society of Clinical Oncology (ASCO) meetings were systematically reviewed for primary studies. Eligible studies included prospective clinical trials and expanded access programs of cancer patients treated with eribulin. Statistical analyses were performed to calculate the incidences, RRs, and 95% confidence intervals (CIs). Altogether, 4,849 patients from 19 clinical trials were selected for this meta-analysis. The incidences of all-grade and high-grade peripheral neuropathy were 27.5% (95% CI: 23.3-32.4%) and 4.7% (95% CI: 3.6-6.2%), respectively. The relative risks of peripheral neuropathy of eribulin compared to control were increased for all-grade (RR = 1.89, 95% CI: 1.10-3.25) but not statistically significant for high-grade (RR = 2.98, 95% CI: 0.71-12.42). The use of eribulin is associated with an increased incidence of peripheral neuropathy. The RR is increased for all-grade peripheral neuropathy.

Supera self-expanding stents for endovascular treatment of femoropopliteal disease: a review of the clinical evidence

PubMed Central

Bishu, Kalkidan; Armstrong, Ehrin J

2015-01-01

Femoropopliteal lesions account for a significant proportion of endovascular interventions for peripheral artery disease in patients with disabling claudication or chronic limb ischemia. The femoropopliteal artery crosses two joint structures (hip and knee joints) and courses through the muscular adductor canal in the thigh, which places the artery at increased biomechanical stress. There is a critical need for stent platforms with a reduced risk of stent fracture while maintaining patency during long-term follow-up. The Supera peripheral stent system has a braided nickel–titanium alloy stent designed to withstand the unique stressors along the course of the femoropopliteal artery. This design may be associated with improved patency in association with reduced stent fracture rates on short- and medium-term follow-up. Further studies, including randomized controlled studies, comparing the Supera interwoven nickel–titanium alloy stent system with other stent platforms and angioplasty alone are needed. PMID:26203255

[Stem cell mobilization after coronary artery bypass grafting].

PubMed

Gaspardone, Achille; De Fabritiis, Paolo; Scaffa, Raffaele; Nardi, Paolo; Palombi, Francesca; Versaci, Francesco; Chiariello, Luigi

2004-01-01

Recently, the role of stem cells as a potential therapeutic tool for ischemic heart disease has been evaluated by a number of experimental and clinical studies. Although preliminary clinical data appear to be promising, the precise pathophysiological role of stem cell mobilization during acute myocardial ischemia remains uncertain. The present study was aimed at assessing factors affecting stem cell mobilization after coronary artery bypass grafting used as a clinical model of controlled myocardial ischemia. Eighteen patients (16 men, 2 women, mean age 66 +/- 8 years) with three-vessel coronary artery disease undergoing coronary artery bypass grafting were included in the study; 24 age- and sex-matched healthy subjects served as controls. On admission, 10 patients had stable angina and 8 had unstable angina. Clinical history and instrumental evidence of previous myocardial infarction were present in 11 patients. Venous peripheral blood was sampled at baseline and 6, 24, 48 and 72 hours after coronary surgery. Duration of cardiac arrest and extracorporeal circulation were recorded as well as the release of total creatine kinase (CK), CK-MB, troponin I and C-reactive protein. CD34+ stem cells were analyzed by flow cytometry according to published methods. In patients with ischemic heart disease the peripheral concentration of CD34+ cells was higher than that of control subjects (0.202 +/- 0.30 vs 0.068 +/- 0.059%, p = 0.03). However, patients with stable and unstable angina had similar concentration of CD34+ cells (0.171 +/- 0.33 vs 0.241 +/- 0.275%, p = 0.63) as well as patients with and without previous myocardial infarction (0.134 +/- 0.19 vs 0.245 +/- 0.352%, p = 0.4). Coronary artery bypass grafting caused a non-significant increase in concentration of CD34+ cells at 24 hours which was similar in patients with stable and unstable angina. Finally, no significant correlation was found between peripheral concentration of CD34+ cells and aortic clamping and extracorporeal circulation duration, peak release of total CK, CK-MB, troponin I and C-reactive protein. Peripheral concentration of CD34+ stem cells is higher in patients with ischemic heart disease than in healthy controls but it is similar in patients with stable and unstable coronary syndromes. Peripheral mobilization of CD34+ cells is not correlated with the duration and severity of ischemic insult induced by surgical cardiac arrest. These preliminary findings suggest that CD34+ cell mobilization may be modulated more by tonically active than phasic factors.

Peripheral neuropathy in HIV: an analysis of evidence-based approaches.

PubMed

Nicholas, Patrice K; Corless, Inge B; Evans, Linda A

2014-01-01

Peripheral neuropathy is a common and vexing symptom for people living with HIV infection (PLWH). Neuropathy occurs in several different syndromes and is identified in the literature as distal sensory polyneuropathy or distal sensory peripheral neuropathy. More recently, the HIV literature has focused on the syndrome as painful HIV-associated sensory neuropathy, addressing the symptom rather than the underlying pathophysiology. Assessment of neuropathy in PLWH is critical and must be incorporated into nursing practice for each visit. Neuropathy has been attributed to the direct effects of HIV, exposure to antiretroviral medications (particularly the nucleoside reverse transcriptase inhibitors), advanced immune suppression, and comorbid tuberculosis infection and exposure to antituberculosis medications. Evidence supports the importance of addressing neuropathy in PLWH with pharmacologic treatment regimens and complementary/alternative approaches. This paper examines the pathophysiology, evidence, and approaches to managing peripheral neuropathy. A case study has been included to illustrate a patient's experience with neuropathy symptoms. Copyright © 2014 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Dietary anaplerotic therapy improves peripheral tissue energy metabolism in patients with Huntington's disease

PubMed Central

Mochel, Fanny; Duteil, Sandrine; Marelli, Cécilia; Jauffret, Céline; Barles, Agnès; Holm, Janette; Sweetman, Lawrence; Benoist, Jean-François; Rabier, Daniel; Carlier, Pierre G; Durr, Alexandra

2010-01-01

We previously identified a systemic metabolic defect associated with early weight loss in patients with Huntington's disease (HD), suggesting a lack of substrates for the Krebs cycle. Dietary anaplerotic therapy with triheptanoin is used in clinical trials to promote energy production in patients with peripheral and brain Krebs cycle deficit, as its metabolites – C5 ketone bodies – cross the blood–brain barrier. We conducted a short-term clinical trial in six HD patients (UHDRS (Unified Huntington Disease Rating Scale)=33±13, 15–49) to monitor the tolerability of triheptanoin. We also assessed peripheral markers of short-term efficacy that were shown to be altered in the early stages of HD, that is, low serum IGF1 and 31P-NMR spectroscopy (NMRS) in muscle. At baseline, 31P-NMRS displayed two patients with end-exercise muscle acidosis despite a low work output. On day 2, the introduction of triheptanoin was well tolerated in all patients, and in particular, there was no evidence of mitochondrial overload from triheptanoin-derived metabolites. After 4 days of triheptanoin-enriched diet, muscle pH regulation was normalized in the two patients with pretreatment metabolic abnormalities. A significant increase in serum IGF1 was also observed in all patients (205±60 ng/ml versus 246±68 ng/ml, P=0.010). This study provides a rationale for extending our anaplerotic approach with triheptanoin in HD. PMID:20512158

CX3CL1-mediated macrophage activation contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy.

PubMed

Huang, Zhen-Zhen; Li, Dai; Liu, Cui-Cui; Cui, Yu; Zhu, He-Quan; Zhang, Wen-Wen; Li, Yong-Yong; Xin, Wen-Jun

2014-08-01

Painful peripheral neuropathy is a dose-limiting side effect of paclitaxel therapy, which hampers the optimal clinical management of chemotherapy in cancer patients. Currently the underlying mechanisms remain largely unknown. Here we showed that the clinically relevant dose of paclitaxel (3×8mg/kg, cumulative dose 24mg/kg) induced significant upregulation of the chemokine CX3CL1 in the A-fiber primary sensory neurons in vivo and in vitro and infiltration of macrophages into the dorsal root ganglion (DRG) in rats. Paclitaxel treatment also increased cleaved caspase-3 expression, induced the loss of primary afferent terminal fibers and decreased sciatic-evoked A-fiber responses in the spinal dorsal horn, indicating DRG neuronal apoptosis induced by paclitaxel. In addition, the paclitaxel-induced DRG neuronal apoptosis occurred exclusively in the presence of macrophage in vitro study. Intrathecal or systemic injection of CX3CL1 neutralizing antibody blocked paclitaxel-induced macrophage recruitment and neuronal apoptosis in the DRG, and also attenuated paclitaxel-induced allodynia. Furthermore, depletion of macrophage by systemic administration of clodronate inhibited paclitaxel-induced allodynia. Blocking CX3CL1 decreased activation of p38 MAPK in the macrophage, and inhibition of p38 MAPK activity blocked the neuronal apoptosis and development of mechanical allodynia induced by paclitaxel. These findings provide novel evidence that CX3CL1-recruited macrophage contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral neuropathy. Copyright © 2014 Elsevier Inc. All rights reserved.

Granulocyte-mobilized bone marrow.

PubMed

Arcese, William; De Angelis, Gottardo; Cerretti, Raffaella

2012-11-01

In the last few years, mobilized peripheral blood has overcome bone marrow as a graft source, but, despite the evidence of a more rapid engraftment, the incidence of chronic graft-versus-host disease is significantly higher with, consequently, more transplant-related mortality on the long follow-up. Overall, the posttransplant outcome of mobilized peripheral blood recipients is similar to that of patients who are bone marrow grafted. More recently, the use of bone marrow after granulocyte colony-stimulating factor (G-CSF) donor priming has been introduced in the transplant practice. Herein, we review biological acquisitions and clinical results on the use of G-CSF-primed bone marrow as a source of hematopoietic stem cells (HSC) for allogeneic stem cell transplantation. G-CSF the increases the HSC compartment and exerts an intense immunoregulatory effect on marrow T-cells resulting in the shift from Th1 to Th2 phenotype with higher production of anti-inflammatory cytokines. The potential advantages of these biological effects have been translated in the clinical practice by using G-CSF primed unmanipulated bone marrow in the setting of transplant from human leukocyte antigen (HLA)-haploidentical donor with highly encouraging results. For patients lacking an HLA-identical sibling, the transplant of G-CSF primed unmanipulated bone marrow from a haploidentical donor combined with an intense in-vivo immunosuppression is a valid alternative achieving results that are well comparable with those reported for umbilical cord blood, HLA-matched unrelated peripheral blood/bone marrow or T-cell-depleted haploidentical transplant.

High resolution ultrasonography of the tibial nerve in diabetic peripheral neuropathy.

PubMed

Singh, Kunwarpal; Gupta, Kamlesh; Kaur, Sukhdeep

2017-12-01

High-resolution ultrasonography of the tibial nerve is a fast and non invasive tool for diagnosis of diabetic peripheral neuropathy. Our study was aimed at finding out the correlation of the cross sectional area and maximum thickness of nerve fascicles of the tibial nerve with the presence and severity of diabetic peripheral neuropathy. 75 patients with type 2 diabetes mellitus clinically diagnosed with diabetic peripheral neuropathy were analysed, and the severity of neuropathy was determined using the Toronto Clinical Neuropathy Score. 58 diabetic patients with no clinical suspicion of diabetic peripheral neuropathy and 75 healthy non-diabetic subjects were taken as controls. The cross sectional area and maximum thickness of nerve fascicles of the tibial nerves were calculated 3 cm cranial to the medial malleolus in both lower limbs. The mean cross sectional area (22.63 +/- 2.66 mm 2 ) and maximum thickness of nerve fascicles (0.70 mm) of the tibial nerves in patients with diabetic peripheral neuropathy compared with both control groups was significantly larger, and statistically significant correlation was found with the Toronto Clinical Neuropathy Score ( p < 0.001). The diabetic patients with no signs of peripheral neuropathy had a larger mean cross sectional area (14.40 +/- 1.72 mm 2 ) and maximum thickness of nerve fascicles of the tibial nerve (0.40 mm) than healthy non-diabetic subjects (12.42 +/- 1.01 mm 2 and 0.30 mm respectively). The cross sectional area and maximum thickness of nerve fascicles of the tibial nerve is larger in diabetic patients with or without peripheral neuropathy than in healthy control subjects, and ultrasonography can be used as a good screening tool in these patients.

Circulating endothelial and progenitor cells: Evidence from acute and long-term exercise effects

PubMed Central

Koutroumpi, Matina; Dimopoulos, Stavros; Psarra, Katherini; Kyprianou, Theodoros; Nanas, Serafim

2012-01-01

Circulating bone-marrow-derived cells, named endothelial progenitor cells (EPCs), are capable of maintaining, generating, and replacing terminally differentiated cells within their own specific tissue as a consequence of physiological cell turnover or tissue damage due to injury. Endothelium maintenance and restoration of normal endothelial cell function is guaranteed by a complex physiological procedure in which EPCs play a significant role. Decreased number of peripheral blood EPCs has been associated with endothelial dysfunction and high cardiovascular risk. In this review, we initially report current knowledge with regard to the role of EPCs in healthy subjects and the clinical value of EPCs in different disease populations such as arterial hypertension, obstructive sleep-apnea syndrome, obesity, diabetes mellitus, peripheral arterial disease, coronary artery disease, pulmonary hypertension, and heart failure. Recent studies have introduced the novel concept that physical activity, either performed as a single exercise session or performed as part of an exercise training program, results in a significant increase of circulating EPCs. In the second part of this review we provide preliminary evidence from recent studies investigating the effects of acute and long-term exercise in healthy subjects and athletes as well as in disease populations. PMID:23272272

Otoneurological symptoms in Brazilian fishermen exposed over a long period to carbon monoxide and noise.

PubMed

Zeigelboim, Bianca Simone; Santos da Carvalho, Hugo Amilton; Gonçalves, Claudia Giglio de Oliveira; Albizu, Evelyn Joice; Marques, Jair Mendes; Fuck, Bruna Carla; Cardoso, Rafaella

2015-01-01

Fishing, one of the oldest productive activities, is an important sector of the Brazilian economy as well as the world economy. To evaluate the vestibular behavior in population of fishermen. It was realized as a retrospective and cross-sectional study. Thirty fishermen [mean age 49.5 (± 8.5) years] whose age ranged from 33 years to 67 years were submitted to anamnesis, otorhinolaryngological evaluation, and vestibular examination through the electronystagmography (ENG). The most evident otoneurological symptoms were: Tinnitus (66.7%), dizziness (63.3%), and hearing loss (53.3%). The most evident clinical symptoms were: Fatigue (36.7%), anxiety (23.3%), and depression (16.7%). There were alterations in the vestibular examination of 13 (43.3%) fishermen in the caloric test. There was a prevalence of alteration in the peripheral vestibular system and there was a major frequency of the peripheral vestibular irritative syndrome (30.0%). The otoneurological complaints were frequent in the population studied that verifies the importance of allowing labyrinth examinations and the need for adopting preventive measures related to noise exposure to carbon monoxide (CO), since they can cause and/enhance various manifestations of labyrinthine vestibular impairment that can affect the quality of life of these workers.

Central nervous system regulation of hepatic lipid and lipoprotein metabolism.

PubMed

Taher, Jennifer; Farr, Sarah; Adeli, Khosrow

2017-02-01

Hepatic lipid and lipoprotein metabolism is an important determinant of fasting dyslipidemia and the development of fatty liver disease. Although endocrine factors like insulin have known effects on hepatic lipid homeostasis, emerging evidence also supports a regulatory role for the central nervous system (CNS) and neuronal networks. This review summarizes evidence implicating a bidirectional liver-brain axis in maintaining metabolic lipid homeostasis, and discusses clinical implications in insulin-resistant states. The liver utilizes sympathetic and parasympathetic afferent and efferent fibers to communicate with key regulatory centers in the brain including the hypothalamus. Hypothalamic anorexigenic and orexigenic peptides signal to the liver via neuronal networks to modulate lipid content and VLDL production. In addition, peripheral hormones such as insulin, leptin, and glucagon-like-peptide-1 exert control over hepatic lipid by acting directly within the CNS or via peripheral nerves. Central regulation of lipid metabolism in other organs including white and brown adipose tissue may also contribute to hepatic lipid content indirectly via free fatty acid release and changes in lipoprotein clearance. The CNS communicates with the liver in a bidirectional manner to regulate hepatic lipid metabolism and lipoprotein production. Impairments in these pathways may contribute to dyslipidemia and hepatic steatosis in insulin-resistant states.

Hematologic changes after total body irradiation and autologous transplantation of hematopoietic peripheral blood progenitor cells in dogs with lymphoma.

PubMed

Escobar, C; Grindem, C; Neel, J A; Suter, S E

2012-03-01

Dogs with and without lymphoma have undergone hematopoietic cell transplantation in a research setting for decades. North Carolina State University is currently treating dogs with B- and T-cell lymphoma in a clinical setting with autologous peripheral blood progenitor cell transplants, using peripheral blood CD34+ progenitor cells harvested using an apheresis machine. Complete blood counts were performed daily for 15 to 19 days posttransplantation to monitor peripheral blood cell nadirs and subsequent CD34+ cell engraftment. This study documents the hematologic toxicities of total body irradiation in 10 dogs and the subsequent recovery of the affected cell lines after peripheral blood progenitor cell transplant, indicating successful CD34+ engraftment. All peripheral blood cell lines, excluding red blood cells, experienced grade 4 toxicities. All dogs had ≥ 500 neutrophils/μl by day 12, while thrombocytopenia persisted for many weeks. All dogs were clinically normal at discharge.

Peripheral neuropathy associated with mitochondrial disease in children.

PubMed

Menezes, Manoj P; Ouvrier, Robert A

2012-05-01

Mitochondrial diseases in children are often associated with a peripheral neuropathy but the presence of the neuropathy is under-recognized because of the overwhelming involvement of the central nervous system (CNS). These mitochondrial neuropathies are heterogeneous in their clinical, neurophysiological, and histopathological characteristics. In this article, we provide a comprehensive review of childhood mitochondrial neuropathy. Early recognition of neuropathy may help with the identification of the mitochondrial syndrome. While it is not definite that the characteristics of the neuropathy would help in directing genetic testing without the requirement for invasive skin, muscle or liver biopsies, there appears to be some evidence for this hypothesis in Leigh syndrome, in which nuclear SURF1 mutations cause a demyelinating neuropathy and mitochondrial DNA MTATP6 mutations cause an axonal neuropathy. POLG1 mutations, especially when associated with late-onset phenotypes, appear to cause a predominantly sensory neuropathy with prominent ataxia. The identification of the peripheral neuropathy also helps to target genetic testing in the mitochondrial optic neuropathies. Although often subclinical, the peripheral neuropathy may occasionally be symptomatic and cause significant disability. Where it is symptomatic, recognition of the neuropathy will help the early institution of rehabilitative therapy. We therefore suggest that nerve conduction studies should be a part of the early evaluation of children with suspected mitochondrial disease. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

Humoral and Cellular Immunity Changed after Traumatic Brain Injury in Human Patients.

PubMed

Wang, Jia-Wei; Li, Jin-Ping; Song, Ying-Lun; Zhao, Qi-Huang

2017-01-01

Previous studies have suggested that there is a disproportionally higher risk of infection following traumatic brain injury (TBI). This predisposition to infection may be driven by a poorly understood, brain-specific response in the immune system after TBI. However, there is a lack of studies that have fully characterized TBI patients to understand the relationship between TBI and peripheral immune function. In the present study, markers for humoral immunity and cellular immunity were measured for up to 2 weeks in the peripheral blood of 37 patients with TBI in order to elucidate the time course and the type of the peripheral immune response following TBI. 12 relatively healthy individuals without TBI and other neurological diseases were enrolled into the control group. Our data indicated that TBI could induce significant changes in humoral immunity characterized by a decrease in IgG and IgM levels and an increase in the complements C3 and C4 levels in comparison with the control group. Moreover, compared with the control group, a significant reduction in peripheral blood CD3 + and CD3 + CD4 + lymphocyte counts occurred early (days 1-3) following the onset of trauma. These results provide evidence that TBI is associated with substantial changes in humoral immunity and cellular immunity, which may explain the high incidence of infection encountered in these patients. © 2017 by the Association of Clinical Scientists, Inc.

Do Peripheral Refraction and Aberration Profiles Vary with the Type of Myopia? - An Illustration Using a Ray-Tracing Approach

PubMed Central

Bakaraju, Ravi C.; Ehrmann, Klaus; Papas, Eric B.; Ho, Arthur

2010-01-01

Purpose Myopia is considered to be the most common refractive error occurring in children and young adults, around the world. Motivated to elucidate how the process of emmetropization is disrupted, potentially causing myopia and its progression, researchers have shown great interest in peripheral refraction. This study assessed the effect of the myopia type, either refractive or axial, on peripheral refraction and aberration profiles. Methods Using customized schematic eye models for myopia in a ray tracing algorithm, peripheral aberrations, including the refractive error, were calculated as a function of myopia type. Results In all the selected models, hyperopic shifts in the mean spherical equivalent (MSE) component were found whose magnitude seemed to be largely dependent on the field angle. The MSE profiles showed larger hyperopic shifts for the axial type of myopic models than the refractive ones and were evident in -4 and -6 D prescriptions. Additionally, greater levels of astigmatic component (J180) were also seen in axial-length-dependent models, while refractive models showed higher levels of spherical aberration and coma. Conclusion This study has indicated that myopic eyes with primarily an axial component may have a greater risk of progression than their refractive counterparts albeit with the same degree of refractive error. This prediction emerges from the presented theoretical ray tracing model and, therefore, requires clinical confirmation.

Insulin-like growth factor-1: a possible marker for emotional and cognitive disturbances, and treatment effectiveness in major depressive disorder.

PubMed

Levada, Oleg A; Troyan, Alexandra S

2017-01-01

Depression and cognitive dysfunction share a common neuropathological platform. Abnormal neural plasticity in the frontolimbic circuits has been linked to changes in the expression of neurotrophic factors, including IGF-1. These changes may result in clinical abnormalities observed over the course of major depressive disorder (MDD), including cognitive dysfunction. The present review aimed to summarize evidence regarding abnormalities of peripheral IGF-1 in MDD patients and assess a marker and predictive role of the neurotrophin for emotional and cognitive disturbances, and treatment effectiveness. A literature search of the PubMed database was conducted for studies, in which peripheral IGF-1 levels were evaluated. Our analysis revealed four main findings: (1) IGF-1 levels in MDD patients mismatch across the studies, which may arise from various factors, e.g., age, gender, the course of the disease, presence of cognitive impairment, ongoing therapy, or general health conditions; (2) the initial peripheral IGF-1 levels may predict the occurrence of depression in future; (3) peripheral IGF-1 levels may reflect cognitive dysfunction, although the data is limited; (4) it is difficult to evaluate the influence of treatment on IGF-1 levels as there is discrepancy of this growth factor among the studies at baseline, although most of them showed a decrease in IGF-1 levels after treatment.

Clinical Characteristics and Treatment Response of Peripheral Neuropathy in the Presence of Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome): Experience at a Single Tertiary Center.

PubMed

Cho, Hye Jin; Yune, Sehyo; Seok, Jin Myoung; Cho, Eun Bin; Min, Ju Hong; Seo, Yeon Lim; Lee, Byung Jae; Kim, Byoung Joon; Choi, Dong Chull

2017-01-01

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic small-vessel vasculitis accompanied by asthma, eosinophilia, and eosinophilic inflammation of various tissues including the peripheral nerves. This study investigated the clinical course and long-term outcomes of peripheral neuropathy in patients with EGPA. Seventy-one patients with physician-diagnosed EGPA were identified at Samsung Medical Center between January 1995 and April 2014. Sixty-one of these patients were followed-up for more than 1 year and received corticosteroid therapy with or without intravenous cyclophosphamide pulse therapy for 6 to 18 months. Medical records of the 61 patients including demographic data, clinical features, laboratory and pathological findings, treatments, and outcomes were reviewed. Peripheral neuropathy as a manifestation of EGPA was present in 46 (75%) of the 61 patients. The mean follow-up duration of the patients with neuropathy was 6.4 years (range 1.2-18.8 years). The scores on the neurological functional disability scale before and after the combination treatment with corticosteroid and cyclophosphamide were 2.43±0.86 and 0.54±0.95 (mean±SD; p<0.001), respectively. The peripheral neuropathy relapsed in one patient. The long-term clinical outcome of peripheral neuropathy in patients with EGPA receiving initial corticosteroid and cyclophosphamide combination therapy was favorable with a very low relapse rate.

A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure.

PubMed

Jasti, Dushyanth Babu; Mallipeddi, Sarat; Apparao, A; Vengamma, B; Sivakumar, V; Kolli, Satyarao

2017-01-01

To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure ( n = 100) and severe renal failure patients ( n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics.

Development of a clinical prediction rule to improve peripheral intravenous cannulae first attempt success in the emergency department and reduce post insertion failure rates: the Vascular Access Decisions in the Emergency Room (VADER) study protocol

PubMed Central

Carr, Peter J; Rippey, James C R; Cooke, Marie L; Bharat, Chrianna; Murray, Kevin; Higgins, Niall S; Foale, Aileen; Rickard, Claire M

2016-01-01

Introduction Peripheral intravenous cannula (PIVC) insertion is one of the most common clinical interventions performed in emergency care worldwide. However, factors associated with successful PIVC placement and maintenance are not well understood. This study seeks to determine the predictors of first time PIVC insertion success in emergency department (ED) and identify the rationale for removal of the ED inserted PIVC in patients admitted to the hospital ward. Reducing failed insertion attempts and improving peripheral intravenous cannulation practice could lead to better staff and patient experiences, as well as improving hospital efficiency. Methods and analysis We propose an observational cohort study of PIVC insertions in a patient population presenting to ED, with follow-up observation of the PIVC in subsequent admissions to the hospital ward. We will collect specific PIVC observational data such as; clinician factors, patient factors, device information and clinical practice variables. Trained researchers will gather ED PIVC insertion data to identify predictors of insertion success. In those admitted from the ED, we will determine the dwell time of the ED-inserted PIVC. Multivariate regression analyses will be used to identify factors associated with insertions success and PIVC failure and standard statistical validation techniques will be used to create and assess the effectiveness of a clinical predication rule. Ethics and dissemination The findings of our study will provide new evidence to improve insertion success rates in the ED setting and identify strategies to reduce premature device failure for patients admitted to hospital wards. Results will unravel a complexity of factors that contribute to unsuccessful PIVC attempts such as patient and clinician factors along with the products, technologies and infusates used. Trial registration number ACTRN12615000588594; Pre-results. PMID:26868942

Development of a clinical prediction rule to improve peripheral intravenous cannulae first attempt success in the emergency department and reduce post insertion failure rates: the Vascular Access Decisions in the Emergency Room (VADER) study protocol.

PubMed

Carr, Peter J; Rippey, James C R; Cooke, Marie L; Bharat, Chrianna; Murray, Kevin; Higgins, Niall S; Foale, Aileen; Rickard, Claire M

2016-02-11

Peripheral intravenous cannula (PIVC) insertion is one of the most common clinical interventions performed in emergency care worldwide. However, factors associated with successful PIVC placement and maintenance are not well understood. This study seeks to determine the predictors of first time PIVC insertion success in emergency department (ED) and identify the rationale for removal of the ED inserted PIVC in patients admitted to the hospital ward. Reducing failed insertion attempts and improving peripheral intravenous cannulation practice could lead to better staff and patient experiences, as well as improving hospital efficiency. We propose an observational cohort study of PIVC insertions in a patient population presenting to ED, with follow-up observation of the PIVC in subsequent admissions to the hospital ward. We will collect specific PIVC observational data such as; clinician factors, patient factors, device information and clinical practice variables. Trained researchers will gather ED PIVC insertion data to identify predictors of insertion success. In those admitted from the ED, we will determine the dwell time of the ED-inserted PIVC. Multivariate regression analyses will be used to identify factors associated with insertions success and PIVC failure and standard statistical validation techniques will be used to create and assess the effectiveness of a clinical predication rule. The findings of our study will provide new evidence to improve insertion success rates in the ED setting and identify strategies to reduce premature device failure for patients admitted to hospital wards. Results will unravel a complexity of factors that contribute to unsuccessful PIVC attempts such as patient and clinician factors along with the products, technologies and infusates used. ACTRN12615000588594; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Challenges Evaluating Chemotherapy-Induced Peripheral Neuropathy in Childhood Cancer Survivors.

PubMed

Mohrmann, Caroline; Armer, Jane; Hayashi, Robert J

Children treated for cancer are exposed to a variety of chemotherapeutic agents with known toxicity to the peripheral nervous system. The side effect of peripheral neuropathy can cause changes in sensation, function, and even cause pain. Although peripheral neuropathy is recognized by pediatric oncology nurses as an important and significant side effect, measuring neuropathy can be quite complex for clinical care and research efforts. With more children surviving a cancer diagnosis today, this issue is increasingly important for childhood cancer survivors. This article has reviewed existing literature examining peripheral neuropathy in childhood cancer survivors with particular interest paid to measurement tools available and needs for future research. It is important for nurses to choose appropriate measures for clinical care and research methods in order to have an impact on patients experiencing this condition.

Electrophysiological measurements of diabetic peripheral neuropathy: A systematic review.

PubMed

Shabeeb, Dheyauldeen; Najafi, Masoud; Hasanzadeh, Gholamreza; Hadian, Mohammed Reza; Musa, Ahmed Eleojio; Shirazi, Alireza

2018-03-28

Peripheral neuropathy is one of the main complications of diabetes mellitus. One of the features of diabetic nerve damage is abnormality of sensory and motor nerve conduction study. An electrophysiological examination can be reproduced and is also a non-invasive approach in the assessment of peripheral nerve function. Population-based and clinical studies have been conducted to validate the sensitivity of these methods. When the diagnosis was based on clinical electrophysiological examination, abnormalities were observed in all patients. In this research, using a review design, we reviewed the issue of clinical electrophysiological examination of diabetic peripheral neuropathy in articles from 2008 to 2017. For this purpose, PubMed, Scopus and Embase databases of journals were used for searching articles. The researchers indicated that diabetes (both types) is a very disturbing health issue in the modern world and should be given serious attention. Based on conducted studies, it was demonstrated that there are different procedures for prevention and treatment of diabetes-related health problems such as diabetic polyneuropathy (DPN). The first objective quantitative indication of the peripheral neuropathy is abnormality of sensory and motor nerve conduction tests. Electrophysiology is accurate, reliable and sensitive. It can be reproduced and also is a noninvasive approach in the assessment of peripheral nerve function. The methodological review has found that the best method for quantitative indication of the peripheral neuropathy compared with all other methods is clinical electrophysiological examination. For best results, standard protocols such as temperature control and equipment calibration are recommended. Copyright © 2018. Published by Elsevier Ltd.

Incidence and relative risk of peripheral neuropathy in cancer patients treated with eribulin: a meta-analysis

PubMed Central

Peng, Ling; Hong, Yun; Ye, Xianghua; Shi, Peng; Zhang, Junyan; Wang, Yina; Zhao, Qiong

2017-01-01

Background Eribulin is a microtubule inhibitor, which is approved for the treatment of breast cancer. Peripheral neuropathy has been reported in the studies of eribulin, but the incidence and relative risk (RR) of eribulin-associated peripheral neuropathy varied greatly in cancer patients. The purpose of this meta-analysis was to determine the overall incidence and RR of eribulin-associated peripheral neuropathy in cancer patients. Materials and Methods Pubmed database and Embase and abstracts presented at the American Society of Clinical Oncology (ASCO) meetings were systematically reviewed for primary studies. Eligible studies included prospective clinical trials and expanded access programs of cancer patients treated with eribulin. Statistical analyses were performed to calculate the incidences, RRs, and 95% confidence intervals (CIs). Results Altogether, 4,849 patients from 19 clinical trials were selected for this meta-analysis. The incidences of all-grade and high-grade peripheral neuropathy were 27.5% (95% CI: 23.3–32.4%) and 4.7% (95% CI: 3.6–6.2%), respectively. The relative risks of peripheral neuropathy of eribulin compared to control were increased for all-grade (RR = 1.89, 95% CI: 1.10–3.25) but not statistically significant for high-grade (RR = 2.98, 95% CI: 0.71–12.42). Conclusions The use of eribulin is associated with an increased incidence of peripheral neuropathy. The RR is increased for all-grade peripheral neuropathy. PMID:29340112

Subacute peripheral and optic neuropathy syndrome with no evidence of a toxic or nutritional cause.

PubMed

Allen, D; Riordan-Eva, P; Paterson, R W; Hadden, R D M

2013-08-01

The syndrome of subacute simultaneous peripheral neuropathy and bilateral optic neuropathy is known to occur in tropical countries, probably due to malnutrition or toxicity, but not often seen in developed countries. We report seven patients in London who were not malnourished or alcoholic, and in whom no clear cause was found. We retrospectively reviewed the case notes and arranged some further investigations. All patients developed peripheral and bilateral optic neuropathy within 6 months. Patients were aged 30-52, and all of Jamaican birth and race but lived in the UK. Most had subacute, painful ataxic sensory axonal neuropathy or neuronopathy, some with myelopathy. Nerve conduction studies revealed minor demyelinating features in two cases. The optic neuropathy was symmetrical, subacute and monophasic, usually with marked reduction in visual acuity. CSF protein concentration was usually elevated but other laboratory investigations were normal. Patients showed only modest improvement at follow-up. These patients share a common clinical and electrophysiological phenotype, age, ethnicity and elevated CSF protein, but otherwise normal laboratory investigations. The syndrome is a cause of significant morbidity in young people. The cause remains uncertain despite thorough investigation. Copyright © 2013 Elsevier B.V. All rights reserved.

Reduction of Circulating Neutrophils Precedes and Accompanies Type 1 Diabetes

PubMed Central

Valle, Andrea; Giamporcaro, Gian Maria; Scavini, Marina; Stabilini, Angela; Grogan, Pauline; Bianconi, Eleonora; Sebastiani, Guido; Masini, Matilde; Maugeri, Norma; Porretti, Laura; Bonfanti, Riccardo; Meschi, Franco; De Pellegrin, Maurizio; Lesma, Arianna; Rossini, Silvano; Piemonti, Lorenzo; Marchetti, Piero; Dotta, Francesco; Bosi, Emanuele; Battaglia, Manuela

2013-01-01

Human type 1 diabetes (T1D) is an autoimmune disease associated with major histocompatibility complex polymorphisms, β-cell autoantibodies, and autoreactive T cells. However, there is increasing evidence that innate cells may also play critical roles in T1D. We aimed to monitor peripheral immune cells in early stages of T1D (i.e., in healthy autoantibody-positive subjects) and in more advanced phases of the disease (i.e., at disease onset and years after diagnosis). We found a mild but significant and reproducible peripheral neutropenia that both precedes and accompanies the onset of T1D. This reduction was not due to peripheral neutrophil cell death, impaired differentiation, or the presence of anti-neutrophil antibodies. Neutrophils were observed by electron microscopy and immunohistochemical analysis in the exocrine pancreas of multiorgan donors with T1D (both at onset and at later stages of the disease) and not in that of multiorgan donors with type 2 diabetes or nondiabetic donors. These pancreas-infiltrating neutrophils mainly localized at the level of very small blood vessels. Our findings suggest the existence of a hitherto unrecognized clinical phenotype that might reflect unexplored pathogenic pathways underlying T1D. PMID:23349491

Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis.

PubMed

Agah, Elmira; Zardoui, Arshia; Saghazadeh, Amene; Ahmadi, Mona; Tafakhori, Abbas; Rezaei, Nima

2018-01-01

Identifying a reliable biomarker may accelerate diagnosis of multiple sclerosis (MS) and lead to early management of the disease. Accumulating evidence suggest that cerebrospinal fluid (CSF) and peripheral blood concentration of osteopontin (OPN) may have diagnostic and prognostic value in MS. We conducted a systematic review and meta-analysis of studies that measured peripheral blood and CSF levels of OPN in MS patients and controls to evaluate the diagnostic potential of this biomarker better. We searched PubMed, Web of Science and Scopus databases to find articles that measured OPN concentration in peripheral blood and CSF samples from MS patients up to October 19, 2016. Q statistic tests and the I2 index were applied for heterogeneity assessment. If the I2 index was less than 40%, the fixed-effects model was used for meta-analysis. Random-effects meta-analysis was chosen if the I2 value was greater than 40%. After removal of duplicates, 918 articles were identified, and 27 of them fulfilled the inclusion criteria. We included 22 eligible studies in the final meta-analysis. MS patients, in general, had considerably higher levels of OPN in their CSF and blood when compared to all types of controls (p<0.05). When the comparisons were made between different subtypes of MS patients and controls, the results pointed to significantly higher levels of OPN in CSF of MS subgroups (p<0.05). All subtypes of MS patients, except CIS patients, had increased blood levels of OPN compared to controls (p<0.05). In the second set of meta-analyses, we compared the peripheral blood and CSF concentrations of OPN between MS patient subtypes. CIS patients had significantly lower levels of OPN both in their peripheral blood and CSF compared to patients with progressive subtypes of MS (p<0.05). CSF concentration of OPN was significantly higher among RRMS patients compared to the CIS patients and SPMS patients (P<0.05). Finally, patients with active MS had significantly higher OPN levels in their CSF compared to patients with stable disease (P = 0.007). The result of this study confirms that increased levels of OPN exist in CSF and peripheral blood of MS patients and strengthens the evidence regarding the clinical utility of OPN as a promising and validated biomarker for MS.

Biphalin preferentially recruits peripheral opioid receptors to facilitate analgesia in a mouse model of cancer pain - A comparison with morphine.

PubMed

Lesniak, Anna; Bochynska-Czyz, Marta; Sacharczuk, Mariusz; Benhye, Sandor; Misicka, Aleksandra; Bujalska-Zadrozny, Magdalena; Lipkowski, Andrzej W

2016-06-30

The search for new drugs for cancer pain management has been a long-standing goal in basic and clinical research. Classical opioid drugs exert their primary antinociceptive effect upon activating opioid receptors located in the central nervous system. A substantial body of evidence points to the relevance of peripheral opioid receptors as potential targets for cancer pain treatment. Peptides showing limited blood-brain-barrier permeability promote peripheral analgesia in many pain models. In the present study we examined the peripheral and central analgesic effect of intravenously administered biphalin - a dimeric opioid peptide in a mouse skin cancer pain model, developed by an intraplantar inoculation of B16F0 melanoma cells. The effect of biphalin was compared with morphine - a golden standard in cancer pain management. Biphalin produced profound, dose-dependent and naloxone sensitive spinal analgesia. Additionally, the effect in the tumor-bearing paw was largely mediated by peripheral opioid receptors, as it was readily attenuated by the blood-brain-barrier-restricted opioid receptor antagonist - naloxone methiodide. On the contrary, morphine facilitated its analgesic effect primarily by activating spinal opioid receptors. Both drugs induced tolerance in B16F0 - implanted paws after chronic treatment, however biphalin as opposed to morphine, showed little decrease in its activity at the spinal level. Our results indicate that biphalin may be considered a future alternative drug in cancer pain treatment due to an enhanced local analgesic activity as well as lower tolerance liability compared with morphine. Copyright © 2016 Elsevier B.V. All rights reserved.

Stimulating effect of thyroid hormones in peripheral nerve regeneration: research history and future direction toward clinical therapy

PubMed Central

Barakat-Walter, I.; Kraftsik, R.

2018-01-01

Injury to peripheral nerves is often observed in the clinic and severe injuries may cause loss of motor and sensory functions. Despite extensive investigation, testing various surgical repair techniques and neurotrophic molecules, at present, a satisfactory method to ensuring successful recovery does not exist. For successful molecular therapy in nerve regeneration, it is essential to improve the intrinsic ability of neurons to survive and to increase the speed of axonal outgrowth. Also to induce Schwann cell phenotypical changes to prepare the local environment favorable for axonal regeneration and myelination. Therefore, any molecule that regulates gene expression of both neurons and Schwann cells could play a crucial role in peripheral nerve regeneration. Clinical and experimental studies have reported that thyroid hormones are essential for the normal development and function of the nervous system, so they could be candidates for nervous system regeneration. This review provides an overview of studies devoted to testing the effect of thyroid hormones on peripheral nerve regeneration. Also it emphasizes the importance of combining biodegradable tubes with local administration of triiodothyronine for future clinical therapy of human severe injured nerves. We highlight that the local and single administration of triiodothyronine within biodegradable nerve guide improves significantly the regeneration of severed peripheral nerves, and accelerates functional recovering. This technique provides a serious step towards future clinical application of triiodothyronine in human severe injured nerves. The possible regulatory mechanism by which triiodothyronine stimulates peripheral nerve regeneration is a rapid action on both axotomized neurons and Schwann cells. PMID:29722302

Catalytic antibodies to amyloid beta peptide in defense against Alzheimer disease.

PubMed

Taguchi, Hiroaki; Planque, Stephanie; Nishiyama, Yasuhiro; Szabo, Paul; Weksler, Marc E; Friedland, Robert P; Paul, Sudhir

2008-05-01

Immunoglobulins (Igs) that bind amyloid beta peptide (Abeta) are under clinical trials for immunotherapy of Alzheimer disease (AD). We have identified IgMs and recombinant Ig fragments that hydrolyze Abeta. Hydrolysis of peripheral Abeta by the IgMs may induce increased Abeta release from the brain. The catalytic IgMs are increased in AD patients, presumably reflecting a protective autoimmune response. Reduced Abeta aggregation and neurotoxicity attributable to the catalytic function were evident. These findings provide a foundation for development of catalytic Igs for AD immunotherapy.

Approaches to drug therapy for COPD in Russia: a proposed therapeutic algorithm.

PubMed

Zykov, Kirill A; Ovcharenko, Svetlana I

2017-01-01

Until recently, there have been few clinical algorithms for the management of patients with COPD. Current evidence-based clinical management guidelines can appear to be complex, and they lack clear step-by-step instructions. For these reasons, we chose to create a simple and practical clinical algorithm for the management of patients with COPD, which would be applicable to real-world clinical practice, and which was based on clinical symptoms and spirometric parameters that would take into account the pathophysiological heterogeneity of COPD. This optimized algorithm has two main fields, one for nonspecialist treatment by primary care and general physicians and the other for treatment by specialized pulmonologists. Patients with COPD are treated with long-acting bronchodilators and short-acting drugs on a demand basis. If the forced expiratory volume in one second (FEV 1 ) is ≥50% of predicted and symptoms are mild, treatment with a single long-acting muscarinic antagonist or long-acting beta-agonist is proposed. When FEV 1 is <50% of predicted and/or the COPD assessment test score is ≥10, the use of combined bronchodilators is advised. If there is no response to treatment after three months, referral to a pulmonary specialist is recommended for pathophysiological endotyping: 1) eosinophilic endotype with peripheral blood or sputum eosinophilia >3%; 2) neutrophilic endotype with peripheral blood neutrophilia >60% or green sputum; or 3) pauci-granulocytic endotype. It is hoped that this simple, optimized, step-by-step algorithm will help to individualize the treatment of COPD in real-world clinical practice. This algorithm has yet to be evaluated prospectively or by comparison with other COPD management algorithms, including its effects on patient treatment outcomes. However, it is hoped that this algorithm may be useful in daily clinical practice for physicians treating patients with COPD in Russia.

Preservative-free 0.9% sodium chloride for flushing and locking peripheral intravenous access device: a prospective controlled trial.

PubMed

Wang, Rui; Luo, Ou; He, Liu; Li, Jia-Xin; Zhang, Ming-Guang

2012-11-01

In Mainland China, heparin saline solution is commonly used for flushing and locking peripheral intravenous access devices in clinical practice for a long time. We conducted a prospective controlled trial to compare the effectiveness and safety of preservative-free 0.9% sodium chloride solution versus heparin saline solution as flushing and locking solution for peripheral intravenous access devices. Patients with gastroenterological or hepatic diseases were enrolled for this study from August 2011 to October 2011. After non-randomized allocation, preservative-free 0.9% sodium chloride was used as flushing and locking solution in the sodium chloride solution group, while hepatic solution (10 U/mL) was given in the heparin saline solution group. The device related complications and its maintenance duration were compared between two groups. One-way ANOVA, Chi(2), or Mantel-Haenszel test were performed using SPSS 13.0 and RevMan 5.0. Totally, 181 and 178 peripheral intravenous access devices in the sodium chloride solution and heparin saline solution groups were included and analyzed. Results indicated than sodium chloride solution did not increase the risks of occlusion (7.7% vs. 7.9%) and other adverse events of peripheral intravenous access devices (P = 0.163). Sodium chloride solution neither shortened the duration of peripheral intravenous access devices maintenance (3.6 ± 1.1 days vs. 3.7 ± 1.2 days, P = 0.651), nor increased the proportion of abnormal withdrawal (29.3% vs. 31.5%, P = 0.654). Sodium chloride solution is as effective and safe as conventional heparin saline solution for flushing and locking peripheral intravenous access devices, which results from our evidence-based study and should be transferred to other nurses in China. © 2012 Wiley Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

The effect of hypnosis on pain and peripheral blood flow in sickle-cell disease: a pilot study

PubMed Central

Bhatt, Ravi R; Martin, Sarah R; Evans, Subhadra; Lung, Kirsten; Coates, Thomas D; Zeltzer, Lonnie K; Tsao, Jennie C

2017-01-01

Background Vaso-occlusive pain crises (VOCs) are the “hallmark” of sickle-cell disease (SCD) and can lead to sympathetic nervous system dysfunction. Increased sympathetic nervous system activation during VOCs and/or pain can result in vasoconstriction, which may increase the risk for subsequent VOCs and pain. Hypnosis is a neuromodulatory intervention that may attenuate vascular and pain responsiveness. Due to the lack of laboratory-controlled pain studies in patients with SCD and healthy controls, the specific effects of hypnosis on acute pain-associated vascular responses are unknown. The current study assessed the effects of hypnosis on peripheral blood flow, pain threshold, tolerance, and intensity in adults with and without SCD. Subjects and methods Fourteen patients with SCD and 14 healthy controls were included. Participants underwent three laboratory pain tasks before and during a 30-minute hypnosis session. Peripheral blood flow, pain threshold, tolerance, and intensity before and during hypnosis were examined. Results A single 30-minute hypnosis session decreased pain intensity by a moderate amount in patients with SCD. Pain threshold and tolerance increased following hypnosis in the control group, but not in patients with SCD. Patients with SCD exhibited lower baseline peripheral blood flow and a greater increase in blood flow following hypnosis than controls. Conclusion Given that peripheral vasoconstriction plays a role in the development of VOC, current findings provide support for further laboratory and clinical investigations of the effects of cognitive–behavioral neuromodulatory interventions on pain responses and peripheral vascular flow in patients with SCD. Current results suggest that hypnosis may increase peripheral vasodilation during both the anticipation and experience of pain in patients with SCD. These findings indicate a need for further examination of the effects of hypnosis on pain and vascular responses utilizing a randomized controlled trial design. Further evidence may help determine unique effects of hypnosis and potential benefits of integrating cognitive–behavioral neuromodulatory interventions into SCD treatment. PMID:28769584

Acute Unilateral Vestibular Failure Does Not Cause Spatial Hemineglect.

PubMed

Conrad, Julian; Habs, Maximilian; Brandt, Thomas; Dieterich, Marianne

2015-01-01

Visuo-spatial neglect and vestibular disorders have common clinical findings and involve the same cortical areas. We questioned (1) whether visuo-spatial hemineglect is not only a disorder of spatial attention but may also reflect a disorder of higher cortical vestibular function and (2) whether a vestibular tone imbalance due to an acute peripheral dysfunction can also cause symptoms of neglect or extinction. Therefore, patients with an acute unilateral peripheral vestibular failure (VF) were tested for symptoms of hemineglect. Twenty-eight patients with acute VF were assessed for signs of vestibular deficits and spatial neglect using clinical measures and various common standardized paper-pencil tests. Neglect severity was evaluated further with the Center of Cancellation method. Pathological neglect test scores were correlated with the degree of vestibular dysfunction determined by the subjective visual vertical and caloric testing. Three patients showed isolated pathological scores in one or the other neglect test, either ipsilesionally or contralesionally to the VF. None of the patients fulfilled the diagnostic criteria of spatial hemineglect or extinction. A vestibular tone imbalance due to unilateral failure of the vestibular endorgan does not cause spatial hemineglect, but evidence indicates it causes mild attentional deficits in both visual hemifields.

Acute Unilateral Vestibular Failure Does Not Cause Spatial Hemineglect

PubMed Central

Conrad, Julian; Habs, Maximilian; Brandt, Thomas; Dieterich, Marianne

2015-01-01

Objectives Visuo-spatial neglect and vestibular disorders have common clinical findings and involve the same cortical areas. We questioned (1) whether visuo-spatial hemineglect is not only a disorder of spatial attention but may also reflect a disorder of higher cortical vestibular function and (2) whether a vestibular tone imbalance due to an acute peripheral dysfunction can also cause symptoms of neglect or extinction. Therefore, patients with an acute unilateral peripheral vestibular failure (VF) were tested for symptoms of hemineglect. Methods Twenty-eight patients with acute VF were assessed for signs of vestibular deficits and spatial neglect using clinical measures and various common standardized paper-pencil tests. Neglect severity was evaluated further with the Center of Cancellation method. Pathological neglect test scores were correlated with the degree of vestibular dysfunction determined by the subjective visual vertical and caloric testing. Results Three patients showed isolated pathological scores in one or the other neglect test, either ipsilesionally or contralesionally to the VF. None of the patients fulfilled the diagnostic criteria of spatial hemineglect or extinction. Conclusions A vestibular tone imbalance due to unilateral failure of the vestibular endorgan does not cause spatial hemineglect, but evidence indicates it causes mild attentional deficits in both visual hemifields. PMID:26247469

Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve Repair and Functional Outcomes

DTIC Science & Technology

2017-07-01

AWARD NUMBER: W81XWH-15-2-0026 TITLE: Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve...of Decellularized Nerve Allograft with 5a. CONTRACT NUMBER Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve 5b. GRANT NUMBER W81XWH...commercially available decellularized processed peripheral nerve allograft scaffold (Avance® Nerve Graft, AxoGen, Alachua FL) with autologous bone marrow

Peripheral Frequency of CD4+ CD28− Cells in Acute Ischemic Stroke

PubMed Central

Tuttolomondo, Antonino; Pecoraro, Rosaria; Casuccio, Alessandra; Di Raimondo, Domenico; Buttà, Carmelo; Clemente, Giuseppe; Corte, Vittoriano della; Guggino, Giuliana; Arnao, Valentina; Maida, Carlo; Simonetta, Irene; Maugeri, Rosario; Squatrito, Rosario; Pinto, Antonio

2015-01-01

Abstract CD4+ CD28− T cells also called CD28 null cells have been reported as increased in the clinical setting of acute coronary syndrome. Only 2 studies previously analyzed peripheral frequency of CD28 null cells in subjects with acute ischemic stroke but, to our knowledge, peripheral frequency of CD28 null cells in each TOAST subtype of ischemic stroke has never been evaluated. We hypothesized that CD4+ cells and, in particular, the CD28 null cell subset could show a different degree of peripheral percentage in subjects with acute ischemic stroke in relation to clinical subtype and severity of ischemic stroke. The aim of our study was to analyze peripheral frequency of CD28 null cells in subjects with acute ischemic stroke in relation to TOAST diagnostic subtype, and to evaluate their relationship with scores of clinical severity of acute ischemic stroke, and their predictive role in the diagnosis of acute ischemic stroke and diagnostic subtype We enrolled 98 consecutive subjects admitted to our recruitment wards with a diagnosis of ischemic stroke. As controls we enrolled 66 hospitalized patients without a diagnosis of acute ischemic stroke. Peripheral frequency of CD4+ and CD28 null cells has been evaluated with a FACS Calibur flow cytometer. Subjects with acute ischemic stroke had a significantly higher peripheral frequency of CD4+ cells and CD28 null cells compared to control subjects without acute ischemic stroke. Subjects with cardioembolic stroke had a significantly higher peripheral frequency of CD4+ cells and CD28 null cells compared to subjects with other TOAST subtypes. We observed a significant relationship between CD28 null cells peripheral percentage and Scandinavian Stroke Scale and NIHSS scores. ROC curve analysis showed that CD28 null cell percentage may be useful to differentiate between stroke subtypes. These findings seem suggest a possible role for a T-cell component also in acute ischemic stroke clinical setting showing a different peripheral frequency of CD28 null cells in relation of each TOAST subtype of stroke. PMID:25997053

Dexamethasone as an adjuvant to peripheral nerve block.

PubMed

Pehora, Carolyne; Pearson, Annabel Me; Kaushal, Alka; Crawford, Mark W; Johnston, Bradley

2017-11-09

Peripheral nerve block (infiltration of local anaesthetic around a nerve) is used for anaesthesia or analgesia. A limitation to its use for postoperative analgesia is that the analgesic effect lasts only a few hours, after which moderate to severe pain at the surgical site may result in the need for alternative analgesic therapy. Several adjuvants have been used to prolong the analgesic duration of peripheral nerve block, including perineural or intravenous dexamethasone. To evaluate the comparative efficacy and safety of perineural dexamethasone versus placebo, intravenous dexamethasone versus placebo, and perineural dexamethasone versus intravenous dexamethasone when added to peripheral nerve block for postoperative pain control in people undergoing surgery. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, DARE, Web of Science and Scopus from inception to 25 April 2017. We also searched trial registry databases, Google Scholar and meeting abstracts from the American Society of Anesthesiologists, the Canadian Anesthesiologists' Society, the American Society of Regional Anesthesia, and the European Society of Regional Anaesthesia. We included all randomized controlled trials (RCTs) comparing perineural dexamethasone with placebo, intravenous dexamethasone with placebo, or perineural dexamethasone with intravenous dexamethasone in participants receiving peripheral nerve block for upper or lower limb surgery. We used standard methodological procedures expected by Cochrane. We included 35 trials of 2702 participants aged 15 to 78 years; 33 studies enrolled participants undergoing upper limb surgery and two undergoing lower limb surgery. Risk of bias was low in 13 studies and high/unclear in 22. Perineural dexamethasone versus placeboDuration of sensory block was significantly longer in the perineural dexamethasone group compared with placebo (mean difference (MD) 6.70 hours, 95% confidence interval (CI) 5.54 to 7.85; participants1625; studies 27). Postoperative pain intensity at 12 and 24 hours was significantly lower in the perineural dexamethasone group compared with control (MD -2.08, 95% CI -2.63 to -1.53; participants 257; studies 5) and (MD -1.63, 95% CI -2.34 to -0.93; participants 469; studies 9), respectively. There was no significant difference at 48 hours (MD -0.61, 95% CI -1.24 to 0.03; participants 296; studies 4). The quality of evidence is very low for postoperative pain intensity at 12 hours and low for the remaining outcomes. Cumulative 24-hour postoperative opioid consumption was significantly lower in the perineural dexamethasone group compared with placebo (MD 19.25 mg, 95% CI 5.99 to 32.51; participants 380; studies 6). Intravenous dexamethasone versus placeboDuration of sensory block was significantly longer in the intravenous dexamethasone group compared with placebo (MD 6.21, 95% CI 3.53 to 8.88; participants 499; studies 8). Postoperative pain intensity at 12 and 24 hours was significantly lower in the intravenous dexamethasone group compared with placebo (MD -1.24, 95% CI -2.44 to -0.04; participants 162; studies 3) and (MD -1.26, 95% CI -2.23 to -0.29; participants 257; studies 5), respectively. There was no significant difference at 48 hours (MD -0.21, 95% CI -0.83 to 0.41; participants 172; studies 3). The quality of evidence is moderate for duration of sensory block and postoperative pain intensity at 24 hours, and low for the remaining outcomes. Cumulative 24-hour postoperative opioid consumption was significantly lower in the intravenous dexamethasone group compared with placebo (MD -6.58 mg, 95% CI -10.56 to -2.60; participants 287; studies 5). Perinerual versus intravenous dexamethasoneDuration of sensory block was significantly longer in the perineural dexamethasone group compared with intravenous by three hours (MD 3.14 hours, 95% CI 1.68 to 4.59; participants 720; studies 9). We found that postoperative pain intensity at 12 hours and 24 hours was significantly lower in the perineural dexamethasone group compared with intravenous, however, the MD did not surpass our pre-determined minimally important difference of 1.2 on the Visual Analgue Scale/Numerical Rating Scale, therefore the results are not clinically significant (MD -1.01, 95% CI -1.51 to -0.50; participants 217; studies 3) and (MD -0.77, 95% CI -1.47 to -0.08; participants 309; studies 5), respectively. There was no significant difference in severity of postoperative pain at 48 hours (MD 0.13, 95% CI -0.35 to 0.61; participants 227; studies 3). The quality of evidence is moderate for duration of sensory block and postoperative pain intensity at 24 hours, and low for the remaining outcomes. There was no difference in cumulative postoperative 24-hour opioid consumption (MD -3.87 mg, 95% CI -9.93 to 2.19; participants 242; studies 4). Incidence of severe adverse eventsFive serious adverse events were reported. One block-related event (pneumothorax) occurred in one participant in a trial comparing perineural dexamethasone and placebo; however group allocation was not reported. Four non-block-related events occurred in two trials comparing perineural dexamethasone, intravenous dexamethasone and placebo. Two participants in the placebo group required hospitalization within one week of surgery; one for a fall and one for a bowel infection. One participant in the placebo group developed Complex Regional Pain Syndrome Type I and one in the intravenous dexamethasone group developed pneumonia. The quality of evidence is very low due to the sparse number of events. Low- to moderate-quality evidence suggests that when used as an adjuvant to peripheral nerve block in upper limb surgery, both perineural and intravenous dexamethasone may prolong duration of sensory block and are effective in reducing postoperative pain intensity and opioid consumption. There is not enough evidence to determine the effectiveness of dexamethasone as an adjuvant to peripheral nerve block in lower limb surgeries and there is no evidence in children. The results of our review may not apply to participants at risk of dexamethasone-related adverse events for whom clinical trials would probably be unsafe.There is not enough evidence to determine the effectiveness of dexamethasone as an adjuvant to peripheral nerve block in lower limb surgeries and there is no evidence in children. The results of our review may not be apply to participants who at risk of dexamethasone-related adverse events for whom clinical trials would probably be unsafe. The nine ongoing trials registered at ClinicalTrials.gov may change the results of this review.

The Effect of Highlighting on Processing and Memory of Central and Peripheral Text Information: Evidence from Eye Movements

ERIC Educational Resources Information Center

Yeari, Menahem; Oudega, Marja; van den Broek, Paul

2017-01-01

The present study investigated the effect of text highlighting on online processing and memory of central and peripheral information. We compared processing time (using eye-tracking methodology) and recall of central and peripheral information for three types of highlighting: (a) highlighting of central information, (b) highlighting of peripheral…

High Prevalence and Incidence of Diabetic Peripheral Neuropathy in Children and Adolescents With Type 1 Diabetes Mellitus: Results From a Five-Year Prospective Cohort Study.

PubMed

Walter-Höliner, Isabella; Barbarini, Daniela Seick; Lütschg, Jürg; Blassnig-Ezeh, Anya; Zanier, Ulrike; Saely, Christoph H; Simma, Burkhard

2018-03-01

In this prospective cohort study, we investigated the prevalence of diabetic peripheral neuropathy at baseline and after five years of follow-up in children and adolescents with type 1 diabetes mellitus using both measurements of nerve conduction velocity and clinical neurological examination. A total of 38 patients who underwent insulin pump or intensive insulin therapy were included. The subjects averaged 12.6 ± 2.4 years of age and their diabetes duration averaged 5.6 ± 3.2 years. All patients underwent a detailed physical, neurological, and electrophysiological examination, as well as laboratory testing at their annual checkup. At baseline, the prevalence of diabetic peripheral neuropathy diagnosed using neurological examination was 13.2%, whereas nerve conduction velocity testing revealed diabetic peripheral neuropathy in 31.6%, highlighting a high prevalence of subclinical diabetic peripheral neuropathy. During follow-up, there was a strong increase in the prevalence of clinically diagnosed diabetic peripheral neuropathy, which reached 34.2% (P = 0.039) after five years; the proportion of patients with subclinical diabetic peripheral neuropathy even reached 63.2% (P = 0.002). The most significant changes in electrophysiological parameters were observed in the tibial sensory nerve (P = 0.001). The prevalence of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus was high, and there was a rapid increase in the prevalence of diabetic peripheral neuropathy during a five-year follow-up interval. Importantly, our data show that a mere clinical evaluation is not sensitive enough to diagnose diabetic peripheral neuropathy in these patients. Nerve conduction velocity measurement, which is regarded as the gold standard for the assessment of diabetic peripheral neuropathy, should be applied more broadly. Copyright © 2017 Elsevier Inc. All rights reserved.

Standing Balance and Trunk Position Sense in Impaired Glucose Tolerance (IGT)-Related Peripheral Neuropathy

PubMed Central

Goldberg, Allon; Russell, James William; Alexander, Neil Burton

2009-01-01

Type 2 diabetes mellitus (T2DM) and pre-diabetes or impaired glucose tolerance (IGT) affects a large segment of the population. Peripheral neuropathy (PN) is a common complication of T2DM, leading to sensory and motor deficits. While T2DM-related PN often results in balance- and mobility-related dysfunction which manifests as gait instability and falls, little is known about balance capabilities in patients who have evidence of PN related to IGT (IGT-PN). We evaluated patients with IGT-PN on commonly-used clinical balance and mobility tests as well as a new test of trunk position sense and balance impairment, trunk repositioning errors (TREs). Eight participants aged 50–72 years with IGT-PN, and eight age and gender matched controls underwent balance, mobility and trunk repositioning accuracy tests at a university neurology clinic and mobility research laboratory. Compared to controls, IGT-PN participants had as much as twice the magnitude of TREs and stood approximately half as long on the single leg balance test. People with IGT-PN exhibit deficits in standing balance and trunk position sense. Furthermore, there was a significant association between performance on commonly-used clinical balance and mobility tests, and electrophysiological and clinical measures of neuropathy in IGT-PN participants. Because IGT-related neuropathy represents the earliest stage of diabetic neuropathy, deficits in IGT-PN participants highlights the importance of early screening in the dysglycemic process for neuropathy and associated balance deficits. PMID:18439624

A review of the clinical utility of duloxetine in the treatment of diabetic peripheral neuropathic pain

PubMed Central

King, Jordan B; Schauerhamer, Marisa B; Bellows, Brandon K

2015-01-01

Diabetes mellitus is a world-wide epidemic with many long-term complications, with neuropathy being the most common. In particular, diabetic peripheral neuropathic pain (DPNP), can be one of the most distressing complications associated with diabetes, leading to decreases in physical and mental quality of life. Despite the availability of many efficient medications, DPNP remains a challenge to treat, and the optimal sequencing of pharmacotherapy remains unknown. Currently, there are only three medications approved by the US Food and Drug Administration specifically for the management of DPNP. Duloxetine (DUL), a selective serotonin-norepinephrine reuptake inhibitor, is one of these. With the goal of optimizing pharmacotherapy use in DPNP population, a review of current literature was conducted, and the clinical utility of DUL described. Along with early clinical trials, recently published observational studies and pharmacoeconomic models may be useful in guiding decision making by clinicians and managed care organizations. In real-world practice settings, DUL is associated with decreased or similar opioid utilization, increased medication adherence, and similar health care costs compared with current standard of care. DUL has consistently been found to be a cost-effective option over short time-horizons. Currently, the long-term cost-effectiveness of DUL is unknown. Evidence derived from randomized clinical trials, real-world observations, and economic models support the use of DUL as a first-line treatment option from the perspective of the patient, clinician, and managed care payer. PMID:26309404

A review of the clinical utility of duloxetine in the treatment of diabetic peripheral neuropathic pain.

PubMed

King, Jordan B; Schauerhamer, Marisa B; Bellows, Brandon K

2015-01-01

Diabetes mellitus is a world-wide epidemic with many long-term complications, with neuropathy being the most common. In particular, diabetic peripheral neuropathic pain (DPNP), can be one of the most distressing complications associated with diabetes, leading to decreases in physical and mental quality of life. Despite the availability of many efficient medications, DPNP remains a challenge to treat, and the optimal sequencing of pharmacotherapy remains unknown. Currently, there are only three medications approved by the US Food and Drug Administration specifically for the management of DPNP. Duloxetine (DUL), a selective serotonin-norepinephrine reuptake inhibitor, is one of these. With the goal of optimizing pharmacotherapy use in DPNP population, a review of current literature was conducted, and the clinical utility of DUL described. Along with early clinical trials, recently published observational studies and pharmacoeconomic models may be useful in guiding decision making by clinicians and managed care organizations. In real-world practice settings, DUL is associated with decreased or similar opioid utilization, increased medication adherence, and similar health care costs compared with current standard of care. DUL has consistently been found to be a cost-effective option over short time-horizons. Currently, the long-term cost-effectiveness of DUL is unknown. Evidence derived from randomized clinical trials, real-world observations, and economic models support the use of DUL as a first-line treatment option from the perspective of the patient, clinician, and managed care payer.

The topical 5% lidocaine medicated plaster in localized neuropathic pain: a reappraisal of the clinical evidence

PubMed Central

de León-Casasola, Oscar A; Mayoral, Victor

2016-01-01

Topical 5% lidocaine medicated plasters represent a well-established first-line option for the treatment of peripheral localized neuropathic pain (LNP). This review provides an updated overview of the clinical evidence (randomized, controlled, and open-label clinical studies, real-life daily clinical practice, and case series). The 5% lidocaine medicated plaster effectively provides pain relief in postherpetic neuralgia, and data from a large open-label controlled study indicate that the 5% lidocaine medicated plaster is as effective as systemic pregabalin in postherpetic neuralgia and painful diabetic polyneuropathy but with an improved tolerability profile. Additionally, improved analgesia and fewer side effects were experienced by patients treated synchronously with the 5% lidocaine medicated plaster, further demonstrating the value of multimodal analgesia in LNP. The 5% lidocaine medicated plaster provides continued benefit after long-term (≤7 years) use and is also effective in various other LNP conditions. Minor application-site reactions are the most common adverse events associated with the 5% lidocaine medicated plaster; there is minimal risk of systemic adverse events and drug–drug interactions. Although further well-controlled studies are warranted, the 5% lidocaine medicated plaster is efficacious and safe in LNP and may have particular clinical benefit in elderly and/or medically compromised patients because of the low incidence of adverse events. PMID:26929664

A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure

PubMed Central

Jasti, Dushyanth Babu; Mallipeddi, Sarat; Apparao, A.; Vengamma, B.; Sivakumar, V.; Kolli, Satyarao

2017-01-01

Objective: To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Materials and Methods: Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. Results: The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure (n = 100) and severe renal failure patients (n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Conclusion: Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics. PMID:29204008

Moral imperialism and multi-centric clinical trials in peripheral countries.

PubMed

Garrafa, Volnei; Lorenzo, Claudio

2008-10-01

Moral imperialism is expressed in attempts to impose moral standards from one particular culture, geopolitical region or culture onto other cultures, regions or countries. Examples of Direct Moral Imperialism can be seen in various recurrent events involving multi-centric clinical trials promoted by developed (central) countries in poor and developing (peripheral) countries, particularly projects related to the theory of double standards in research. After the WMA General Assembly refused to change the Helsinki Declaration - which would have given moral recognition to the above mentioned theory - the USA abandoned the declaration and began to promote regional seminars in peripheral countries with the aim of "training" researchers on ethical perspectives that reflect America's best interests. Individuals who received such training became transmitters of these central countries' ideas across the peripheral countries, representing a form of Indirect Moral Imperialism. The paper proposes the establishment of regulatory and social control systems for clinical trials implemented in peripheral countries, through the formulation of ethical norms that reflect the specific contexts of these countries, along with the drawing up and validation of their own national norms.

Sulfur spring dermatitis.

PubMed

Lee, Chieh-Chi; Wu, Yu-Hung

2014-11-01

Thermal sulfur baths are a form of balneotherapy promoted in many cultures for improvement of skin conditions; however, certain uncommon skin problems may occur after bathing in hot sulfur springs. We report the case of a 65-year-old man who presented with multiple confluent, punched-out, round ulcers with peripheral erythema on the thighs and shins after bathing in a hot sulfur spring. Histopathologic examination revealed homogeneous coagulation necrosis of the epidermis and papillary dermis. Tissue cultures showed no evidence of a microbial infection. The histopathologic findings and clinical course were consistent with a superficial second-degree burn. When patients present with these findings, sulfur spring dermatitis should be considered in the differential diagnosis. Moreover, the patient's clinical history is crucial for correct diagnosis.

Fatal acute babesiosis in a juvenile wild dog (Lycaon pictus).

PubMed

Colly, L P; Nesbit, J W

1992-03-01

Clinical examination of a 75-day-old captive juvenile wild dog suffering from lassitude revealed pale mucous membranes, icterus, laboured respiration, a "water-hammer" pulse and splenomegaly. A peripheral blood smear containing numerous Babesia-infected erythrocytes confirmed the diagnosis of babesiosis. Treatment was unsuccessful and the animal died shortly after receiving a blood transfusion. The findings at necropsy were typical for acute babesiosis and included anaemia, icterus, splenomegaly and haemoglobinuria. In addition, marked atrophy of the thymus and lymph nodes was evident. Microscopic and electron microscopic examination of selected tissues disclosed high parasitaemia with vascular stasis and injury to both endothelial and parenchymal components. It is speculated that vaccination-induced immune incompetence predisposed to development of clinical babesiosis.

Robot-Aided Neurorehabilitation

PubMed Central

Krebs, Hermano Igo; Hogan, Neville; Aisen, Mindy L.; Volpe, Bruce T.

2009-01-01

Our goal is to apply robotics and automation technology to assist, enhance, quantify, and document neurorehabilitation. This paper reviews a clinical trial involving 20 stroke patients with a prototype robot-aided rehabilitation facility developed at the Massachusetts Institute of Technology, Cambridge, (MIT) and tested at Burke Rehabilitation Hospital, White Plains, NY. It also presents our approach to analyze kinematic data collected in the robot-aided assessment procedure. In particular, we present evidence 1) that robot-aided therapy does not have adverse effects, 2) that patients tolerate the procedure, and 3) that peripheral manipulation of the impaired limb may influence brain recovery. These results are based on standard clinical assessment procedures. We also present one approach using kinematic data in a robot-aided assessment procedure. PMID:9535526

Nutraceuticals and chemotherapy induced peripheral neuropathy (CIPN): a systematic review.

PubMed

Schloss, Janet M; Colosimo, Maree; Airey, Caroline; Masci, Paul P; Linnane, Anthony W; Vitetta, Luis

2013-12-01

Chemotherapy induced peripheral neuropathy [CIPN] is a common significant and debilitating side effect resulting from the administration of neurotoxic chemotherapeutic agents. These pharmaco-chemotherapeutics can include taxanes, vinca alkaloids and others. Moderate to severe CIPN significantly decreases the quality of life and physical abilities of cancer patients and current pharmacotherapy for CIPN e.g. Amifostine and antidepressants have had limited efficacy and may themselves induce adverse side effects. To determine the potential use of nutraceuticals i.e. vitamin E, acetyl-L-carnitine, glutamine, glutathione, vitamin B6, omega-3 fatty acids, magnesium, calcium, alpha lipoic acid and n-acetyl cysteine as adjuvants in cancer treatments a systematic literature review was conducted. Revised clinical studies comprised of randomized clinical trials that investigated the anti-CIPN effect of nutraceuticals as the adjuvant intervention in patients administered chemotherapy. Twenty-four studies were assessed on methodological quality and limitations identified. Studies were mixed in their recommendations for nutraceuticals. Currently no agent has shown solid beneficial evidence to be recommended for the treatment or prophylaxis of CIPN. The standard of care for CIPN includes dose reduction and/or discontinuation of chemotherapy treatment. The management of CIPN remains an important challenge and future studies are warranted before recommendations for the use of supplements can be made. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Comparison the effects of two types of therapeutic exercises Frenkele vs. Swiss ball on the clinical balance measures in patients with type II diabetic neuropathy.

PubMed

Rojhani-Shirazi, Zahra; Barzintaj, Fatemeh; Salimifard, Mohamad Reza

2017-11-01

The number of diabetic patients is increasing in the world. Peripheral neuropathy is the most important problem of diabetes. Neuropathy eventually leads to balance impairment which is the main cause of falling down in these patients However, not sufficient evidences available to compare different protocols for improving balance in diabetic patients. This study aimed to compare the effects of two therapeutic exercises on clinical balance measures in patients with type II diabetic peripheral neuropathy. The study was performed on 60 patients with diabetes categorized randomly into three groups: an intervention group (N=20) that received ball training exercise, another intervention group (N=20) that received Frenkel exercise and a control group (N=20) that received no interventions. Exercise training session was performed for 3 weeks. Then, clinical balance measures were computed in the three groups. Paired t-test and one-way ANOVA were used to analyze the collected data. Both types of therapeutic exercise programs significantly improved balance in single leg stance, star excursion test, and Berg balance scale test (P˂0.05) compared to the control group. Besides, this was more significant in the ball training group (P˂0.05). To improve balance in diabetic neuropathy, Swiss ball exercise is preferred compared to Frenkel training. Copyright © 2016. Published by Elsevier Ltd.

Induction of Migraine-Like Photophobic Behavior in Mice by Both Peripheral and Central CGRP Mechanisms.

PubMed

Mason, Bianca N; Kaiser, Eric A; Kuburas, Adisa; Loomis, Maria-Cristina M; Latham, John A; Garcia-Martinez, Leon F; Russo, Andrew F

2017-01-04

The neuropeptide calcitonin gene-related peptide (CGRP) is a key player in migraine. Although migraine can be treated using CGRP antagonists that act peripherally, the relevant sites of CGRP action remain unknown. To address the role of CGRP both within and outside the CNS, we used CGRP-induced light-aversive behavior in mice as a measure of migraine-associated photophobia. Peripheral (intraperitoneal) injection of CGRP resulted in light-aversive behavior in wild-type CD1 mice similar to aversion seen previously after central (intracerebroventricular) injection. The phenotype was also observed in C57BL/6J mice, although to a lesser degree and with more variability. After intraperitoneal CGRP, motility was decreased in the dark only, similar to motility changes after intracerebroventricular CGRP. In addition, as with intracerebroventricular CGRP, there was no general increase in anxiety as measured in an open-field assay after intraperitoneal CGRP. Importantly, two clinically effective migraine drugs, the 5-HT 1B/D agonist sumatriptan and a CGRP-blocking monoclonal antibody, attenuated the peripheral CGRP-induced light aversion and motility behaviors. To begin to address the mechanism of peripheral CGRP action, we used transgenic CGRP-sensitized mice that have elevated levels of the CGRP receptor hRAMP1 subunit in nervous tissue (nestin/hRAMP1). Surprisingly, sensitivity to low light was not seen after intraperitoneal CGRP injection, but was seen after intracerebroventricular CGRP injection. These results suggest that CGRP can act in both the periphery and the brain by distinct mechanisms and that CGRP actions may be transmitted to the CNS via indirect sensitization of peripheral nerves. The neuropeptide calcitonin gene-related peptide (CGRP) is a central player in migraine pathogenesis, yet its site(s) of action remains unknown. Some preclinical studies have pointed to central sites in the brain and brainstem. However, a peripheral site of action is indicated by the ability of intravenous CGRP to trigger migraine in humans and the efficacy of CGRP receptor antagonists that evidently do no penetrate the CNS in effective amounts. Resolving this issue is particularly important given recent clinical trials showing that anti-CGRP monoclonal antibodies can reduce and even prevent migraine attacks. In this study, we report that CGRP can act in both the brain and the periphery of the mouse to cause migraine-like photophobia by apparently distinct mechanisms. Copyright © 2017 the authors 0270-6474/17/370204-13$15.00/0.

Prostate specific antigen and acinar density: a new dimension, the "Prostatocrit".

PubMed

Robinson, Simon; Laniado, Marc; Montgomery, Bruce

2017-01-01

Prostate-specific antigen densities have limited success in diagnosing prostate cancer. We emphasise the importance of the peripheral zone when considered with its cellular constituents, the "prostatocrit". Using zonal volumes and asymmetry of glandular acini, we generate a peripheral zone acinar volume and density. With the ratio to the whole gland, we can better predict high grade and all grade cancer. We can model the gland into its acinar and stromal elements. This new "prostatocrit" model could offer more accurate nomograms for biopsy. 674 patients underwent TRUS and biopsy. Whole gland and zonal volumes were recorded. We compared ratio and acinar volumes when added to a "clinic" model using traditional PSA density. Univariate logistic regression was used to find significant predictors for all and high grade cancer. Backwards multiple logistic regression was used to generate ROC curves comparing the new model to conventional density and PSA alone. Prediction of all grades of prostate cancer: significant variables revealed four significant "prostatocrit" parameters: log peripheral zone acinar density; peripheral zone acinar volume/whole gland acinar volume; peripheral zone acinar density/whole gland volume; peripheral zone acinar density. Acinar model (AUC 0.774), clinic model (AUC 0.745) (P=0.0105). Prediction of high grade prostate cancer: peripheral zone acinar density ("prostatocrit") was the only significant density predictor. Acinar model (AUC 0.811), clinic model (AUC 0.769) (P=0.0005). There is renewed use for ratio and "prostatocrit" density of the peripheral zone in predicting cancer. This outperforms all traditional density measurements. Copyright® by the International Brazilian Journal of Urology.

Liposomal bupivacaine peripheral nerve block for the management of postoperative pain.

PubMed

Hamilton, Thomas W; Athanassoglou, Vassilis; Trivella, Marialena; Strickland, Louise H; Mellon, Stephen; Murray, David; Pandit, Hemant G

2016-08-25

Postoperative pain remains a significant issue with poor perioperative pain management associated with an increased risk of morbidity and mortality. Liposomal bupivacaine is an analgesic consisting of bupivacaine hydrochloride encapsulated within multiple, non-concentric lipid bi-layers offering a novel method of sustained release. To assess the analgesic efficacy and adverse effects of liposomal bupivacaine infiltration peripheral nerve block for the management of postoperative pain. We identified randomised trials of liposomal bupivacaine peripheral nerve block for the management of postoperative pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 1), Ovid MEDLINE (1946 to January Week 1 2016), Ovid MEDLINE In-Process (14 January 2016), EMBASE (1974 to 13 January 2016), ISI Web of Science (1945 to 14 January 2016), and reference lists of retrieved articles. We sought unpublished studies from Internet sources, and searched clinical trials databases for ongoing trials. The date of the most recent search was 15 January 2016. Randomised, double-blind, placebo- or active-controlled clinical trials of a single dose of liposomal bupivacaine administered as a peripheral nerve block in adults aged 18 years or over undergoing elective surgery at any surgical site. We included trials if they had at least two comparison groups for liposomal bupivacaine peripheral nerve block compared with placebo or other types of analgesia. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We performed analyses using standard statistical techniques as described in the Cochrane Handbook for Systematic Reviews of Interventions, using Review Manager 5. We planned to perform a meta-analysis, however there were insufficient data to ensure a clinically meaningful answer; as such we have produced a 'Summary of findings' table in a narrative format, and where possible we assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). We identified seven studies that met inclusion criteria for this review. Three were recorded as completed (or terminated) but no results were published. Of the remaining four studies (299 participants): two investigated liposomal bupivacaine transversus abdominis plane (TAP) block, one liposomal bupivacaine dorsal penile nerve block, and one ankle block. The study investigating liposomal bupivacaine ankle block was a Phase II dose-escalating/de-escalating trial presenting pooled data that we could not use in our analysis.The studies did not report our primary outcome, cumulative pain score between 0 and 72 hours, and secondary outcomes, mean pain score at 12, 24, 48, 72, or 96 hours. One study reported no difference in mean pain score during the first, second, and third postoperative 24-hour periods in participants receiving liposomal bupivacaine TAP block compared to no TAP block. Two studies, both in people undergoing laparoscopic surgery under TAP block, investigated cumulative postoperative opioid dose, reported opposing findings. One found a lower cumulative opioid consumption between 0 and 72 hours compared to bupivacaine hydrochloride TAP block and one found no difference during the first, second, and third postoperative 24-hour periods compared to no TAP block. No studies reported time to first postoperative opioid or percentage not requiring opioids over the initial 72 hours. No studies reported a health economic analysis or patient-reported outcome measures (outside of pain). The review authors sought data regarding adverse events but none were available, however there were no withdrawals reported to be due to adverse events.Using GRADE, we considered the quality of evidence to be very low with any estimate of effect very uncertain and further research very likely to have an important impact on our confidence in the estimate of effect. All studies were at high risk of bias due to their small sample size (fewer than 50 participants per arm) leading to uncertainty around effect estimates. Additionally, inconsistency of results and sparseness of data resulted in further downgrading of the quality of the data. A lack of evidence has prevented an assessment of the efficacy of liposomal bupivacaine administered as a peripheral nerve block. At present there is a lack of data to support or refute the use of liposomal bupivacaine administered as a peripheral nerve block for the management of postoperative pain. Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Chronic peripheral inflammation, hippocampal neurogenesis, and behavior.

PubMed

Chesnokova, Vera; Pechnick, Robert N; Wawrowsky, Kolja

2016-11-01

Adult hippocampal neurogenesis is involved in memory and learning, and disrupted neurogenesis is implicated in cognitive impairment and mood disorders, including anxiety and depression. Some long-term peripheral illnesses and metabolic disorders, as well as normal aging, create a state of chronic peripheral inflammation. These conditions are associated with behavioral disturbances linked to disrupted adult hippocampal neurogenesis, such as cognitive impairment, deficits in learning and memory, and depression and anxiety. Pro-inflammatory cytokines released in the periphery are involved in peripheral immune system-to-brain communication by activating resident microglia in the brain. Activated microglia reduce neurogenesis by suppressing neuronal stem cell proliferation, increasing apoptosis of neuronal progenitor cells, and decreasing survival of newly developing neurons and their integration into existing neuronal circuits. In this review, we summarize evolving evidence that the state of chronic peripheral inflammation reduces adult hippocampal neurogenesis, which, in turn, produces the behavioral disturbances observed in chronic inflammatory disorders. As there are no data available on neurogenesis in humans with chronic peripheral inflammatory disease, we focus on animal models and, in parallel, consider the evidence of cognitive disturbance and mood disorders in human patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of high iron intake on cognition and neurodegeneration in humans and in animal models: a systematic review

PubMed Central

Agrawal, Sonal; Berggren, Kiersten L.; Marks, Eileen; Fox, Jonathan H.

2017-01-01

Abstract Context Accumulation of brain iron is linked to aging and protein-misfolding neurodegenerative diseases. High iron intake may influence important brain health outcomes in later life. Objective The aim of this systematic review was to examine evidence from animal and human studies of the effects of high iron intake or peripheral iron status on adult cognition, brain aging, and neurodegeneration. Data Sources MEDLINE, Scopus, CAB Abstracts, the Cochrane Central Register of Clinical Trials, and OpenGrey databases were searched. Study Selection Studies investigating the effect of elevated iron intake at all postnatal life stages in mammalian models and humans on measures of adult brain health were included. Data Extraction Data were extracted and evaluated by two authors independently, with discrepancies resolved by discussion. Neurodegenerative disease diagnosis and/or behavioral/cognitive, biochemical, and brain morphologic findings were used to study the effects of iron intake or peripheral iron status on brain health. Risk of bias was assessed for animal and human studies. PRISMA guidelines for reporting systematic reviews were followed. Results Thirty-four preclinical and 14 clinical studies were identified from database searches. Thirty-three preclinical studies provided evidence supporting an adverse effect of nutritionally relevant high iron intake in neonates on brain-health-related outcomes in adults. Human studies varied considerably in design, quality, and findings; none investigated the effects of high iron intake in neonates/infants. Conclusions Human studies are needed to verify whether dietary iron intake levels used in neonates/infants to prevent iron deficiency have effects on brain aging and neurodegenerative disease outcomes. PMID:28505363

Performance of the ASAS classification criteria for axial and peripheral spondyloarthritis: a systematic literature review and meta-analysis.

PubMed

Sepriano, Alexandre; Rubio, Roxana; Ramiro, Sofia; Landewé, Robert; van der Heijde, Désirée

2017-05-01

To summarise the evidence on the performance of the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA) (also imaging and clinical arm separately), peripheral (p)SpA and the entire set, when tested against the rheumatologist's diagnosis ('reference standard'). A systematic literature review was performed to identify eligible studies. Raw data on SpA diagnosis and classification were extracted or, if necessary, obtained from the authors of the selected publications. A meta-analysis was performed to obtain pooled estimates for sensitivity, specificity, positive and negative likelihood ratios, by fitting random effects models. Nine papers fulfilled the inclusion criteria (N=5739 patients). The entire set of the ASAS SpA criteria yielded a high pooled sensitivity (73%) and specificity (88%). Similarly, good results were found for the axSpA criteria (sensitivity: 82%; specificity: 88%). Splitting the axSpA criteria in 'imaging arm only' and 'clinical arm only' resulted in much lower sensitivity (30% and 23% respectively), but very high specificity was retained (97% and 94% respectively). The pSpA criteria were less often tested than the axSpA criteria and showed a similarly high pooled specificity (87%) but lower sensitivity (63%). Accumulated evidence from studies with more than 5500 patients confirms the good performance of the various ASAS SpA criteria as tested against the rheumatologist's diagnosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Between genetics and biology. Is ENMG useful in peripheral neuropathy diagnosis and management?

PubMed

Stålberg, E

2016-10-01

Neurography and EMG are complementary techniques used in the diagnosis and monitoring of neuropathies. Both assess function of the peripheral nervous system and provide clinically useful information regarding the functional status of peripheral nerves. This information is not readily obtainable using biochemical, genetic or imaging techniques. I will discuss the role of these techniques in the diagnosis and management of neuropathies and some limitations of these techniques. These methods are routinely used in an EMG lab. These are most useful when used in conjunction with clinical examination to answer a well-defined clinical question. Reference values are required for interpretation of the data. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia.

PubMed

Horga, Alejandro; Pitceathly, Robert D S; Blake, Julian C; Woodward, Catherine E; Zapater, Pedro; Fratter, Carl; Mudanohwo, Ese E; Plant, Gordon T; Houlden, Henry; Sweeney, Mary G; Hanna, Michael G; Reilly, Mary M

2014-12-01

Progressive external ophthalmoplegia is a common clinical feature in mitochondrial disease caused by nuclear DNA defects and single, large-scale mitochondrial DNA deletions and is less frequently associated with point mutations of mitochondrial DNA. Peripheral neuropathy is also a frequent manifestation of mitochondrial disease, although its prevalence and characteristics varies considerably among the different syndromes and genetic aetiologies. Based on clinical observations, we systematically investigated whether the presence of peripheral neuropathy could predict the underlying genetic defect in patients with progressive external ophthalmoplegia. We analysed detailed demographic, clinical and neurophysiological data from 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia. Seventy-eight patients (67%) had a single mitochondrial DNA deletion, 12 (10%) had a point mutation of mitochondrial DNA and 26 (22%) had mutations in either POLG, C10orf2 or RRM2B, or had multiple mitochondrial DNA deletions in muscle without an identified nuclear gene defect. Seventy-seven patients had neurophysiological studies; of these, 16 patients (21%) had a large-fibre peripheral neuropathy. The prevalence of peripheral neuropathy was significantly lower in patients with a single mitochondrial DNA deletion (2%) as compared to those with a point mutation of mitochondrial DNA or with a nuclear DNA defect (44% and 52%, respectively; P<0.001). Univariate analyses revealed significant differences in the distribution of other clinical features between genotypes, including age at disease onset, gender, family history, progressive external ophthalmoplegia at clinical presentation, hearing loss, pigmentary retinopathy and extrapyramidal features. However, binomial logistic regression analysis identified peripheral neuropathy as the only independent predictor associated with a nuclear DNA defect (P=0.002; odds ratio 8.43, 95% confidence interval 2.24-31.76). Multinomial logistic regression analysis identified peripheral neuropathy, family history and hearing loss as significant predictors of the genotype, and the same three variables showed the highest performance in genotype classification in a decision tree analysis. Of these variables, peripheral neuropathy had the highest specificity (91%), negative predictive value (83%) and positive likelihood ratio (5.87) for the diagnosis of a nuclear DNA defect. These results indicate that peripheral neuropathy is a rare finding in patients with single mitochondrial DNA deletions but that it is highly predictive of an underlying nuclear DNA defect. This observation may facilitate the development of diagnostic algorithms. We suggest that nuclear gene testing may enable a more rapid diagnosis and avoid muscle biopsy in patients with progressive external ophthalmoplegia and peripheral neuropathy. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia

PubMed Central

Pitceathly, Robert D. S.; Blake, Julian C.; Woodward, Catherine E.; Zapater, Pedro; Fratter, Carl; Mudanohwo, Ese E.; Plant, Gordon T.; Houlden, Henry; Sweeney, Mary G.; Hanna, Michael G.; Reilly, Mary M.

2014-01-01

Progressive external ophthalmoplegia is a common clinical feature in mitochondrial disease caused by nuclear DNA defects and single, large-scale mitochondrial DNA deletions and is less frequently associated with point mutations of mitochondrial DNA. Peripheral neuropathy is also a frequent manifestation of mitochondrial disease, although its prevalence and characteristics varies considerably among the different syndromes and genetic aetiologies. Based on clinical observations, we systematically investigated whether the presence of peripheral neuropathy could predict the underlying genetic defect in patients with progressive external ophthalmoplegia. We analysed detailed demographic, clinical and neurophysiological data from 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia. Seventy-eight patients (67%) had a single mitochondrial DNA deletion, 12 (10%) had a point mutation of mitochondrial DNA and 26 (22%) had mutations in either POLG, C10orf2 or RRM2B, or had multiple mitochondrial DNA deletions in muscle without an identified nuclear gene defect. Seventy-seven patients had neurophysiological studies; of these, 16 patients (21%) had a large-fibre peripheral neuropathy. The prevalence of peripheral neuropathy was significantly lower in patients with a single mitochondrial DNA deletion (2%) as compared to those with a point mutation of mitochondrial DNA or with a nuclear DNA defect (44% and 52%, respectively; P < 0.001). Univariate analyses revealed significant differences in the distribution of other clinical features between genotypes, including age at disease onset, gender, family history, progressive external ophthalmoplegia at clinical presentation, hearing loss, pigmentary retinopathy and extrapyramidal features. However, binomial logistic regression analysis identified peripheral neuropathy as the only independent predictor associated with a nuclear DNA defect (P = 0.002; odds ratio 8.43, 95% confidence interval 2.24–31.76). Multinomial logistic regression analysis identified peripheral neuropathy, family history and hearing loss as significant predictors of the genotype, and the same three variables showed the highest performance in genotype classification in a decision tree analysis. Of these variables, peripheral neuropathy had the highest specificity (91%), negative predictive value (83%) and positive likelihood ratio (5.87) for the diagnosis of a nuclear DNA defect. These results indicate that peripheral neuropathy is a rare finding in patients with single mitochondrial DNA deletions but that it is highly predictive of an underlying nuclear DNA defect. This observation may facilitate the development of diagnostic algorithms. We suggest that nuclear gene testing may enable a more rapid diagnosis and avoid muscle biopsy in patients with progressive external ophthalmoplegia and peripheral neuropathy. PMID:25281868

Disabling Outcomes After Peripheral Vascular Catheter Insertion in a Newborn Patient: A Case of Medical Liability?

PubMed Central

Bolcato, Matteo; Russo, Marianna; Donadello, Damiano; Rodriguez, Daniele; Aprile, Anna

2017-01-01

Patient: Female, newborn Final Diagnosis: Loss of falange of the hand Symptoms: Manual disability • Pain Medication: Ampicilline Clinical Procedure: Insert vascular catheter Specialty: Forenscic Medicine Objective: Rare disease Background: The positioning of peripheral venous catheters (PVC) is an invasive procedure commonly performed in pediatrics hospital wards to obtain vascular access for the administration of fluids, medications and other intravenous (IV) therapies. Many studies exist about management of peripheral venous access in adults. On the contrary, scientific evidence on the management of this procedure in children and newborns, especially regarding the optimal duration of infusion and the possible related side effects, is still poor. To minimize the risk of phlebitis, the guidelines of the US Centers for Disease Control and Prevention suggest the replacement of the catheter every 72–96 hours in adult patients, while in pediatric patients the catheter can remain in place for the entire duration of the IV therapy, unless complications arise. Case Report: In the presented case, after the positioning of a PVC in a newborn, no clear signs/symptoms of phlebitis were registered before the sixth day and, despite the immediate removal of the catheter, the thrombotic process, secondary to phlebitis, was already occurring, causing serious and permanent disabling outcomes, susceptible to legal medical evaluation and financial compensation. Conclusions: The knowledge of this case is particularly interesting to clinicians working in the field of neonatal care and to clinical risk management services inside hospital structures, since similar cases may be the source of requests for extremely high financial compensations due to medical liability. PMID:29056746

Measures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data.

PubMed

Matsushita, Kunihiro; Ballew, Shoshana H; Coresh, Josef; Arima, Hisatomi; Ärnlöv, Johan; Cirillo, Massimo; Ebert, Natalie; Hiramoto, Jade S; Kimm, Heejin; Shlipak, Michael G; Visseren, Frank L J; Gansevoort, Ron T; Kovesdy, Csaba P; Shalev, Varda; Woodward, Mark; Kronenberg, Florian

2017-09-01

Some evidence suggests that chronic kidney disease is a risk factor for lower-extremity peripheral artery disease. We aimed to quantify the independent and joint associations of two measures of chronic kidney disease (estimated glomerular filtration rate [eGFR] and albuminuria) with the incidence of peripheral artery disease. In this collaborative meta-analysis of international cohorts included in the Chronic Kidney Disease Prognosis Consortium (baseline measurements obtained between 1972 and 2014) with baseline measurements of eGFR and albuminuria, at least 1000 participants (this criterion not applied to cohorts exclusively enrolling patients with chronic kidney disease), and at least 50 peripheral artery disease events, we analysed adult participants without peripheral artery disease at baseline at the individual patient level with Cox proportional hazards models to quantify associations of creatinine-based eGFR, urine albumin-to-creatinine ratio (ACR), and dipstick proteinuria with the incidence of peripheral artery disease (including hospitalisation with a diagnosis of peripheral artery disease, intermittent claudication, leg revascularisation, and leg amputation). We assessed discrimination improvement through c-statistics. We analysed 817 084 individuals without a history of peripheral artery disease at baseline from 21 cohorts. 18 261 cases of peripheral artery disease were recorded during follow-up across cohorts (median follow-up was 7·4 years [IQR 5·7-8·9], range 2·0-15·8 years across cohorts). Both chronic kidney disease measures were independently associated with the incidence of peripheral artery disease. Compared with an eGFR of 95 mL/min per 1·73 m 2 , adjusted hazard ratios (HRs) for incident study-specific peripheral artery disease was 1·22 (95% CI 1·14-1·30) at an eGFR of 45 mL/min per 1·73 m 2 and 2·06 (1·70-2·48) at an eGFR of 15 mL/min per 1·73 m 2 . Compared with an ACR of 5 mg/g, the adjusted HR for incident study-specific peripheral artery disease was 1·50 (1·41-1·59) at an ACR of 30 mg/g and 2·28 (2·12-2·44) at an ACR of 300 mg/g. The adjusted HR at an ACR of 300 mg/g versus 5 mg/g was 3·68 (95% CI 3·00-4·52) for leg amputation. eGFR and albuminuria contributed multiplicatively (eg, adjusted HR 5·76 [4·90-6·77] for incident peripheral artery disease and 10·61 [5·70-19·77] for amputation in eGFR <30 mL/min per 1·73 m 2 plus ACR ≥300 mg/g or dipstick proteinuria 2+ or higher vs eGFR ≥90 mL/min per 1·73 m 2 plus ACR <10 mg/g or dipstick proteinuria negative). Both eGFR and ACR significantly improved peripheral artery disease risk discrimination beyond traditional predictors, with a substantial improvement prediction of amputation with ACR (difference in c-statistic 0·058, 95% CI 0·045-0·070). Patterns were consistent across clinical subgroups. Even mild-to-moderate chronic kidney disease conferred increased risk of incident peripheral artery disease, with a strong association between albuminuria and amputation. Clinical attention should be paid to the development of peripheral artery disease symptoms and signs in people with any stage of chronic kidney disease. American Heart Association, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diabetic Foot Disease, Self-Care and Clinical Monitoring in Adults with Type 2 Diabetes: The Alberta's Caring for Diabetes (ABCD) Cohort Study.

PubMed

Al Sayah, Fatima; Soprovich, Allison; Qiu, Weiyu; Edwards, Alun L; Johnson, Jeffrey A

2015-10-01

To examine the prevalence and predictors of foot disease, self-care and clinical monitoring in adults with type 2 diabetes in Alberta, Canada. Baseline data from a prospective cohort of adults with type 2 diabetes were used. Assessment of foot disease included self-reported peripheral neuropathy, peripheral vasculopathy, foot or leg ulcer/infection or gangrene/amputation. Foot self-care was assessed using the Summary of Diabetes Self-Care Activities, and clinical monitoring using patients' reports of having feet checked for lesions or sensory loss. The mean age of respondents (N=2040) was 64 (SD 10.7) years; 45% were female, and 91% were Caucasian. Peripheral neuropathy was reported by 18% of the respondents, peripheral vasculopathy by 28%, ulcer/infection by 6% and gangrene/amputation by 1.4%. Only 14% of respondents performed foot self-care behaviours ≥6 days per week, and only 41% and 34% had their feet clinically checked for lesions or sensory loss, respectively. Predictors of foot disease included longer duration of diabetes, smoking, depressive symptoms, low self-efficacy and a history of cardiovascular diseases. Predictors of good self-care included older age, female sex, longer duration of diabetes and no report of hyperlipidemia. Predictors of clinical monitoring included female sex, current smoking, residing in urban areas, longer duration of diabetes, and histories of heart disease or hyperlipidemia. Peripheral neuropathy and vasculopathy were the most common reported foot problems in this population. Foot self-care is generally infrequent, and clinical monitoring is performed for less than half of these patients, with significant variations by patient demographics and clinical presentation. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Limb myokymia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albers, J.W.; Allen, A.A.; Bastron, J.A.

Thirty-eight patients with myokymic discharges localized to limb muscles on needle electromyography had various neurologic lesions, both acute and chronic. Of the 38 patients, 27 had had previous radiation therapy and the clinical diagnosis of radiation-induced plexopathy, myelopathy, or both. For the remaining 11 patients, the diagnoses included multiple sclerosis, inflammatory polyradiculoneuropathy, ischemic neuropathy, inflammatory myopathy, and chronic disorders of the spinal cord and peripheral nerves. The clinical presentations and results of local ischemia, peripheral nerve block, and percutaneous stimulation suggest that most limb myokymic discharges arise focally at the site of a chronic peripheral nerve lesion.

Benign Peripheral Nerve Sheath Tumor in a Wild Toco Toucan ( Ramphastos toco ).

PubMed

Carvalho, Marcelo P N; Fernandes, Natalia C C A; Nemer, Viviane C; Neto, Ramiro N Dias; Teixeira, Rodrigo H F; Miranda, Bruna S; Mamprim, Maria J; Catão-Dias, José L; Réssio, Rodrigo A

2016-09-01

Peripheral nerve sheath tumors are a heterogeneous group of neoplasms that comprise neurofibromas, schwannomas, neurilemmomas, and perineuromas. In animals, peripheral nerve sheath neoplasms are most commonly diagnosed in dogs and cattle, followed by horses, goats, and cats, but their occurrence is uncommon in birds. An adult, free-living, male toco (common) toucan ( Ramphastos toco ) was admitted to the zoo animal clinic with weight loss, dehydration, and presence of a soft nodule adhered to the medial portion of the left pectoral muscle. Clinical, cytologic, and computed tomography scan results were indicative of a neoplasm. The toucan died during surgical resection of the mass. Necropsy, histopathologic, and immunohistochemical findings confirmed the diagnosis of benign peripheral nerve sheath tumor. To our knowledge, benign peripheral nerve sheath tumor has not previously been reported in a toucan or any other species in the order Piciformes.

Optic ataxia and the function of the dorsal stream: contributions to perception and action.

PubMed

Pisella, Laure; Sergio, Lauren; Blangero, Annabelle; Torchin, Héloïse; Vighetto, Alain; Rossetti, Yves

2009-12-01

Optic ataxia (OA) is one of the symptoms pertaining to Bálint's Syndrome. It has been described clinically for nearly 80 years before it became a cornerstone of the most popular dual stream theory of the visual brain. Over the last 10 years a regain of interest for this neurological condition lead to a number of precise analyses of the deficits found in optic ataxia, giving rise to a renewed outline of its very definition and hence of the function(s) of the occipito-parietal (dorsal) stream. In absence of concomitant clinical symptoms, we review evidence that misreaching errors in central vision result from the "hand effect": an erroneous dynamic spatial processing of proprioceptive information from the hand. When visual feedback of the hand is provided (closed-loop condition), pure optic ataxia is restricted to peripheral vision. This central versus peripheral vision distinction is repeatedly used to argue that action and perception are not unique and dissociated systems. New assessments of optic ataxia patients are provided, confirming on one hand that their visuomotor deficit is specific to peripheral vision (i.e. when the gaze and the hand goals are dissociated), on the other hand that they disclose perceptual deficits in peripheral vision. These results are coherent with the recent demonstration that optic ataxia patients exhibit a general contralesional deficit for dynamic visuo-spatial processing, affecting both hand and eye movements [Gaveau, V., Pélisson, D., Blangero, A., Urquizar, C., Prablanc, C.,Vighetto, A., et al. (2008). A common parietal module for saccade and reach: Eye-hand coordination and saccadic control in optic ataxia. Neuropsychologia, 46, 475-486]. Such module(s) within the dorsal stream could be used for both action and perception in the periphery. It is concluded that optic ataxia cannot be considered as a unitary and specific visuo-manual deficit, and that the modular organisation of the dorsal stream allows for numerous dorsal-ventral interactions for perception and action.

Peripheral visual performance enhancement by neurofeedback training.

PubMed

Nan, Wenya; Wan, Feng; Lou, Chin Ian; Vai, Mang I; Rosa, Agostinho

2013-12-01

Peripheral visual performance is an important ability for everyone, and a positive inter-individual correlation is found between the peripheral visual performance and the alpha amplitude during the performance test. This study investigated the effect of alpha neurofeedback training on the peripheral visual performance. A neurofeedback group of 13 subjects finished 20 sessions of alpha enhancement feedback within 20 days. The peripheral visual performance was assessed by a new dynamic peripheral visual test on the first and last training day. The results revealed that the neurofeedback group showed significant enhancement of the peripheral visual performance as well as the relative alpha amplitude during the peripheral visual test. It was not the case in the non-neurofeedback control group, which performed the tests within the same time frame as the neurofeedback group but without any training sessions. These findings suggest that alpha neurofeedback training was effective in improving peripheral visual performance. To the best of our knowledge, this is the first study to show evidence for performance improvement in peripheral vision via alpha neurofeedback training.

A Clinical and Histological Analysis of Mesenchymal Stem Cells in Amputation

ClinicalTrials.gov

2017-08-08

Ischemia; Peripheral Arterial Disease; Peripheral Vascular Disease; Vascular Disease; Arterial Occlusive Disease; Arteriosclerosis; Atherosclerosis; Cardiovascular Disease; Pathologic Processes; Orthopedic Procedures; Amputation

[Clinical Applications of Peripheral Markers of Response in Antidepressant Treatment: Neurotrophins and Cytokines].

PubMed

Bermúdez, Constanza Mendoza

2012-03-01

Explanatory theories of depression have advanced in recent decades from the monoaminergic hypothesis to neurogenesis alterations to the neurohormonal hypothesis that includes the dysfunction of the inflammatory response. Currently there is a growing interest in the development of biomarkers that can contribute to diagnosis and proper treatment. To describe the role of neurotrophins such as brain-derived neurotrophic factor (BDNF) and cytokines in the pathophysiology of depressive disorder in addition to reviewing and analyzing evidence about their clinical application as biomarkers of antidepressant therapy. Relevant data research in several databases. In recent years evidence of alterations in neurogenesis mediated by the expression of BDNF in the hippocampus in the pathophysiology of depression has increased and there is ample evidence that BDNF is a marker of the diagnosis of depressive disorder and also of treatment effectiveness. There is little information about other neurotrophins. There has also been increased interest in relation to depression as an "inflammatory disease" and the link with cytokines in its pathogenesis. Evidence has been found for the usefulness of some cytokines especially IL-1 (interleukin 1), IL-6 (interleukin 6), and TNF (tumor necrosis factor) as biomarkers of antidepressant drug response in humans. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Revisiting the evidence for neuropathy caused by pyridoxine deficiency and excess.

PubMed

Ghavanini, Amer A; Kimpinski, Kurt

2014-09-01

Pyridoxine deficiency and excess have been implicated as a cause for peripheral neuropathy. As a result, unrelated neuropathies are often treated with pyridoxine based on questionable evidence. However, neurological practitioners frequently discourage patients from taking pyridoxine in excess of 50 mg/d given concerns around the development of a toxic sensory neuronopathy. There is no systematic review to support either of the 2 practices. To address this gap in knowledge, we reviewed the available literature on neuropathy attributed to pyridoxine deficiency and excess. Based on the current limited data, it can be concluded that very low doses of daily pyridoxine are required to prevent peripheral neuropathy. There is inadequate evidence to support routine pyridoxine supplementation in patients with disorders of peripheral nervous system. Supplementation with pyridoxine at doses greater than 50 mg/d for extended duration may be harmful and should be discouraged.

Fate of combat nerve injury.

PubMed

Beltran, Michael J; Burns, Travis C; Eckel, Tobin T; Potter, Benjamin K; Wenke, Joseph C; Hsu, Joseph R

2012-11-01

Assess a cohort of combat-related type III open tibia fractures with peripheral nerve injury to determine the injury mechanism and likelihood for recovery or improvement in nerve function. Retrospective study. Three military medical centers. Out of a study cohort of 213 type III open tibia fractures, 32 fractures (in 32 patients) with a total of 43 peripheral nerve injuries (peroneal or tibial) distal to the popliteal fossa met inclusion criteria and were available for follow-up at an average of 20 months (range, 2-48 months). Clinical assessment of motor and sensory nerve improvement. There was a 22% incidence of peripheral nerve injury in the study cohort. At an average follow-up of 20 months (range, 2-48 months), 89% of injured motor nerves were functional, whereas the injured sensory nerves had function in 93%. Fifty percent and 27% of motor and sensory injuries demonstrated improvement, respectively (P = 0.043). With the numbers available, there was no difference in motor or sensory improvement based on mechanism of injury, fracture severity or location, soft tissue injury, or specific nerve injured. In the subset of patients with an initially impaired sensory examination, full improvement was related to fracture location (P = 0.0164). Type III open tibia fractures sustained in combat are associated with a 22% incidence of peripheral nerve injury, and the majority are due to multiple projectile penetrating injury. Despite the severe nature of these injuries, the vast majority of patients had a functional nerve status by an average of 2-year follow-up. Based on these findings, discussions regarding limb salvage and amputation should not be overly influenced by the patient's peripheral nerve status. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Reduced Activated T Lymphocytes (CD4+CD25+) and Plasma Levels of Cytokines in Parkinson's Disease.

PubMed

Rocha, Natalia Pessoa; Assis, Frankcinéia; Scalzo, Paula Luciana; Vieira, Érica Leandro Marciano; Barbosa, Izabela Guimarães; de Souza, Mariana Soares; Christo, Paulo Pereira; Reis, Helton José; Teixeira, Antonio Lucio

2018-02-01

Parkinson's disease (PD) is the second most common neurodegenerative disease. The cause of neurodegeneration in PD is not completely understood, and evidence has shown that inflammatory/immune changes may be involved in PD pathophysiology. Herein, we aimed to determine the profile of the peripheral immune system in patients with PD in comparison with controls. Forty patients with PD and 25 age- and gender-matched controls were enrolled in this study. From these, 23 PD patients and 21 controls were included in the immunophenotyping analyses. Peripheral blood was drawn on the same day of the clinical assessment and submitted to plasma separation for enzyme-linked immunosorbent assay or cytometric bead array. Immunophenotyping analyses of the peripheral blood were performed by flow cytometry. We found that patients with PD presented peripheral immune changes evidenced by decreased percentage of T lymphocytes (CD3+ cells), especially activated T lymphocytes (CD4+CD25+ cells), when compared with controls. In line with these results, we also found decreased plasma levels of the cytokines IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17A in the PD group. In vitro experiments demonstrated that the production of cytokines by peripheral blood mononuclear cells harvested from healthy young donors was reduced after exposure to the anti-parkinsonian drugs levodopa and pramipexole. Our data corroborate the hypothesis that immunological mechanisms are involved in PD. It is not clear whether the differences that we have found are due to adaptive mechanisms or to changes associated with PD, including pharmacological treatment, or even directly related to the disease pathophysiology. Future studies are needed in this regard.

Hidden dangers revealed by misdiagnosed diabetic neuropathy: A comparison of simple clinical tests for the screening of vibration perception threshold at primary care level.

PubMed

Azzopardi, Kurt; Gatt, Alfred; Chockalingam, Nachiappan; Formosa, Cynthia

2018-04-01

Diabetic peripheral neuropathy is an important complication and contributes to the morbidity of diabetes mellitus. Evidence indicates early detection of diabetic peripheral neuropathy results in fewer foot ulcers and amputations. The aim of this study was to compare different screening modalities in the detection of diabetic peripheral neuropathy in a primary care setting. A prospective non-experimental comparative multi-centre cross sectional study was conducted in various Primary Health Centres. One hundred participants living with Type 2 diabetes for at least 10 years were recruited using a convenience sampling method. The Vibratip, 128Hz tuning fork and neurothesiometer were compared in the detection of vibration perception. This study showed different results of diabetic peripheral neuropathy screening tests, even in the same group of participants. This study has shown that the percentage of participants who did not perceive vibrations was highest when using the VibraTip (28.5%). This was followed by the neurothesiometer (21%) and the 128Hz tuning fork (12%) (p<0.001). Correct diagnosis and treatment of neuropathy in patients with diabetes is crucial. This study demonstrates that some instruments are more sensitive to vibration perception than others. We recommend that different modalities should be used in patients with diabetes and when results do not concur, further neurological evaluation should be performed. This would significantly reduce the proportion of patients with diabetes who would be falsely identified as having no peripheral neuropathy and subsequently denied the benefit of beneficial and effective secondary risk factor control. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Nervous System Sensitization as a Predictor of Outcome in the Treatment of Peripheral Musculoskeletal Conditions: A Systematic Review.

PubMed

O'Leary, Helen; Smart, Keith M; Moloney, Niamh A; Doody, Catherine M

2017-02-01

Research suggests that peripheral and central nervous system sensitization can contribute to the overall pain experience in peripheral musculoskeletal (MSK) conditions. It is unclear, however, whether sensitization of the nervous system results in poorer outcomes following the treatment. This systematic review investigated whether nervous system sensitization in peripheral MSK conditions predicts poorer clinical outcomes in response to a surgical or conservative intervention. Four electronic databases were searched to identify the relevant studies. Eligible studies had a prospective design, with a follow-up assessing the outcome in terms of pain or disability. Studies that used baseline indices of nervous system sensitization were included, such as quantitative sensory testing (QST) or questionnaires that measured centrally mediated symptoms. Thirteen studies met the inclusion criteria, of which six were at a high risk of bias. The peripheral MSK conditions investigated were knee and hip osteoarthritis, shoulder pain, and elbow tendinopathy. QST parameters indicative of sensitization (lower electrical pain thresholds, cold hyperalgesia, enhanced temporal summation, lower punctate sharpness thresholds) were associated with negative outcome (more pain or disability) in 5 small exploratory studies. Larger studies that accounted for multiple confounders in design and analysis did not support a predictive relationship between QST parameters and outcome. Two studies used self-report measures to capture comorbid centrally mediated symptoms, and found higher questionnaire scores were independently predictive of more persistent pain following a total joint arthroplasty. This systematic review found insufficient evidence to support an independent predictive relationship between QST measures of nervous system sensitization and treatment outcome. Self-report measures demonstrated better predictive ability. Further high-quality prognostic research is warranted. © 2016 World Institute of Pain.

Otoneurological symptoms in Brazilian fishermen exposed over a long period to carbon monoxide and noise

PubMed Central

Zeigelboim, Bianca Simone; Santos da Carvalho, Hugo Amilton; de Oliveira Gonçalves, Claudia Giglio; Albizu, Evelyn Joice; Marques, Jair Mendes; Fuck, Bruna Carla; Cardoso, Rafaella

2015-01-01

Fishing, one of the oldest productive activities, is an important sector of the Brazilian economy as well as the world economy. To evaluate the vestibular behavior in population of fishermen. It was realized as a retrospective and cross-sectional study. Thirty fishermen [mean age 49.5 (±8.5) years] whose age ranged from 33 years to 67 years were submitted to anamnesis, otorhinolaryngological evaluation, and vestibular examination through the electronystagmography (ENG). The most evident otoneurological symptoms were: Tinnitus (66.7%), dizziness (63.3%), and hearing loss (53.3%). The most evident clinical symptoms were: Fatigue (36.7%), anxiety (23.3%), and depression (16.7%). There were alterations in the vestibular examination of 13 (43.3%) fishermen in the caloric test. There was a prevalence of alteration in the peripheral vestibular system and there was a major frequency of the peripheral vestibular irritative syndrome (30.0%). Conclusion: The otoneurological complaints were frequent in the population studied that verifies the importance of allowing labyrinth examinations and the need for adopting preventive measures related to noise exposure to carbon monoxide (CO), since they can cause and/enhance various manifestations of labyrinthine vestibular impairment that can affect the quality of life of these workers. PMID:26356372

Otoneurologic Findings in a Fishermen Population of the State of Santa Catarina: Preliminary Study

PubMed Central

Zeigelboim, Bianca Simone; da Silva, Thanara Pruner; Carvalho, Hugo; de Brito Malucelli, Diego Augusto; de Oliveira Gonçalves, Claudia Giglio; Albizu, Evelyn Joyce; Liberalesso, Paulo Breno Noronha; de Lacerda, Adriana Bender Moreira; Barilari, Gerusa Lopes

2013-01-01

Introduction Fishing, one of the oldest productive activities, is an important sector of the national and world economy. Aim To evaluate the vestibular behavior in a population of fishermen. Methods In a retrospective and cross-sectional study, 13 fishermen (mean 45.0), between 33 and 62 years of age, were submitted to anamnesis, otorhinolaryngological evaluation, and vestibular exam through the vector electronystagmography. Results The most evident otoneurologic symptoms were hearing loss (76.9%), tinnitus (61.7%), dizziness (46.1%), and headache (46.1%). The most evident clinical symptoms were fatigue (46.1%), depression (23.0%), anxiety (15.3%), insomnia (7.7%), and agitation during sleep (7.7%). There were alterations in the vestibular exam in 5 fishermen (38.5%) discovered in the caloric test. There was a prevalence of alteration in the peripheral vestibular system. There was a major frequency of the peripheral vestibular irritative syndrome. Conclusion The otoneurologic complaints were frequent in the population studied to verify the importance of allowing labyrinth exams and the need for adopting preventive measures relating to noise exposure as well as carbon monoxide exposure, because they can cause and/or enhance various manifestations of labyrinthine vestibular impairment that can affect the quality of life of these workers. PMID:25992055

Clinical classification in low back pain: best-evidence diagnostic rules based on systematic reviews.

PubMed

Petersen, Tom; Laslett, Mark; Juhl, Carsten

2017-05-12

Clinical examination findings are used in primary care to give an initial diagnosis to patients with low back pain and related leg symptoms. The purpose of this study was to develop best evidence Clinical Diagnostic Rules (CDR] for the identification of the most common patho-anatomical disorders in the lumbar spine; i.e. intervertebral discs, sacroiliac joints, facet joints, bone, muscles, nerve roots, muscles, peripheral nerve tissue, and central nervous system sensitization. A sensitive electronic search strategy using MEDLINE, EMBASE and CINAHL databases was combined with hand searching and citation tracking to identify eligible studies. Criteria for inclusion were: persons with low back pain with or without related leg symptoms, history or physical examination findings suitable for use in primary care, comparison with acceptable reference standards, and statistical reporting permitting calculation of diagnostic value. Quality assessments were made independently by two reviewers using the Quality Assessment of Diagnostic Accuracy Studies tool. Clinical examination findings that were investigated by at least two studies were included and results that met our predefined threshold of positive likelihood ratio ≥ 2 or negative likelihood ratio ≤ 0.5 were considered for the CDR. Sixty-four studies satisfied our eligible criteria. We were able to construct promising CDRs for symptomatic intervertebral disc, sacroiliac joint, spondylolisthesis, disc herniation with nerve root involvement, and spinal stenosis. Single clinical test appear not to be as useful as clusters of tests that are more closely in line with clinical decision making. This is the first comprehensive systematic review of diagnostic accuracy studies that evaluate clinical examination findings for their ability to identify the most common patho-anatomical disorders in the lumbar spine. In some diagnostic categories we have sufficient evidence to recommend a CDR. In others, we have only preliminary evidence that needs testing in future studies. Most findings were tested in secondary or tertiary care. Thus, the accuracy of the findings in a primary care setting has yet to be confirmed.

Diagnosis and management of Lyme neuroborreliosis.

PubMed

Halperin, John J

2018-01-01

The nervous system is involved in 10-15% of patients infected with B. burgdorferi, B. afzelii and B. garinii. This review will address widespread misconceptions about the clinical phenomenology, diagnostic approach and response to treatment of neuroborreliosis. Areas covered: Improvements in diagnostic testing have allowed better definition of the clinical spectrum of neuroborreliosis, with lymphocytic meningitis and uni- or multifocal inflammation of peripheral/cranial nerves predominating. Despite widespread concern that post-treatment cognitive/behavioral symptoms might be attributable to persisting infection or aberrant inflammation within the central nervous system a large body of evidence indicates this is extremely improbable. Importantly, recent studies show most neuroborreliosis can be treated with fairly brief courses of oral antibiotics. All high-level evidence confirms that prolonged courses of antibiotics carry harm with no commensurate benefit. Expert commentary: Lyme disease in the US, and corresponding disorders in Europe, are well defined neuro-infectious diseases that are highly responsive to antibiotic therapy. Although the nervous system is slow to recover after insults (e.g. persistent facial weakness after appropriately treated facial nerve palsy) there is no evidence that prolonged post-treatment neurocognitive symptoms are related to nervous system infection - either as a triggering event or as a cause of ongoing symptoms.

Emerging nanotechnology approaches in tissue engineering for peripheral nerve regeneration.

PubMed

Cunha, Carla; Panseri, Silvia; Antonini, Stefania

2011-02-01

Effective nerve regeneration and functional recovery subsequent to peripheral nerve injury is still a clinical challenge. Autologous nerve graft transplantation is a feasible treatment in several clinical cases, but it is limited by donor site morbidity and insufficient donor tissue, impairing complete functional recovery. Tissue engineering has introduced innovative approaches to promote and guide peripheral nerve regeneration by using biomimetic conduits creating favorable microenvironments for nervous ingrowth, but despite the development of a plethora of nerve prostheses, few approaches have as yet entered the clinic. Promising strategies using nanotechnology have recently been proposed, such as the use of scaffolds with functionalized cell-binding domains, the use of guidance channels with cell-scale internally oriented fibers, and the possibility of sustained release of neurotrophic factors. This review addresses the fabrication, advantages, drawbacks, and results achieved by the most recent nanotechnology approaches in view of future solutions for peripheral nerve repair. Peripheral nerve repair strategies are very limited despite numerous advances on the field of neurosciences and regenerative medicine. This review discusses nanotechnology based strategies including scaffolds with functionalized cell binding domains, the use of guidance channels, and the potential use of sustained release neurotropic factors. Copyright © 2011 Elsevier Inc. All rights reserved.

In vivo targeted peripheral nerve imaging with a nerve-specific nanoscale magnetic resonance probe.

PubMed

Zheng, Linfeng; Li, Kangan; Han, Yuedong; Wei, Wei; Zheng, Sujuan; Zhang, Guixiang

2014-11-01

Neuroimaging plays a pivotal role in clinical practice. Currently, computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography, and positron emission tomography (PET) are applied in the clinical setting as neuroimaging modalities. There is no optimal imaging modality for clinical peripheral nerve imaging even though fluorescence/bioluminescence imaging has been used for preclinical studies on the nervous system. Some studies have shown that molecular and cellular MRI (MCMRI) can be used to visualize and image the cellular and molecular level of the nervous system. Other studies revealed that there are different pathological/molecular changes in the proximal and distal sites after peripheral nerve injury (PNI). Therefore, we hypothesized that in vivo peripheral nerve targets can be imaged using MCMRI with specific MRI probes. Specific probes should have higher penetrability for the blood-nerve barrier (BNB) in vivo. Here, a functional nanometre MRI probe that is based on nerve-specific proteins as targets, specifically, using a molecular antibody (mAb) fragment conjugated to iron nanoparticles as an MRI probe, was constructed for further study. The MRI probe allows for imaging the peripheral nerve targets in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

Flow cytometric minimal residual disease assessment of peripheral blood in acute lymphoblastic leukaemia patients has potential for early detection of relapsed extramedullary disease.

PubMed

Keegan, Alissa; Charest, Karry; Schmidt, Ryan; Briggs, Debra; Deangelo, Daniel J; Li, Betty; Morgan, Elizabeth A; Pozdnyakova, Olga

2018-03-27

To evaluate peripheral blood (PB) for minimal residual disease (MRD) assessment in adults with acute lymphoblastic leukaemia (ALL). We analysed 76 matched bone marrow (BM) aspirate and PB specimens independently for the presence of ALL MRD by six-colour flow cytometry (FC). The overall rate of BM MRD-positivity was 24% (18/76) and PB was also MRD-positive in 22% (4/18) of BM-positive cases. We identified two cases with evidence of leukaemic cells in PB at the time of the extramedullary relapse that were interpreted as MRD-negative in BM. The use of PB MRD as a non-invasive method for monitoring of systemic relapse may have added clinical and diagnostic value in patients with high risk of extramedullary disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Insights into Neuroinflammation in Parkinson's Disease: From Biomarkers to Anti-Inflammatory Based Therapies.

PubMed

Rocha, Natália Pessoa; de Miranda, Aline Silva; Teixeira, Antônio Lúcio

2015-01-01

Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide, being characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Among several putative factors that may contribute to PD pathogenesis, inflammatory mechanisms may play a pivotal role. The involvement of microglial activation as well as of brain and peripheral immune mediators in PD pathophysiology has been reported by clinical and experimental studies. These inflammatory biomarkers evaluated by imaging techniques and/or by biological sample analysis have become valuable tools for PD diagnosis and prognosis. Regardless of the significant increase in the number of people suffering from PD, there are still no established disease-modifying or neuroprotective therapies for it. There is growing evidence of protective effect of anti-inflammatory drugs on PD development. Herein, we reviewed the current literature regarding the central nervous system and peripheral immune biomarkers in PD and advances in diagnostic and prognostic tools as well as the neuroprotective effects of anti-inflammatory therapies.

Botulinum Toxin for the Treatment of Neuropathic Pain

PubMed Central

Park, JungHyun; Park, Hue Jung

2017-01-01

Botulinum toxin (BoNT) has been used as a treatment for excessive muscle stiffness, spasticity, and dystonia. BoNT for approximately 40 years, and has recently been used to treat various types of neuropathic pain. The mechanism by which BoNT acts on neuropathic pain involves inhibiting the release of inflammatory mediators and peripheral neurotransmitters from sensory nerves. Recent journals have demonstrated that BoNT is effective for neuropathic pain, such as postherpetic neuralgia, trigeminal neuralgia, and peripheral neuralgia. The purpose of this review is to summarize the experimental and clinical evidence of the mechanism by which BoNT acts on various types of neuropathic pain and describe why BoNT can be applied as treatment. The PubMed database was searched from 1988 to May 2017. Recent studies have demonstrated that BoNT injections are effective treatments for post-herpetic neuralgia, diabetic neuropathy, trigeminal neuralgia, and intractable neuropathic pain, such as poststroke pain and spinal cord injury. PMID:28837075

Osseoperception: An Implant Mediated Sensory Motor Control- A Review

PubMed Central

Karani, Jyoti T.; Khanna, Anshul; Badwaik, Praveen; Pai, Ashutosh

2015-01-01

Osseointegration of dental implants has been researched extensively, covering various aspects such as bone apposition, biomechanics and microbiology etc however, physiologic integration of implants and the associated prosthesis in the body has received very little attention. This integration is due to the development of a special sensory ability, which is able to restore peripheral sensory feedback mechanism. The underlying mechanism of this so-called ‘osseoperception’ phenomenon remains a matter of debate. The following article reveals the histological, neurophysiologic and psychophysical aspects of osseoperception. A comprehensive research to provide scientific evidence of osseoperception was carried out using various online resources such as Pubmed, Google scholar etc to retrieve studies published between 1985 to 2014 using the following keywords: “osseoperception”, “mechanoreceptors”, “tactile sensibility”. Published data suggests that a peripheral feedback pathway can be restored with osseointegrated implants. This implant-mediated sensory-motor control may have important clinical implications in the normal functioning of the implant supported prosthesis. PMID:26501033

Cystic adventitial degeneration: ectopic ganglia from adjacent joint capsules.

PubMed

Ortmann, J; Widmer, M K; Gretener, S; Do, D D; Willenberg, T; Daliri, A; Baumgartner, I

2009-11-01

Cystic adventitial degeneration is a rare non-atherosclerotic cause of peripheral arterial occlusive disease, mainly seen in young men without other evidence of vascular disease. Diagnosis will be established by clinical findings and by ultrasound or angiography and can be treated by excision or enucleation of the affected arterial segment or by percutaneous ultrasound-guided aspiration. However, the etiology of adventitial cysts remains unknown. We report a case of cystic adventitial degeneration showing a connection between the joint capsule and the adventitial cyst, supporting the theory that cystic adventitial degeneration may represent ectopic ganglia from adjacent joint capsules.

[Immunopathology of ulcerative colitis and granulomatous colitis (author's transl)].

PubMed

Bläker, F

1975-08-01

There is no convincing evidence as yet for a key role of immunological processes in the pathogenesis of unspecific colitis. However clinical findings as well as immunological data do support the hypothesis that immune reactions are involved primarily or secondarily in the pathogenesis and the clinical course of ulcerative colitis and granulomatous colitis. In such patients a specific adaptation of humoral and cell-bound immune reactions against antigenic material from the colon and other tissues has been found in peripheral blood, lymphatic tissue and bowel wall. In this context it seems to be especially noteworthy, that lymphocytes taken from patients with colitis lead to disintegration of colon epithelial cells in vitro. This cytotoxic effect of the lymphocytes is lost after colectomy or remission of the disease. Ulcerative and granulomatous colitis do have many clinical and immunological peculiarities in common. This makes one think, that possibly the same noxious factors induce differential local reactions because of different hereditary disposition.

[Etiopathogenetic and clinical notes on the syndrome of the micropolycystic hyperandrogenic ovary and matrimonial sterility].

PubMed

Giarola, A; Rolandi, L

1977-01-14

The nosological, clinical, aetiopathogenetic and therapeutic aspects of hyperandrogenic micropolycystic ovary are examined with particular reference to matrimonial sterility. There is not doubt about the existence of a syndrome substantially characterized, clinically, by menstrual trouble, inability to procreate, more or less evident signs of hyperandrogenism and a tendency to obesity and, morphologically, by ovarian micropolycystic alterations of typical pathognomonic aspect: the marked production of androgens on the part of the female gonad possibly accompanied by peripheral alterations interfering with their metabolism. The syndrome is not too frequent and, in personal experience, occurs in less than 1% of the series. The main therapeutic approach remains cuneiform resection of the ovary. Still in personal experience, 21.2% of cases treated led to pregnancy but not more than eight-ten months after operation. The effect would therefore appear to be transitory and the operation is decisively rejected where unmarried women are involved.

Genetic predisposition to peripheral nerve neoplasia: Diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes

PubMed Central

Rodriguez, Fausto J.; Stratakis, Constantine A.; Evans, D Gareth

2013-01-01

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately a third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney Complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia. PMID:22210082

Genetic predisposition to peripheral nerve neoplasia: diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes.

PubMed

Rodriguez, Fausto J; Stratakis, Constantine A; Evans, D Gareth

2012-03-01

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system, and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately one-third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET, respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia.

Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies.

PubMed

Fernandes, Brisa S; Molendijk, Marc L; Köhler, Cristiano A; Soares, Jair C; Leite, Cláudio Manuel G S; Machado-Vieira, Rodrigo; Ribeiro, Thamara L; Silva, Jéssica C; Sales, Paulo M G; Quevedo, João; Oertel-Knöchel, Viola; Vieta, Eduard; González-Pinto, Ana; Berk, Michael; Carvalho, André F

2015-11-30

The neurotrophic hypothesis postulates that mood disorders such as bipolar disorder (BD) are associated with a lower expression of brain-derived neurotrophic factor (BDNF). However, its role in peripheral blood as a biomarker of disease activity and of stage for BD, transcending pathophysiology, is still disputed. In the last few years an increasing number of clinical studies assessing BDNF in serum and plasma have been published. Therefore, it is now possible to analyse the association between BDNF levels and the severity of affective symptoms in BD as well as the effects of acute drug treatment of mood episodes on BDNF levels. We conducted a systematic review and meta-analysis of all studies on serum and plasma BDNF levels in bipolar disorder. Through a series of meta-analyses including a total of 52 studies with 6,481 participants, we show that, compared to healthy controls, peripheral BDNF levels are reduced to the same extent in manic (Hedges' g = -0.57, P = 0.010) and depressive (Hedges' g = -0.93, P = 0.001) episodes, while BDNF levels are not significantly altered in euthymia. In meta-regression analyses, BDNF levels additionally negatively correlate with the severity of both manic and depressive symptoms. We found no evidence for a significant impact of illness duration on BDNF levels. In addition, in plasma, but not serum, peripheral BDNF levels increase after the successful treatment of an acute mania episode, but not of a depressive one. In summary, our data suggest that peripheral BDNF levels, more clearly in plasma than in serum, is a potential biomarker of disease activity in BD, but not a biomarker of stage. We suggest that peripheral BDNF may, in future, be used as a part of a blood protein composite measure to assess disease activity in BD.

RNA-Stabilized Whole Blood Samples but Not Peripheral Blood Mononuclear Cells Can Be Stored for Prolonged Time Periods Prior to Transcriptome Analysis

PubMed Central

Debey-Pascher, Svenja; Hofmann, Andrea; Kreusch, Fatima; Schuler, Gerold; Schuler-Thurner, Beatrice; Schultze, Joachim L.; Staratschek-Jox, Andrea

2011-01-01

Microarray-based transcriptome analysis of peripheral blood as surrogate tissue has become an important approach in clinical implementations. However, application of gene expression profiling in routine clinical settings requires careful consideration of the influence of sample handling and RNA isolation methods on gene expression profile outcome. We evaluated the effect of different sample preservation strategies (eg, cryopreservation of peripheral blood mononuclear cells or freezing of PAXgene-stabilized whole blood samples) on gene expression profiles. Expression profiles obtained from cryopreserved peripheral blood mononuclear cells differed substantially from those of their nonfrozen counterpart samples. Furthermore, expression profiles in cryopreserved peripheral blood mononuclear cell samples were found to undergo significant alterations with increasing storage period, whereas long-term freezing of PAXgene RNA stabilized whole blood samples did not significantly affect stability of gene expression profiles. This report describes important technical aspects contributing toward the establishment of robust and reliable guidance for gene expression studies using peripheral blood and provides a promising strategy for reliable implementation in routine handling for diagnostic purposes. PMID:21704280

Marvels, mysteries, and misconceptions of vascular compensation to peripheral artery occlusion.

PubMed

Ziegler, Matthew A; Distasi, Matthew R; Bills, Randall G; Miller, Steven J; Alloosh, Mouhamad; Murphy, Michael P; Akingba, A George; Sturek, Michael; Dalsing, Michael C; Unthank, Joseph L

2010-01-01

Peripheral arterial disease is a major health problem and there is a significant need to develop therapies to prevent its progression to claudication and critical limb ischemia. Promising results in rodent models of arterial occlusion have generally failed to predict clinical success and led to questions of their relevance. While sub-optimal models may have contributed to the lack of progress, we suggest that advancement has also been hindered by misconceptions of the human capacity for compensation and the specific vessels which are of primary importance. We present and summarize new and existing data from humans, Ossabaw miniature pigs, and rodents which provide compelling evidence that natural compensation to occlusion of a major artery (i) may completely restore perfusion, (ii) occurs in specific pre-existing small arteries, rather than the distal vasculature, via mechanisms involving flow-mediated dilation and remodeling (iii) is impaired by cardiovascular risk factors which suppress the flow-mediated mechanisms and (iv) can be restored by reversal of endothelial dysfunction. We propose that restoration of the capacity for flow-mediated dilation and remodeling in small arteries represents a largely unexplored potential therapeutic opportunity to enhance compensation for major arterial occlusion and prevent the progression to critical limb ischemia in the peripheral circulation.

Marvels, Mysteries, and Misconceptions of Vascular Compensation to Peripheral Artery Occlusion

PubMed Central

ZIEGLER, MATTHEW A.; DISTASI, MATTHEW R.; BILLS, RANDALL G.; MILLER, STEVEN J.; ALLOOSH, MOUHAMAD; MURPHY, MICHAEL P.; AKINGBA, A. GEORGE; STUREK, MICHAEL; DALSING, MICHAEL C.; UNTHANK, JOSEPH L.

2010-01-01

Peripheral arterial disease is a major health problem and there is a significant need to develop therapies to prevent its progression to claudication and critical limb ischemia. Promising results in rodent models of arterial occlusion have generally failed to predict clinical success and led to questions of their relevance. While sub-optimal models may have contributed to the lack of progress, we suggest that advancement has also been hindered by misconceptions of the human capacity for compensation and the specific vessels which are of primary importance. We present and summarize new and existing data from humans, Ossabaw miniature pigs, and rodents which provide compelling evidence that natural compensation to occlusion of a major artery (i) may completely restore perfusion, (ii) occurs in specific pre-existing small arteries, rather than the distal vasculature, via mechanisms involving flow-mediated dilation and remodeling (iii) is impaired by cardiovascular risk factors which suppress the flow-mediated mechanisms and (iv) can be restored by reversal of endothelial dysfunction. We propose that restoration of the capacity for flow-mediated dilation and remodeling in small arteries represents a largely unexplored potential therapeutic opportunity to enhance compensation for major arterial occlusion and prevent the progression to critical limb ischemia in the peripheral circulation. PMID:20141596

Antithrombotic therapy in peripheral artery disease: A review of the EUCLID trial results and current ongoing trials.

PubMed

Ward, Rachael; Long, Chandler; Patel, Manesh R; Jones, William S

2018-01-01

In addition to risk-factor modification, antithrombotic therapy is the hallmark of management to reduce cardiovascular ischemic events in patients with peripheral artery disease (PAD). Currently, the guidelines recommend long-term antiplatelet therapy with aspirin or clopidogrel in this patient population to reduce myocardial infarction, stroke, and vascular death. Past outcomes studies have shown some benefit of ticagrelor, another antiplatelet agent, as compared with clopidogrel in patients with coronary disease and concomitant PAD. However, most recently, the Examining Use of Ticagrelor in Peripheral Artery Disease (EUCLID) trial has shown no additional benefit of ticagrelor over clopidogrel. In this trial, a minority of patients had concomitant coronary artery disease, making it unique to previous studies. The EUCLID trial's evidence of neutrality between clopidogrel and ticagrelor sheds light into the complexity of studying the PAD population and the continued need to meticulously design trials to investigate the optimal therapies. The topics that will be discussed in this review include the role of antiplatelet therapy in the management of patients with PAD, a review of the EUCLID trial results and the important factors to be considered in interpreting the surprising results, and promising recent ongoing clinical trials assessing therapies in the treatment of patients with PAD. © 2018 Wiley Periodicals, Inc.

Identification of two novel KIF5A mutations in hereditary spastic paraplegia associated with mild peripheral neuropathy.

PubMed

López, Eva; Casasnovas, Carlos; Giménez, Javier; Santamaría, Raúl; Terrazas, Jesús M; Volpini, Víctor

2015-11-15

Spastic paraplegia type 10 (SPG10) is a rare form of autosomal dominant hereditary spastic paraplegia (AD-HSP) due to mutations in KIF5A, a gene encoding the neuronal kinesin heavy-chain involved in axonal transport. KIF5A mutations have been associated with a wide clinical spectrum, ranging from pure HSP to isolated peripheral nerve involvement or complicated HSP phenotypes. Most KIF5A mutations are clustered in the motor domain of the protein that is necessary for microtubule interaction. Here we describe two Spanish families with an adult onset complicated AD-HSP in which neurological studies revealed a mild sensory neuropathy. Intention tremor was also present in both families. Molecular genetic analysis identified two novel mutations c.773 C>T and c.833 C>T in the KIF5A gene resulting in the P258L and P278L substitutions respectively. Both were located in the highly conserved kinesin motor domain of the protein which has previously been identified as a hot spot for KIF5A mutations. This study adds to the evidence associating the known occurrence of mild peripheral neuropathy in the adult onset SPG10 type of AD-HSP. Copyright © 2015 Elsevier B.V. All rights reserved.

Dysregulation of ErbB Receptor Trafficking and Signaling in Demyelinating Charcot-Marie-Tooth Disease

PubMed Central

Lee, Samuel M.; Chin, Lih-Shen; Li, Lian

2016-01-01

Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy with the majority of cases involving demyelination of peripheral nerves. The pathogenic mechanisms of demyelinating CMT remain unclear, and no effective therapy currently exists for this disease. The discovery that mutations in different genes can cause a similar phenotype of demyelinating peripheral neuropathy raises the possibility that there may be convergent mechanisms leading to demyelinating CMT pathogenesis. Increasing evidence indicates that ErbB receptor-mediated signaling plays a major role in the control of Schwann cell-axon communication and myelination in the peripheral nervous system. Recent studies reveal that several demyelinating CMT-linked proteins are novel regulators of endocytic trafficking and/or phosphoinositide metabolism that may affect ErbB receptor signaling. Emerging data have begun to suggest that dysregulation of ErbB receptor trafficking and signaling in Schwann cells may represent a common pathogenic mechanism in multiple subtypes of demyelinating CMT. In this review, we focus on the roles of ErbB receptor trafficking and signaling in regulation of peripheral nerve myelination and discuss the emerging evidence supporting the potential involvement of altered ErbB receptor trafficking and signaling in demyelinating CMT pathogenesis and the possibility of modulating these trafficking and signaling processes for treating demyelinating peripheral neuropathy. PMID:26732592

Dysregulation of ErbB Receptor Trafficking and Signaling in Demyelinating Charcot-Marie-Tooth Disease.

PubMed

Lee, Samuel M; Chin, Lih-Shen; Li, Lian

2017-01-01

Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy with the majority of cases involving demyelination of peripheral nerves. The pathogenic mechanisms of demyelinating CMT remain unclear, and no effective therapy currently exists for this disease. The discovery that mutations in different genes can cause a similar phenotype of demyelinating peripheral neuropathy raises the possibility that there may be convergent mechanisms leading to demyelinating CMT pathogenesis. Increasing evidence indicates that ErbB receptor-mediated signaling plays a major role in the control of Schwann cell-axon communication and myelination in the peripheral nervous system. Recent studies reveal that several demyelinating CMT-linked proteins are novel regulators of endocytic trafficking and/or phosphoinositide metabolism that may affect ErbB receptor signaling. Emerging data have begun to suggest that dysregulation of ErbB receptor trafficking and signaling in Schwann cells may represent a common pathogenic mechanism in multiple subtypes of demyelinating CMT. In this review, we focus on the roles of ErbB receptor trafficking and signaling in regulation of peripheral nerve myelination and discuss the emerging evidence supporting the potential involvement of altered ErbB receptor trafficking and signaling in demyelinating CMT pathogenesis and the possibility of modulating these trafficking and signaling processes for treating demyelinating peripheral neuropathy.

Peptide vaccination of patients with metastatic melanoma: improved clinical outcome in patients demonstrating effective immunization.

PubMed

Markovic, Svetomir N; Suman, Vera J; Ingle, James N; Kaur, Judith S; Pitot, Henry C; Loprinzi, Charles L; Rao, Ravi D; Creagan, Edward T; Pittelkow, Mark R; Allred, Jakob B; Nevala, Wendy K; Celis, Esteban

2006-08-01

Therapeutic peptide vaccines for melanoma continue to only demonstrate anecdotal success. We set out to evaluate the impact of low-dose GM-CSF emulsified in Montanide ISA-51 on the immunogenicity of HLA-A2 restricted melanoma differentiation antigen peptide vaccines (MART-1, gp100 and tyrosinase) administered in separate subcutaneous injections. We conducted a randomized phase II clinical trial of HLA-A2+ patients with metastatic melanoma that were immunized every 3 weeks with one of the following vaccine preparations: (A) peptides + Montanide ISA-51; (B) peptides + Montanide ISA-51 + GM-CSF (10 microg); (C) peptides + Montanide ISA-51 + GM-CSF (50 microg). Immunization efficacy was determined by quantification of vaccine specific tetramer positive cytotoxic T cells in peripheral blood. Global assessment of immune competence was ascertained using DTH testing to common recall antigens as well as peripheral blood immunophenotyping. Twenty-five eligible patients were equally distributed across all 3 treatment groups. Only 9 patients demonstrated evidence of immunization. Most commonly, immune response was achieved to the gp100 peptide. The addition of low-dose GM-CSF did not impact immunization efficacy. DTH reactivity to Candida appeared predictive of successful immunization. Successful immunization with the peptide vaccines was associated with improved clinical outcomes. The addition of low dose GM-CSF to peptide vaccines did not enhance immunogenicity. Higher doses of GM-CSF may be needed to achieve this effect and this is a testable hypothesis. Likewise, better patient selection based on immunologic status (DTH reactivity) may be helpful to better understand the clinical impact of therapeutic cancer vaccines.

Acute Modulation of Brain Connectivity in Parkinson Disease after Automatic Mechanical Peripheral Stimulation: A Pilot Study

PubMed Central

Piervincenzi, Claudia; Galli, Manuela; Melgari, Jean Marc; Salomone, Gaetano; Sale, Patrizio; Mallio, Carlo Augusto; Carducci, Filippo; Stocchi, Fabrizio

2015-01-01

Objective The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease. Methods Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition. Results Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79). Conclusions Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration. Classification of Evidence This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest. Trial Registration Clinical Trials.gov NCT01815281 PMID:26469868

Viral vector mediated continuous expression of interleukin-10 in DRG alleviates pain in type 1 diabetic animals.

PubMed

Thakur, Vikram; Gonzalez, Mayra; Pennington, Kristen; Chattopadhyay, Munmun

2016-04-01

Painful diabetic neuropathy is a common and difficult to treat complication of diabetes. A growing body of evidence implicates the role of inflammatory mediators in the damage to the peripheral axons and in the pathogenesis of neuropathic pain. Increased expression of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α in the peripheral nervous system suggests the possibility of change in pain perception in diabetes. In this study we investigated that continuous delivery of IL10 in the nerve fibers achieved by HSV vector mediated transduction of dorsal root ganglion (DRG) in animals with Type 1 diabetes, blocks the nociceptive and stress responses in the DRG neurons by reducing IL1β expression along with inhibition of phosphorylation of p38 MAPK (mitogen-activated protein kinase) and protein kinase C (PKC). The continuous expression of IL10 also alters Toll like receptor (TLR)-4 expression in the DRG with increased expression of heat shock protein (HSP)-70 in conjunction with the reduction of pain. Taken together, this study suggests that macrophage activation in the peripheral nervous system may be involved in the pathogenesis of pain in Type 1 diabetes and therapeutic benefits of HSV mediated local expression of IL10 in the DRG with the reduction of a number of proinflammatory cytokines, subsequently inhibits the development of painful neuropathy along with a decrease in stress associated markers in the DRG. This basic and preclinical study provides an important evidence for a novel treatment strategy that could lead to a clinical trial for what is currently a treatment resistant complication of diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Renal cell carcinoma with Xp11.2 translocation in a 7-year-old boy.

PubMed

Jayasinghe, C; Siegler, N; Leuschner, I; Fleischhack, G; Born, M; Müller, A M

2010-05-01

More than 90% of pediatric renal tumors are nephroblastomas while renal cell carcinomas (RCC) are rare in children (< 5%). According to the clinical diagnoses of a nephroblastoma stage IV a 7-year-old boy with a kidney tumor and peripheral pulmonary lesion was preoperatively treated for 8 weeks with Vincristine, Actinomycin D and Adriamycin. The resected kidney displayed a RCC with Xp11.2 translocation. There was no tumor regression and the pulmonary lesion was no longer detectable. Hence chemotherapy was put to a halt. Fine needle aspiration biopsy (FNA) would have allowed to adjust the tumor subtype. Prognosis of pediatric RCC with translocation seems more favourable than without translocation though definitive evidence will only be possible by documentation in a clinical diagnose-related register.

Olfactory epithelium: Cells, clinical disorders, and insights from an adult stem cell niche

PubMed Central

Choi, Rhea

2018-01-01

Disorders causing a loss of the sense of smell remain a therapeutic challenge. Basic research has, however, greatly expanded our knowledge of the organization and function of the olfactory system. This review describes advances in our understanding of the cellular components of the peripheral olfactory system, specifically the olfactory epithelium in the nose. The article discusses recent findings regarding the mechanisms involved in regeneration and cellular renewal from basal stem cells in the adult olfactory epithelium, considering the strategies involved in embryonic olfactory development and insights from research on other stem cell niches. In the context of clinical conditions causing anosmia, the current view of adult olfactory neurogenesis, tissue homeostasis, and failures in these processes is considered, along with current and future treatment strategies. Level of Evidence NA PMID:29492466

Clinical efficacy of aconitum-containing traditional Chinese medicine for diabetic peripheral neuropathic pain.

PubMed

Feng, Ling; Liu, Wen-Ke; Deng, Lan; Tian, Jia-Xing; Tong, Xiao-Lin

2014-01-01

Diabetic peripheral neuropathy is a common chronic complication of diabetes. Routine clinical management uses analgesics to relieve pain in combination with drugs for nerve repair. The drugs are often not effective for the severe pain cases, and these western medications also have side effects. We report a more effective treatment of diabetic peripheral neuropathic pain using a high dose of a traditional Chinese medicine, aconitum (including both Radix aconite preparata and Radix aconite kusnezoffii), in combination with Huangqi Guizhi Wuwu Tang (i.e., astragalus, cassia twig, white peony root, and spatholobi). In order to achieve stronger analgesic effects, we increased the clinical dosage of aconitum from 15 to 120 g. The aconitum was boiled for 6-8 hours, and licorice was also used to reduce potential toxicities of aconitum. In the four reported cases, the patients' neuropathic pain was remarkably reduced and the EMG profile was also improved with this treatment regimen. Adverse reactions were not observed during the therapy. Thus, aconitum represents a promising and safe treatment for the well-being of patients and their diabetic peripheral neuropathic pain. Future controlled clinical trials using traditional Chinese medicines containing aconitum in treating the neuropathic pain are warranted.

Acupuncture, psyche and the placebo response.

PubMed

Enck, Paul; Klosterhalfen, Sibylle; Zipfel, Stephan

2010-10-28

With growing use of acupuncture treatment in various clinical conditions, the question has been posed whether the reported effects reflect specific mechanisms of acupuncture or whether they represent placebo responses, as they often are similar in effect size and resemble similarities to placebo analgesia and its mechanisms. We reviewed the available literature for different placebos (sham procedures) used to control the acupuncture effects, for moderators and potential biases in respective clinical trials, and for central and peripheral mechanisms involved that would allow differentiation of placebo effects from acupuncture and sham acupuncture effects. While the evidence is still limited, it seems that biological differences exist between a placebo response, e.g. in placebo analgesia, and analgesic response during acupunture that does not occur with sham acupuncture. It seems advisable that clinical trials should include potential biomarkers of acupuncture, e.g. measures of the autonomic nervous system function to verify that acupuncture and sham acupuncture are different despite similar clinical effects. Copyright © 2010 Elsevier B.V. All rights reserved.

Chemotherapy-Induced Peripheral Neuropathy in Long-term Survivors of Childhood Cancer: Clinical, Neurophysiological, Functional, and Patient-Reported Outcomes.

PubMed

Kandula, Tejaswi; Farrar, Michelle Anne; Cohn, Richard J; Mizrahi, David; Carey, Kate; Johnston, Karen; Kiernan, Matthew C; Krishnan, Arun V; Park, Susanna B

2018-05-14

In light of the excellent long-term survival of childhood cancer patients, it is imperative to screen for factors affecting health, function, and quality of life in long-term survivors. To comprehensively assess chemotherapy-induced peripheral neuropathy in childhood cancer survivors to define disease burden and functional effect and to inform screening recommendations. In this cross-sectional observational study, cancer survivors who were treated with chemotherapy for extracranial malignancy before age 17 years were recruited consecutively between April 2015 and December 2016 from a single tertiary hospital-based comprehensive cancer survivorship clinic and compared with healthy age-matched controls. Investigators were blinded to the type of chemotherapy. A total of 169 patients met inclusion criteria, of whom 48 (28.4%) were unable to be contacted or declined participation. Chemotherapy agents known to be toxic to peripheral nerves. The clinical peripheral neurological assessment using the Total Neuropathy Score was compared between recipients of different neurotoxic chemotherapy agents and control participants and was correlated with neurophysiological, functional, and patient-reported outcome measures. Of the 121 childhood cancer survivors included in this study, 65 (53.7%) were male, and the cohort underwent neurotoxicity assessments at a median (range) age of 16 (7-47) years, a median (range) 8.5 (1.5-29) years after treatment completion. Vinca alkaloids and platinum compounds were the main neurotoxic agents. Clinical abnormalities consistent with peripheral neuropathy were common, seen in 54 of 107 participants (50.5%) treated with neurotoxic chemotherapy (mean Total Neuropathy Score increase, 2.1; 95% CI, 1.4-2.9; P < .001), and were associated with lower limb predominant sensory axonal neuropathy (mean amplitude reduction, 5.8 μV; 95% CI, 2.8-8.8; P < .001). Functional deficits were seen in manual dexterity, distal sensation, and balance. Patient-reported outcomes demonstrating reduction in global quality of life and physical functioning were associated with the Total Neuropathy Score. Cisplatin produced long-term neurotoxicity more frequently than vinca alkaloids. Clinical abnormalities attributable to peripheral neuropathy were common in childhood cancer survivors and persisted long term, with concurrent deficits in patient-reported outcomes. Both the type of neurotoxic agent and a targeted clinical neurological assessment are important considerations when screening survivors for long-term neuropathy. Further development of peripheral neuropathy-specific pediatric assessment tools will aid research into neuroprotective and rehabilitative strategies.

Clinical, physiological and pathological characterisation of the sensory predominant peripheral neuropathy in copper deficiency.

PubMed

Taylor, Sean W; Laughlin, Ruple S; Kumar, Neeraj; Goodman, Brent; Klein, Christopher J; Dyck, Peter J; Dyck, P James B

2017-10-01

Myelopathy is considered the most common neurological complication of copper deficiency. Concurrent peripheral neuropathy has been recognised in association with copper deficiency but has not been well characterised. To characterise the clinical, physiological and pathological features of copper-deficient peripheral neuropathy. Patients with simultaneous copper deficiency (<0.78 μg/mL) and peripheral neuropathy seen at the Mayo Clinic from 1985 to 2005 were identified. 34 patients were identified (median age 55 years, range 36-78) including 24 women and 10 men. Myelopathy was found in 21 patients. Median serum copper level was 0.11 μg/mL (range 0-0.58). The most frequent clinical and electrophysiological pattern of neuropathy was a sensory predominant length-dependent peripheral neuropathy (71%). Somatosensory evoked potentials demonstrated central slowing supporting myelopathy (96%). Quantitative sensory testing demonstrated both small and large fibre involvement (100%). Autonomic reflex screens (77%) and thermoregulatory sweat test (67%) confirmed sudomotor dysfunction. 14 cutaneous nerve biopsies revealed loss of myelinated nerve fibres (86%), increased regenerative clusters (50%), increased rates of axonal degeneration (91%) and increased numbers of empty nerve strands (73%). 71% of biopsies demonstrated epineurial perivascular inflammation. An axonal, length-dependent sensory predominant peripheral neuropathy causing sensory ataxia is characteristic of copper deficiency usually co-occurring with myelopathy. Neurophysiological testing confirms involvement of large, greater than small fibres. The pathological findings suggest axonal degeneration and repair. Inflammatory infiltrates are common but are small and of doubtful pathological significance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Odontogenic keratocyst: a peripheral variant.

PubMed

Vij, H; Vij, R; Gupta, V; Sengupta, S

2011-01-01

Odontogenic keratocyst, which is developmental in nature, is an intraosseous lesion though on rare occasions it may occur in an extraosseous location. The extraosseous variant is referred to as peripheral odontogenic keratocyst. Though, clinically, peripheral odontogenic keratocyst resembles the gingival cyst of adults, it has histologic features that are pathognomonic of odontogenic keratocyst. This article presents a case of this uncommon entity.

Postoperative pain—from mechanisms to treatment

PubMed Central

Pogatzki-Zahn, Esther M.; Segelcke, Daniel; Schug, Stephan A.

2017-01-01

Abstract Introduction: Pain management after surgery continues to be suboptimal; there are several reasons including lack of translation of results from basic science studies and scientific clinical evidence into clinical praxis. Objectives: This review presents and discusses basic science findings and scientific evidence generated within the last 2 decades in the field of acute postoperative pain. Methods: In the first part of the review, we give an overview about studies that have investigated the pathophysiology of postoperative pain by using rodent models of incisional pain up to July 2016. The second focus of the review lies on treatment recommendations based on guidelines and clinical evidence, eg, by using the fourth edition of the “Acute Pain Management: Scientific Evidence” of the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine. Results: Preclinical studies in rodent models characterized responses of primary afferent nociceptors and dorsal horn neurons as one neural basis for pain behavior including resting pain, hyperalgesia, movement-evoked pain or anxiety- and depression-like behaviors after surgery. Furthermore, the role of certain receptors, mediators, and neurotransmitters involved in peripheral and central sensitization after incision were identified; many of these are very specific, relate to some modalities only, and are unique for incisional pain. Future treatment should focus on these targets to develop therapeutic agents that are effective for the treatment of postoperative pain as well as have few side effects. Furthermore, basic science findings translate well into results from clinical studies. Scientific evidence is able to point towards useful (and less useful) elements of multimodal analgesia able to reduce opioid consumption, improve pain management, and enhance recovery. Conclusion: Understanding basic mechanisms of postoperative pain to identify effective treatment strategies may improve patients' outcome after surgery. PMID:29392204

Current evidence of peripheral vestibular symptoms secondary to otitis media.

PubMed

Monsanto, Rafael da Costa; Kasemodel, Ana Luiza Papi; Tomaz, Andreza; Paparella, Michael M; Penido, Norma de Oliveira

2018-05-06

The association between otitis media and vestibular symptoms has been hypothesized in the past. Thus, in this study, we aimed to critically analyze (based in a systematic review of the literature) whether patients who have otitis media are at greater risk of developing vestibular impairment or not. We performed a systematic review of the literature and identified potentially relevant articles reporting vestibular symptoms and results of vestibular function tests in patients with otitis media through searches of the PubMED, Web of Science, Scopus, and Google Scholar databases. The quality of the final set of records was assessed using the "Newcaste-Ottawa Scale". Of the 2334 records searched, 43 met our inclusion and exclusion criteria, and those included 2250 patients. The records comprised 20 longitudinal studies, 21 cross-sectional studies, and 2 case reports. Regarding the type of otitis media studied, 25 examined vestibular impairment in otitis media with effusion, 6 acute otitis media, and 12 chronic otitis media. Results of anamnesis, clinical exams, and several vestibular function tests are reported and critically discussed. Most studies evaluating the association between otitis media and vestibular symptoms have potential methodological flaws. Clinical evidence suggests that patients with otitis media have increased chances for having vestibular symptoms, delayed acquisition of developmental milestones, and abnormalities in several vestibular function tests as compared with controls. Future studies with rigorous methodology aiming to assess the clinical significance (and prognostic factors) of the association between otitis media and vestibular impairment are warranted. Key message Several studies demonstrated long-term sequelae secondary to otitis media. However, the evidence supporting those assumptions are based in low-quality evidence. Thus, better structured studies are warranted to better understand the clinical relevance of such association.

Comprehensive Diabetes and Non-Communicable Disease Educator in the Low-Resource Settings.

PubMed

Bhattarai, M D

2016-01-01

The role of self-management education in diabetes and other major non-communicable diseases is clearly evident. To take care of and educate people with diabetes and other major NCD under the supervision of medical professionals and for education of other health care professionals, Comprehensive Diabetes and NCD Educators are needed in the routine service in peripheral health clinics and hospitals. The areas of training of CDNCD educator should match with the cost-effective interventions for diabetes and other major NCD that are feasible and planned for implementation in primary care in the low resource settings. Most of such interventions are part of diabetes education as required for Diabetes Self-Management Education programmes and traditional Diabetes Educator. The addition of use of inhaled steroids and bronchodilator in chronic respiratory disease and identification of presenting features of cancer, also required for many people with diabetes with various such common co-morbidities, will complete the areas of training of traditional Diabetes Educator as that of CDNCD Educator. Staff nurse and health assistants, who are as such already providing routine clinical service to all patients including with diabetes and major NCD in peripheral health clinics and hospitals, are most appropriate for CDNCD Educator training. The training of CDNCD Educator, like that of traditional Diabetes Educator, requires fulfilment of sufficient hours of practical work experience under supervision and achievement of the essential competencies entailing at least 6 month or more of intensive training schedules to be eligible to appear in its final certifying examination.

The syndrome of perisylvian polymicrogyria with congenital arthrogryposis.

PubMed

Poduri, Annapurna; Chitsazzadeh, Vida; D'Arrigo, Stefano; Fedrizzi, Ermellina; Pantaleoni, Chiara; Riva, Daria; Busse, Claudia; Küster, Helmut; Duplessis, Adre; Gaitanis, John; Sahin, Mustafa; Garganta, Cheryl; Topcu, Meral; Dies, Kira A; Barry, Brenda J; Partlow, Jennifer; Barkovich, A James; Walsh, Christopher A; Chang, Bernard S

2010-08-01

Bilateral perisylvian polymicrogyria (BPP) is a well-recognized malformation of cortical development commonly associated with epilepsy, cognitive impairment, and oromotor apraxia. Reports have suggested the association of BPP with arthrogryposis multiplex congenita. We sought to investigate the clinical, electrophysiological, and neuroradiological features of this combined syndrome to determine if there are unique features that distinguish BPP with arthrogryposis from BPP alone. Cases of BPP with congenital arthrogryposis were identified from a large research database of individuals with polymicrogyria. Clinical features (including oromotor function, seizures, and joint contractures), MR brain imaging, and results of neuromuscular testing were reviewed. Ten cases of BPP with congenital arthrogryposis were identified. Most cases had some degree of oromotor apraxia. Only a few had seizures, but a majority of cases were still young children. Electrophysiological studies provided evidence for lower motor neuron or peripheral nervous system involvement. On brain imaging, bilateral polymicrogyria (PMG) centered along the Sylvian fissures was seen, with variable extension frontally or parietally; no other cortical malformations were present. We did not identify obvious neuroimaging features that distinguish this syndrome from that of BPP without arthrogryposis. The clinical and neuroimaging features of the syndrome of BPP with congenital arthrogryposis appear similar to those seen in cases of isolated BPP without joint contractures, but electrophysiological studies often demonstrate coexistent lower motor neuron or peripheral nervous system pathology. These findings suggest that BPP with arthrogryposis may have a genetic etiology with effects at two levels of the neuraxis. Copyright 2009 Elsevier B.V. All rights reserved.

Chronic post-traumatic headache: clinical findings and possible mechanisms

PubMed Central

Defrin, Ruth

2014-01-01

Chronic post-traumatic headache (CPTHA), the most frequent complaint after traumatic brain injury (TBI), dramatically affects quality of life and function. Despite its high prevalence and persistence, the mechanism of CPTHA is poorly understood. This literature review aimed to analyze the results of studies assessing the characteristics and sensory profile of CPTHA in order to shed light on its possible underlying mechanisms. The search for English language articles published between 1960 and 2013 was conducted in MEDLINE, CINAHL, and PubMed. Studies assessing clinical features of headache after TBI as well as studies conducting quantitative somatosensory testing (QST) in individuals with CPTHA and in individuals suffering from other types of pain were included. Studies on animal models of pain following damage to peripheral tissues and to the peripheral and central nervous system were also included. The clinical features of CPTHA resembled those of primary headache, especially tension-type and migraine headache. Positive and negative signs were prevalent among individuals with CPTHA, in both the head and in other body regions, suggesting the presence of local (cranial) mechanical hypersensitivity, together with generalized thermal hypoesthesia and hypoalgesia. Evidence of dysfunctional pain modulation was also observed. Chronic post-traumatic headache can result from damage to intra- and pericranial tissues that caused chronic sensitization of these tissues. Alternatively, although not mutually exclusive, CPTHA might possibly be a form of central pain due to damage to brain structures involved in pain processing. These, other possibilities, as well as risk factors for CPTHA are discussed at length. PMID:24976746

B Cell-Directed Therapeutics in Multiple Sclerosis: Rationale and Clinical Evidence.

PubMed

Kinzel, Silke; Weber, Martin S

2016-12-01

Over the last decade, evidence condensed that B cells, B cell-derived plasma cells and antibodies play a key role in the pathogenesis and progression of multiple sclerosis (MS). In many patients with MS, peripheral B cells show signs of chronic activation; within the cerebrospinal fluid clonally expanded plasma cells produce oligoclonal immunoglobulins, which remain a hallmark diagnostic finding. Confirming the clinical relevance of these immunological alterations, recent trials testing anti-CD20-mediated depletion of peripheral B cells showed an instantaneous halt in development of new central nervous system lesions and occurrence of relapses. Notwithstanding this enormous success, not all B cells or B cell subsets may contribute in a pathogenic manner, and may, in contrast, exert anti-inflammatory and, thus, therapeutically desirable properties in MS. Naïve B cells, in MS patients similar to healthy controls, are a relevant source of regulatory cytokines such as interleukin-10, which dampens the activity of other immune cells and promotes recovery from acute disease flares in experimental MS models. In this review, we describe in detail pathogenic but also regulatory properties of B and plasma cells in the context of MS and its animal model experimental autoimmune encephalomyelitis. In the second part, we review what impact current and future therapies may have on these B cell properties. Within this section, we focus on the highly encouraging data on anti-CD20 antibodies as future therapy for MS. Lastly, we discuss how B cell-directed therapy in MS could be possibly advanced even further in regard to efficacy and safety by integrating the emerging information on B cell regulation in MS into future therapeutic strategies.

Impact of high iron intake on cognition and neurodegeneration in humans and in animal models: a systematic review.

PubMed

Agrawal, Sonal; Berggren, Kiersten L; Marks, Eileen; Fox, Jonathan H

2017-06-01

Accumulation of brain iron is linked to aging and protein-misfolding neurodegenerative diseases. High iron intake may influence important brain health outcomes in later life. The aim of this systematic review was to examine evidence from animal and human studies of the effects of high iron intake or peripheral iron status on adult cognition, brain aging, and neurodegeneration. MEDLINE, Scopus, CAB Abstracts, the Cochrane Central Register of Clinical Trials, and OpenGrey databases were searched. Studies investigating the effect of elevated iron intake at all postnatal life stages in mammalian models and humans on measures of adult brain health were included. Data were extracted and evaluated by two authors independently, with discrepancies resolved by discussion. Neurodegenerative disease diagnosis and/or behavioral/cognitive, biochemical, and brain morphologic findings were used to study the effects of iron intake or peripheral iron status on brain health. Risk of bias was assessed for animal and human studies. PRISMA guidelines for reporting systematic reviews were followed. Thirty-four preclinical and 14 clinical studies were identified from database searches. Thirty-three preclinical studies provided evidence supporting an adverse effect of nutritionally relevant high iron intake in neonates on brain-health-related outcomes in adults. Human studies varied considerably in design, quality, and findings; none investigated the effects of high iron intake in neonates/infants. Human studies are needed to verify whether dietary iron intake levels used in neonates/infants to prevent iron deficiency have effects on brain aging and neurodegenerative disease outcomes. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute.

Pharmacological Approach for Managing Pain in Irritable Bowel Syndrome: A Review Article

PubMed Central

Chen, Longtu; Ilham, Sheikh J.; Feng, Bin

2017-01-01

Context Visceral pain is a leading symptom for patients with irritable bowel syndrome (IBS) that affects 10% - 20 % of the world population. Conventional pharmacological treatments to manage IBS-related visceral pain is unsatisfactory. Recently, medications have emerged to treat IBS patients by targeting the gastrointestinal (GI) tract and peripheral nerves to alleviate visceral pain while avoiding adverse effects on the central nervous system (CNS). Several investigational drugs for IBS also target the periphery with minimal CNS effects. Evidence of Acquisition In this paper, reputable internet databases from 1960 - 2016 were searched including Pubmed and ClinicalTrials.org, and 97 original articles analyzed. Search was performed based on the following keywords and combinations: irritable bowel syndrome, clinical trial, pain, visceral pain, narcotics, opioid, chloride channel, neuropathy, primary afferent, intestine, microbiota, gut barrier, inflammation, diarrhea, constipation, serotonin, visceral hypersensitivity, nociceptor, sensitization, hyperalgesia. Results Certain conventional pain managing drugs do not effectively improve IBS symptoms, including NSAIDs, acetaminophen, aspirin, and various narcotics. Anxiolytic and antidepressant drugs (Benzodiazepines, TCAs, SSRI and SNRI) can attenuate pain in IBS patients with relevant comorbidities. Clonidine, gabapentin and pregabalin can moderately improve IBS symptoms. Lubiprostone relieves constipation predominant IBS (IBS-C) while loperamide improves diarrhea predominant IBS (IBS-D). Alosetron, granisetron and ondansetron can generally treat pain in IBS-D patients, of which alosetron needs to be used with caution due to cardiovascular toxicity. The optimal drugs for managing pain in IBS-D and IBS-C appear to be eluxadoline and linaclotide, respectively, both of which target peripheral GI tract. Conclusions Conventional pain managing drugs are in general not suitable for treating IBS pain. Medications that target the GI tract and peripheral nerves have better therapeutic profiles by limiting adverse CNS effects. PMID:28824858

Evidence for functional inter-relationships between FOXP3, leukaemia inhibitory factor, and axotrophin/MARCH-7 in transplantation tolerance.

PubMed

Muthukumarana, Poorni A D S; Lyons, Gary E; Miura, Yuji; Thompson, Lorraine H; Watson, Tracy; Green, Colin J; Shurey, Sandra; Hess, Allan D; Rosengard, Bruce R; Metcalfe, Su M

2006-12-20

In an ex vivo mouse model, regulatory transplantation tolerance is not only linked to Foxp3, but also to release of leukaemia inhibitory factor (LIF) and to expression of axotrophin (also known as MARCH-7), a putative ubiquitin E3 ligase associated with feedback control of T cell activation and of T cell-derived LIF. Given this coordinate correlation with tolerance, we now ask if Foxp3 expression is influenced by LIF or by axotrophin. In spleen cells from allo-rejected mice we found that exogenous LIF reduced interferon gamma release in response to donor antigen by 50%, but LIF had no direct effect on levels of Foxp3 protein in allo-primed cells that were either tolerant, or aggressive, for donor antigen. However, we did find an effect of axotrophin on Foxp3: in the axotrophin null mouse, thymic Foxp3 transcripts were reduced compared to axotrophin wildtype littermates. To test whether these findings in the mouse were of potential significance in man we measured transcript levels of axotrophin and LIF in peripheral blood cell samples collected for a recently published clinical study concerning haematopoietic stem cell recipients. In controls, human peripheral blood CD4+CD25+cells contained significantly more FOXP3 and axotrophin than CD4+CD25-cells. In bone marrow autograft recipients, where peripheral blood cell samples directly represent both the grafted tissue and the immune response, both FOXP3 and axotrophin negatively correlated with graft versus host disease (GVHD). These data suggest that (i) thymic Foxp3+T cell development is influenced by axotrophin; and (ii) clinical auto-GVHD inversely correlates with axotrophin transcript expression as has been previously reported for FOXP3.

Implementing core NICE guidelines for osteoarthritis in primary care with a model consultation (MOSAICS): a cluster randomised controlled trial.

PubMed

Dziedzic, K S; Healey, E L; Porcheret, M; Afolabi, E K; Lewis, M; Morden, A; Jinks, C; McHugh, G A; Ryan, S; Finney, A; Main, C; Edwards, J J; Paskins, Z; Pushpa-Rajah, A; Hay, E M

2018-01-01

To determine the effectiveness of a model osteoarthritis consultation, compared with usual care, on physical function and uptake of National Institute for Health and Care Excellence (NICE) osteoarthritis recommendations, in adults ≥45 years consulting with peripheral joint pain in UK general practice. Two-arm cluster-randomised controlled trial with baseline health survey. Eight general practices in England. 525 adults ≥45 years consulting for peripheral joint pain, amongst 28,443 population survey recipients. Four intervention practices delivered the model osteoarthritis consultation to patients consulting with peripheral joint pain; four control practices continued usual care. The primary clinical outcome of the trial was the SF-12 physical component score (PCS) at 6 months; the main secondary outcome was uptake of NICE core recommendations by 6 months, measured by osteoarthritis quality indicators. A Linear Mixed Model was used to analyse clinical outcome data (SF-12 PCS). Differences in quality indicator outcomes were assessed using logistic regression. 525 eligible participants were enrolled (mean age 67.3 years, SD 10.5; 59.6% female): 288 from intervention and 237 from control practices. There were no statistically significant differences in SF-12 PCS: mean difference at the 6-month primary endpoint was -0.37 (95% CI -2.32, 1.57). Uptake of core NICE recommendations by 6 months was statistically significantly higher in the intervention arm compared with control: e.g., increased written exercise information, 20.5% (7.9, 28.3). Whilst uptake of core NICE recommendations was increased, there was no evidence of benefit of this intervention, as delivered in this pragmatic randomised trial, on the primary outcome of physical functioning at 6 months. ISRCTN06984617. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Ghrelin: Central and Peripheral Implications in Anorexia Nervosa

PubMed Central

Méquinion, Mathieu; Langlet, Fanny; Zgheib, Sara; Dickson, Suzanne; Dehouck, Bénédicte; Chauveau, Christophe; Viltart, Odile

2012-01-01

Increasing clinical and therapeutic interest in the neurobiology of eating disorders reflects their dramatic impact on health. Chronic food restriction resulting in severe weight loss is a major symptom described in restrictive anorexia nervosa (AN) patients, and they also suffer from metabolic disturbances, infertility, osteopenia, and osteoporosis. Restrictive AN, mostly observed in young women, is the third largest cause of chronic illness in teenagers of industrialized countries. From a neurobiological perspective, AN-linked behaviors can be considered an adaptation that permits the endurance of reduced energy supply, involving central and/or peripheral reprograming. The severe weight loss observed in AN patients is accompanied by significant changes in hormones involved in energy balance, feeding behavior, and bone formation, all of which can be replicated in animals models. Increasing evidence suggests that AN could be an addictive behavior disorder, potentially linking defects in the reward mechanism with suppressed food intake, heightened physical activity, and mood disorder. Surprisingly, the plasma levels of ghrelin, an orexigenic hormone that drives food-motivated behavior, are increased. This increase in plasma ghrelin levels seems paradoxical in light of the restrained eating adopted by AN patients, and may rather result from an adaptation to the disease. The aim of this review is to describe the role played by ghrelin in AN focusing on its central vs. peripheral actions. In AN patients and in rodent AN models, chronic food restriction induces profound alterations in the « ghrelin » signaling that leads to the development of inappropriate behaviors like hyperactivity or addiction to food starvation and therefore a greater depletion in energy reserves. The question of a transient insensitivity to ghrelin and/or a potential metabolic reprograming is discussed in regard of new clinical treatments currently investigated. PMID:23549309

PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia.

PubMed

Di Biase, M A; Zalesky, A; O'keefe, G; Laskaris, L; Baune, B T; Weickert, C S; Olver, J; McGorry, P D; Amminger, G P; Nelson, B; Scott, A M; Hickie, I; Banati, R; Turkheimer, F; Yaqub, M; Everall, I P; Pantelis, C; Cropley, V

2017-08-29

We examined putative microglial activation as a function of illness course in schizophrenia. Microglial activity was quantified using [ 11 C](R)-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide ( 11 C-(R)-PK11195) positron emission tomography (PET) in: (i) 10 individuals at ultra-high risk (UHR) of psychosis; (ii) 18 patients recently diagnosed with schizophrenia; (iii) 15 patients chronically ill with schizophrenia; and, (iv) 27 age-matched healthy controls. Regional-binding potential (BP ND ) was calculated using the simplified reference-tissue model with four alternative reference inputs. The UHR, recent-onset and chronic patient groups were compared to age-matched healthy control groups to examine between-group BP ND differences in 6 regions: dorsal frontal, orbital frontal, anterior cingulate, medial temporal, thalamus and insula. Correlation analysis tested for BP ND associations with gray matter volume, peripheral cytokines and clinical variables. The null hypothesis of equality in BP ND between patients (UHR, recent-onset and chronic) and respective healthy control groups (younger and older) was not rejected for any group comparison or region. Across all subjects, BP ND was positively correlated to age in the thalamus (r=0.43, P=0.008, false discovery rate). No correlations with regional gray matter, peripheral cytokine levels or clinical symptoms were detected. We therefore found no evidence of microglial activation in groups of individuals at high risk, recently diagnosed or chronically ill with schizophrenia. While the possibility of 11 C-(R)-PK11195-binding differences in certain patient subgroups remains, the patient cohorts in our study, who also displayed normal peripheral cytokine profiles, do not substantiate the assumption of microglial activation in schizophrenia as a regular and defining feature, as measured by 11 C-(R)-PK11195 BP ND .

Central attention is serial, but midlevel and peripheral attention are parallel-A hypothesis.

PubMed

Tamber-Rosenau, Benjamin J; Marois, René

2016-10-01

In this brief review, we argue that attention operates along a hierarchy from peripheral through central mechanisms. We further argue that these mechanisms are distinguished not just by their functional roles in cognition, but also by a distinction between serial mechanisms (associated with central attention) and parallel mechanisms (associated with midlevel and peripheral attention). In particular, we suggest that peripheral attentional deployments in distinct representational systems may be maintained simultaneously with little or no interference, but that the serial nature of central attention means that even tasks that largely rely on distinct representational systems will come into conflict when central attention is demanded. We go on to review both the behavioral and neural evidence for this prediction. We conclude that even though the existing evidence mostly favors our account of serial central and parallel noncentral attention, we know of no experiment that has conclusively borne out these claims. As such, this article offers a framework of attentional mechanisms that will aid in guiding future research on this topic.

Functional Biomarkers of Depression: Diagnosis, Treatment, and Pathophysiology

PubMed Central

Schmidt, Heath D; Shelton, Richard C; Duman, Ronald S

2011-01-01

Major depressive disorder (MDD) is a heterogeneous illness for which there are currently no effective methods to objectively assess severity, endophenotypes, or response to treatment. Increasing evidence suggests that circulating levels of peripheral/serum growth factors and cytokines are altered in patients with MDD, and that antidepressant treatments reverse or normalize these effects. Furthermore, there is a large body of literature demonstrating that MDD is associated with changes in endocrine and metabolic factors. Here we provide a brief overview of the evidence that peripheral growth factors, pro-inflammatory cytokines, endocrine factors, and metabolic markers contribute to the pathophysiology of MDD and antidepressant response. Recent preclinical studies demonstrating that peripheral growth factors and cytokines influence brain function and behavior are also discussed along with their implications for diagnosing and treating patients with MDD. Together, these studies highlight the need to develop a biomarker panel for depression that aims to profile diverse peripheral factors that together provide a biological signature of MDD subtypes as well as treatment response. PMID:21814182

Glucagon-like peptide 1 interacts with ghrelin and leptin to regulate glucose metabolism and food intake through vagal afferent neuron signaling.

PubMed

Ronveaux, Charlotte C; Tomé, Daniel; Raybould, Helen E

2015-04-01

Emerging evidence has suggested a possible physiologic role for peripheral glucagon-like peptide 1 (GLP-1) in regulating glucose metabolism and food intake. The likely site of action of GLP-1 is on vagal afferent neurons (VANs). The vagal afferent pathway is the major neural pathway by which information about ingested nutrients reaches the central nervous system and influences feeding behavior. Peripheral GLP-1 acts on VANs to inhibit food intake. The mechanism of the GLP-1 receptor (GLP-1R) is unlike other gut-derived receptors; GLP-1Rs change their cellular localization according to feeding status rather than their protein concentrations. It is possible that several gut peptides are involved in mediating GLP-1R translocation. The mechanism of peripheral GLP-1R translocation still needs to be elucidated. We review data supporting the role of peripheral GLP-1 acting on VANs in influencing glucose homeostasis and feeding behavior. We highlight evidence demonstrating that GLP-1 interacts with ghrelin and leptin to induce satiation. Our aim was to understand the mechanism of peripheral GLP-1 in the development of noninvasive antiobesity treatments. © 2015 American Society for Nutrition.

Blood borne hormones in a cross-talk between peripheral and brain mechanisms regulating blood pressure, the role of circumventricular organs.

PubMed

Ufnal, Marcin; Skrzypecki, Janusz

2014-04-01

Accumulating evidence suggests that blood borne hormones modulate brain mechanisms regulating blood pressure. This appears to be mediated by the circumventricular organs which are located in the walls of the brain ventricular system and lack the blood-brain barrier. Recent evidence shows that neurons of the circumventricular organs express receptors for the majority of cardiovascular hormones. Intracerebroventricular infusions of hormones and their antagonists is one approach to evaluate the influence of blood borne hormones on the neural mechanisms regulating arterial blood pressure. Interestingly, there is no clear correlation between peripheral and central effects of cardiovascular hormones. For example, angiotensin II increases blood pressure acting peripherally and centrally, whereas peripherally acting pressor catecholamines decrease blood pressure when infused intracerebroventricularly. The physiological role of such dual hemodynamic responses has not yet been clarified. In the paper we review studies on hemodynamic effects of catecholamines, neuropeptide Y, angiotensin II, aldosterone, natriuretic peptides, endothelins, histamine and bradykinin in the context of their role in a cross-talk between peripheral and brain mechanisms involved in the regulation of arterial blood pressure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Candidate immune biomarkers for radioimmunotherapy.

PubMed

Levy, Antonin; Nigro, Giulia; Sansonetti, Philippe J; Deutsch, Eric

2017-08-01

Newly available immune checkpoint blockers (ICBs), capable to revert tumor immune tolerance, are revolutionizing the anticancer armamentarium. Recent evidence also established that ionizing radiation (IR) could produce antitumor immune responses, and may as well synergize with ICBs. Multiple radioimmunotherapy combinations are thenceforth currently assessed in early clinical trials. Past examples have highlighted the need for treatment personalization, and there is an unmet need to decipher immunological biomarkers that could allow selecting patients who could benefit from these promising but expensive associations. Recent studies have identified potential predictive and prognostic immune assays at the cellular (tumor microenvironment composition), genomic (mutational/neoantigen load), and peripheral blood levels. Within this review, we collected the available evidence regarding potential personalized immune biomarker-directed radiation therapy strategies that might be used for patient selection in the era of radioimmunotherapy. Copyright © 2017. Published by Elsevier B.V.

Lupus pernio: a clinico-radiological study of thirty-five cases.

PubMed

Spiteri, M A; Matthey, F; Gordon, T; Carstairs, L S; James, D G

1985-03-01

Thirty-five patients with lupus pernio were observed in a series of 818 patients with clinical and histological evidence of sarcoidosis. This analysis provides the natural history of lupus pernio and its associated clinico-radiographic features. There was intrathoracic involvement in 74% of patients, upper respiratory tract disease in 54%, reticulo-endothelial involvement in 54%, bone cysts in 43% and ocular lesions in 37%. It predominated in West Indies-born women. Histological confirmation was easily obtained by nasal mucosal biopsy and this could be repeated serially to evaluate the response to various treatments. Nasal bone radiographs showed destruction of the nasal bones, porosis and alteration in bone texture. Peripheral bone cysts were evident in 50% of patients who were radiographed, and in about 50% of these patients, the cysts were found in both hands and feet.

Predicting health-related quality of life in cancer patients receiving chemotherapy: a structural equation approach using the self-control model.

PubMed

Park, Yu-Ri; Park, Eun-Young; Kim, Jung-Hee

2017-11-09

According to the self-control model, self-control works as a protective factor and a psychological resource. Although an understanding of the effect(s) of peripheral neuropathy on quality of life is important to healthcare professionals, previous studies do not facilitate broad comprehension in this regard. The purpose of this cross-sectional study was to test the multidimensional assumptions of quality of life of patients with cancer, with focus on their self-control. A structural equation model was tested on patients with cancer at the oncology clinic of a university hospital where patients received chemotherapy. A model was tested using structural equation modeling, which allows the researcher to find the empirical evidence by testing a measurement model and a structural model. The model comprised three variables, self-control, health related quality of life, and chemotherapy-induced peripheral neuropathy. Among the variables, self-control was the endogenous and mediating variable. The proposed models showed good fit indices. Self-control partially mediated chemotherapy-induced peripheral neuropathy and quality of life. It was found that the physical symptoms of peripheral neuropathy influenced health-related quality of life both indirectly and directly. Self-control plays a significant role in the protection and promotion of physical and mental health in various stressful situations, and thus, as a psychological resource, it plays a significant role in quality of life. Our results can be used to develop a quality of life model for patients receiving chemotherapy and as a theoretical foundation for the development of appropriate nursing interventions.

Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel

PubMed Central

2011-01-01

Background Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen. Methods An international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain. Results We describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e.g., angiokeratoma, corneal opacities) and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients. Conclusions Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with Fabry disease appears to be inadequate. PMID:21619592

Comparison of the effects of three oral bisphosphonate therapies on the peripheral skeleton in postmenopausal osteoporosis: the TRIO study.

PubMed

Paggiosi, M A; Peel, N; McCloskey, E; Walsh, J S; Eastell, R

2014-12-01

We compared the effects of oral alendronate, ibandronate and risedronate on the central and peripheral skeleton over 2 years. We report differences in effect on the central skeleton but not on the peripheral skeleton. Greater effects were observed for ibandronate (and alendronate) than risedronate at the spine but not the hip. Generally, comparative clinical trials of bisphosphonates have examined changes in bone within central skeletal regions. We have examined the effects of bisphosphonate treatment on the peripheral skeleton. We conducted a 2-year, open-label, parallel randomised control trial of three orally administered bisphosphonates, at their licensed dose, to examine and compare their effects on the peripheral skeleton using multiple modes of measurement. We studied 172 postmenopausal women (53-84 years) who had either a bone mineral density (BMD) T-score of  ≤ -2.5 at the spine and/or total hip or  < -1.0 at either site plus a previous low trauma fracture. Participants were randomised to receive either (i) ibandronate 150 mg/month, (ii) alendronate 70 mg/week or (iii) risedronate 35 mg/week, plus calcium (1,200 mg/day) and vitamin D (800 IU/day), for 2 years. Premenopausal women (33-40 years, n = 226) were studied to monitor device stability. We measured central BMD of the lumbar spine, total hip, total body and forearm using dual-energy X-ray absorptiometry. We measured calcaneus BMD (using dual-energy X-ray absorptiometry plus laser), radius and tibia BMD (using peripheral quantitative computed tomography), finger BMD (using radiographic absorptiometry), and phalangeal and calcaneal ultrasound variables (using quantitative ultrasound). Mixed effects regression models were used to evaluate effects of time and treatment allocation on BMD change. By 2 years, there were significant increases (p < 0.05) in central BMD sites (lumbar spine, total hip). In the peripheral skeleton, only significant changes in calcaneus BMD, 33 % total radius BMD and quantitative ultrasound (QUS)-2 broadband ultrasound attenuation (BUA) were evident for women receiving oral bisphosphonates. The increases in lumbar spine and total body BMD were greater with ibandronate and alendronate than with risedronate. Treatment effects on peripheral measurements did not differ between the three bisphosphonates.

The Effects of Physical Exercise on Fatty Liver Disease

PubMed Central

van der Windt, Dirk J.; Sud, Vikas; Zhang, Hongji; Tsung, Allan; Huang, Hai

2018-01-01

The increasing prevalence of obesity has made nonalcoholic fatty liver disease (NAFLD) the most common chronic liver disease. As a consequence, NAFLD and especially its inflammatory form nonalcoholic steatohepatitis (NASH) are the fastest increasing etiology of end-stage liver disease and hepatocellular carcinoma. Physical inactivity is related to the severity of fatty liver disease irrespective of body weight, supporting the hypothesis that increasing physical activity through exercise can improve fatty liver disease. This review summarizes the evidence for the effects of physical exercise on NAFLD and NASH. Several clinical trials have shown that both aerobic and resistance exercise reduce the hepatic fat content. From clinical and basic scientific studies, it is evident that exercise affects fatty liver disease through various pathways. Improved peripheral insulin resistance reduces the excess delivery of free fatty acids and glucose for free fatty acid synthesis to the liver. In the liver, exercise increases fatty acid oxidation, decreases fatty acid synthesis, and prevents mitochondrial and hepatocellular damage through a reduction of the release of damage-associated molecular patterns. In conclusion, physical exercise is a proven therapeutic strategy to improve fatty liver disease. PMID:29212576

Cross sectional study to evaluate the effect of duration of type 2 diabetes mellitus on the nerve conduction velocity in diabetic peripheral neuropathy.

PubMed

Hussain, Gauhar; Rizvi, S Aijaz Abbas; Singhal, Sangeeta; Zubair, Mohammad; Ahmad, Jamal

2014-01-01

To study the nerve conduction velocity in clinically undetectable and detectable peripheral neuropathy in type 2 diabetes mellitus with variable duration. This cross sectional study was conducted in diagnosed type 2 diabetes mellitus patients. They were divided in groups: Group I (n=37) with clinically detectable diabetic peripheral neuropathy of shorter duration and Group II (n=27) with clinically detectable diabetic peripheral neuropathy of longer duration. They were compared with T2DM patients (n=22) without clinical neuropathy. Clinical diagnosis was based on neuropathy symptom score (NSS) and neuropathy disability score (NDS) for signs. Nerve conduction velocity was measured in both upper and lower limbs. Median, ulnar, common peroneal and posterior tibial nerves were selected for motor nerve conduction study and median and sural nerves were selected for sensory nerve conduction study. The comparisons were done between nerve conduction velocities of motor and sensory nerves in patients of clinically detectable neuropathy and patients without neuropathy in type 2 diabetes mellitus population. This study showed significant electrophysiological changes with duration of disease. Nerve conduction velocities in lower limbs were significantly reduced even in patients of shorter duration with normal upper limb nerve conduction velocities. Diabetic neuropathy symptom score (NSS) and neuropathy disability score (NDS) can help in evaluation of diabetic sensorimotor polyneuropathy though nerve conduction study is more powerful test and can help in diagnosing cases of neuropathy. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Safety and Utility of Quantitative Sensory Testing among Adults with Sickle Cell Disease: Indicators of Neuropathic Pain?

PubMed Central

Ezenwa, Miriam O.; Molokie, Robert E.; Wang, Zaijie Jim; Yao, Yingwei; Suarez, Marie L.; Pullum, Cherese; Schlaeger, Judith M.; Fillingim, Roger B.; Wilkie, Diana J.

2014-01-01

Objectives Pain is the hallmark symptom of sickle cell disease (SCD), yet the types of pain that these patients experience, and the underlying mechanisms, have not been well characterized. The study purpose was to determine the safety and utility of a mechanical and thermal quantitative sensory testing (QST) protocol and the feasibility of utilizing neuropathic pain questionnaires among adults with SCD. Methods A convenience sample (N=25, 18 women, mean age 38.5 ± 12.5 [20–58 years]) completed self-report pain and quality-of-life tools. Subjects also underwent testing with the TSA-II NeuroSensory Analyzer and calibrated von Frey microfilaments. Results We found that the QST protocol was safe and did not stimulate a SCD pain crisis. There was evidence of central sensitization (n=15), peripheral sensitization (n=1), a mix of central and peripheral sensitization (n=8), or no sensitization (n=1). The neuropathic pain self-report tools were feasible with evidence of construct validity; 40% of the subjects reported S-LANSS scores that were indicative of neuropathic pain and had evidence of central, peripheral or mixed sensitization. Discussion The QST protocol can be safely conducted in adults with SCD and provides evidence of central or peripheral sensitization, which is consistent with a neuropathic component to SCD pain. These findings are novel, warrant a larger confirmatory study, and indicate the need for normative QST data from African American adults and older adults. PMID:25581383

Utility of an Abbreviated Dizziness Questionnaire to Differentiate between Causes of Vertigo and Guide Appropriate Referral: A Multicenter Prospective Blinded Study

PubMed Central

Roland, Lauren T.; Kallogjeri, Dorina; Sinks, Belinda C.; Rauch, Steven D.; Shepard, Neil T.; White, Judith A.; Goebel, Joel A.

2015-01-01

Objective Test performance of a focused dizziness questionnaire’s ability to discriminate between peripheral and non-peripheral causes of vertigo. Study Design Prospective multi-center Setting Four academic centers with experienced balance specialists Patients New dizzy patients Interventions A 32-question survey was given to participants. Balance specialists were blinded and a diagnosis was established for all participating patients within 6 months. Main outcomes Multinomial logistic regression was used to evaluate questionnaire performance in predicting final diagnosis and differentiating between peripheral and non-peripheral vertigo. Univariate and multivariable stepwise logistic regression were used to identify questions as significant predictors of the ultimate diagnosis. C-index was used to evaluate performance and discriminative power of the multivariable models. Results 437 patients participated in the study. Eight participants without confirmed diagnoses were excluded and 429 were included in the analysis. Multinomial regression revealed that the model had good overall predictive accuracy of 78.5% for the final diagnosis and 75.5% for differentiating between peripheral and non-peripheral vertigo. Univariate logistic regression identified significant predictors of three main categories of vertigo: peripheral, central and other. Predictors were entered into forward stepwise multivariable logistic regression. The discriminative power of the final models for peripheral, central and other causes were considered good as measured by c-indices of 0.75, 0.7 and 0.78, respectively. Conclusions This multicenter study demonstrates a focused dizziness questionnaire can accurately predict diagnosis for patients with chronic/relapsing dizziness referred to outpatient clinics. Additionally, this survey has significant capability to differentiate peripheral from non-peripheral causes of vertigo and may, in the future, serve as a screening tool for specialty referral. Clinical utility of this questionnaire to guide specialty referral is discussed. PMID:26485598

Chemotherapy-induced peripheral neuropathy: an update on the current understanding.

PubMed

Addington, James; Freimer, Miriam

2016-01-01

Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects.

Invasive and noninvasive assessment of pulmonic regurgitation: clinical, angiographic, phonocardiographic, echocardiographic, and Doppler ultrasound correlations.

PubMed

Chandraratna, P A; Wilson, D; Imaizumi, T; Ritter, W S; Aronow, W S

1982-06-01

Three patients with pulmonic regurgitation and no evidence of pulmonary hypertension were investigated. These patients had low pitched diastolic murmurs which increased on inspiration, evidence of connective tissue disease as manifested by lax joints and hyperextensible skin, and marked hilar dance which extended up to the peripheral vessels. Suprasternal echocardiography revealed dilatation and increased systolic expansion of the right pulmonary artery (RPA) (25% and 28%, respectively) in two patients; the third patient had a normal RPA dimension in diastole and a marked increase in diameter (88%) in systole. Thus, these three patients demonstrated hyperdistensibility of the RPA. The spectral signal from the pulsed doppler echocardiograph showed evidence of turbulent blood flow in diastole (wide dispersion of the dots) in the right ventricular outflow tract in all three patients. This pattern was indicative of pulmonic regurgitation. In summary, the combined use of echocardiography and Doppler ultrasound is useful in the evaluation of patients with pulmonic regurgitation.

How valuable is physical examination of the cardiovascular system?

PubMed

Elder, Andrew; Japp, Alan; Verghese, Abraham

2016-07-27

Physical examination of the cardiovascular system is central to contemporary teaching and practice in clinical medicine. Evidence about its value focuses on its diagnostic accuracy and varies widely in methodological quality and statistical power. This makes collation, analysis, and understanding of results difficult and limits their application to daily clinical practice. Specific factors affecting interpretation and clinical application include poor standardisation of observers' technique and training, the study of single signs rather than multiple signs or signs in combination with symptoms, and the tendency to compare physical examination directly with technological aids to diagnosis rather than explore diagnostic strategies that combine both. Other potential aspects of the value of physical examination, such as cost effectiveness or patients' perceptions, are poorly studied. This review summarises the evidence for the clinical value of physical examination of the cardiovascular system. The best was judged to relate to the detection and evaluation of valvular heart disease, the diagnosis and treatment of heart failure, the jugular venous pulse in the assessment of central venous pressure, and the detection of atrial fibrillation, peripheral arterial disease, impaired perfusion, and aortic and carotid disease. Although technological aids to diagnosis are likely to become even more widely available at the point of care, the evidence suggests that further research into the value of physical examination of the cardiovascular system is needed, particularly in low resource settings and as a potential means of limiting inappropriate overuse of technological aids to diagnosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The role of NMDA receptors in human eating behavior: evidence from a case of anti-NMDA receptor encephalitis.

PubMed

Perogamvros, Lampros; Schnider, Armin; Leemann, Beatrice

2012-06-01

Research in animal models has implicated N-methyl-D-aspartate (NMDA) receptors (NMDARs) in the control of food intake. Until now, these findings have been not replicated in humans. Here we describe a 22-year-old woman with anti-NMDAR encephalitis and no prior neurological or psychiatric history. Her clinical course was marked by successive eating disorders: anorexia followed by hyperphagia. We propose that, much as they do in other animals, NMDARs in humans interact with the neuroendocrine, homeostatic, and reward systems controlling food intake in the central and peripheral nervous system structures related to feeding and satiety.

Peripheral refractive correction and automated perimetric profiles.

PubMed

Wild, J M; Wood, J M; Crews, S J

1988-06-01

The effect of peripheral refractive error correction on the automated perimetric sensitivity profile was investigated on a sample of 10 clinically normal, experienced observers. Peripheral refractive error was determined at eccentricities of 0 degree, 20 degrees and 40 degrees along the temporal meridian of the right eye using the Canon Autoref R-1, an infra-red automated refractor, under the parametric conditions of the Octopus automated perimeter. Perimetric sensitivity was then undertaken at these eccentricities (stimulus sizes 0 and III) with and without the appropriate peripheral refractive correction using the Octopus 201 automated perimeter. Within the measurement limits of the experimental procedures employed, perimetric sensitivity was not influenced by peripheral refractive correction.

Hereditary motor and sensory neuropathy type VI with optic atrophy.

PubMed

Voo, Irene; Allf, Bryan E; Udar, Nitin; Silva-Garcia, Rosamaria; Vance, Jeffrey; Small, Kent W

2003-10-01

To present the detailed clinical findings of a large family with hereditary motor and sensory neuropathy type VI (HMSN VI), a syndrome featuring optic atrophy. Observational case series. A detailed history was obtained and physical examination was made of the extended family of the proband for evidence of neurologic dysfunction. The OPA1 gene was screened for mutations by direct DNA sequencing. Twelve of 97 family members examined are affected with signs of HMSN VI. Three other members have either optic atrophy or peripheral neuropathy, thus allowing an appreciation of the full clinical spectrum of disease. No mutations were found in the OPA1 gene. This family demonstrates the variable expressivity of this disorder as well as incomplete penetrance. This is the largest known family with HMSN VI. No association was found with changes in the OPA1 gene.

[Importance of electromiographic examination in diagnostification and monitoring of chronic inflammatory demyelinating polyneuropathy].

PubMed

Damjan, Igor; Cvijanović, Milan; Erak, Marko

2010-01-01

Polyneuropathies or peripheral neuropathies present a dysfunction or disease of larger number of peripheral nerves or their dysfunction. Considering their morbidity - mortality characteristics they present an important aspect in daily clinical practice. One particular polyneuropathy that deserves special review is chronic inflammatory demyelinating polyneuropathy, which, due to its clinical-laboratory presentation, does not include the group of "simple" neuropathies, thus requiring further examinations. Neurophysiological testing should be performed using the protocol for neuropathy examinations. Neurophysiological examination, during the electroneurographic examination, shows neurographic parameters referring to polyneuropatic demyelinating type of lesion, while the electromyographic finding records the presence of neuropathic lesions (denervation activity, great action potentials with a reduced sample). A 54-year-old patient was diagnosed to have a "complicated" demyelinating polyneuropathy according to the clinical-laboratory findings and electromyographic examination. Exclusion criteria, targeted diagnostic examinations, considering the mentioned peripheral neuropathies, pointed to acute inflammatory demyelinating polyneuropathy. However, the chronic inflammatory demyelinating polyneuropathy was finally differentiated during the clinical and electromyographic monitoring.

Demyelinating polyneuropathy with focally folded myelin sheaths in a family of Miniature Schnauzer dogs.

PubMed

Vanhaesebrouck, An E; Couturier, Jérôme; Cauzinille, Laurent; Mizisin, Andrew P; Shelton, G Diane; Granger, Nicolas

2008-12-15

A spontaneous demyelinating polyneuropathy in two young Miniature Schnauzer dogs was characterized clinically, electrophysiologically and histopathologically. Both dogs were related and a third dog, belonging to the same family, had similar clinical signs. On presentation, clinical signs were restricted to respiratory dysfunction. Electrophysiological tests showed a dramatic decrease in both motor and sensory nerve conduction velocities. Microscopic examination of peripheral nerve biopsies (light and electron microscopy, teased nerve fibers), showed that this neuropathy was characterized by segmental demyelination and focally folded myelin sheaths. Various clinical syndromes associated with tomacula or focal thickening of the myelin sheath of the peripheral nerves have been described in humans and shown to be caused by gene mutations affecting the myelin proteins, such as the hereditary neuropathy with liability to pressure palsies or the demyelinating forms of Charcot-Marie-Tooth disease. In animals, a tomaculous neuropathy has been reported in cattle and chickens but not in carnivores. Here we report a demyelinating peripheral neuropathy with tomacula in two Miniature Schnauzer dogs.

Retinal Disease in Marfan Syndrome: From the Marfan Eye Consortium of Chicago.

PubMed

Rahmani, Safa; Lyon, Alice T; Fawzi, Amani A; Maumenee, Irene H; Mets, Marilyn B

2015-10-01

To study the prevalence of peripheral retinal disease in patients with Marfan Syndrome (MFS). In this observational, cross-sectional case series, patients with MFS were recruited by the Marfan Eye Consortium of Chicago during the National Marfan Foundation's annual conference. Patients underwent a fully dilated exam by vitreoretinal specialists in addition to ultra-widefield fundus photography using a scanning laser ophthalmoscope (Optos 200Tx; Optos PLC, Dunfermline, Scotland, United Kingdom). Clinical examination revealed posterior segment pathology in 18% of eyes with increased incidence to 70% in patients with a subluxed lens. In six out of 10 subjects in whom the clinical exam was suboptimal (young age, small pupil, and limited cooperation), the Optos provided a superior view of the peripheral retina compared to clinical exam alone. Clinical exam of MFS patients revealed similar posterior segment pathology as noted in previous literature, with improved detection of peripheral retinal disease with the use of ultra-widefield imaging. Copyright 2015, SLACK Incorporated.

Atherectomy in Peripheral Artery Disease: A Review.

PubMed

Bhat, Tariq M; Afari, Maxwell E; Garcia, Lawrence A

2017-04-01

Peripheral arterial disease (PAD) is a clinical manifestation of systemic atherosclerosis and is associated with significant morbidity and mortality. The physiological force and shear stress from angioplasty and stenting have made PAD treatment challenging. Atherectomy devices have continued to emerge as a major therapy in the management of peripheral vascular disease. This article presents a review of the current literature for the atherectomy devices used in PAD.

Peripheral-specific y2 receptor knockdown protects mice from high-fat diet-induced obesity.

PubMed

Shi, Yan-Chuan; Lin, Shu; Castillo, Lesley; Aljanova, Aygul; Enriquez, Ronaldo F; Nguyen, Amy D; Baldock, Paul A; Zhang, Lei; Bijker, Martijn S; Macia, Laurence; Yulyaningsih, Ernie; Zhang, Hui; Lau, Jackie; Sainsbury, Amanda; Herzog, Herbert

2011-11-01

Y2 receptors, particularly those in the brain, have been implicated in neuropeptide Y (NPY)-mediated effects on energy homeostasis and bone mass. Recent evidence also indicates a role for Y2 receptors in peripheral tissues in this process by promoting adipose tissue accretion; however their effects on energy balance remain unclear. Here, we show that adult-onset conditional knockdown of Y2 receptors predominantly in peripheral tissues results in protection against diet-induced obesity accompanied by significantly reduced weight gain, marked reduction in adiposity and improvements in glucose tolerance without any adverse effect on lean mass or bone. These changes occur in association with significant increases in energy expenditure, respiratory exchange ratio, and physical activity and despite concurrent hyperphagia. On a chow diet, knockdown of peripheral Y2 receptors results in increased respiratory exchange ratio and physical activity with no effect on lean or bone mass, but decreases energy expenditure without effecting body weight or food intake. These results suggest that peripheral Y2 receptor signaling is critical in the regulation of oxidative fuel selection and physical activity and protects against the diet-induced obesity. The lack of effects on bone mass seen in this model further indicates that bone mass is primarily controlled by non-peripheral Y2 receptors. This study provides evidence that novel drugs that target peripheral rather than central Y2 receptors could provide benefits for the treatment of obesity and glucose intolerance without adverse effects on lean and bone mass, with the additional benefit of avoiding side effects often associated with pharmaceuticals that act on the central nervous system.

[Acute limb ischemia from the general surgeon's point of view. How much knowledge of vascular surgery is necessary?].

PubMed

Kopp, R; Weidenhagen, R; Hornung, H; Jauch, K W; Lauterjung, L

2003-12-01

The diagnosis of acute peripheral ischemia can be obtained based on clinical presentation, inspection, and palpation of the affected extremity. Unfractionated heparin as a single shot is immediately given followed by continuous infusion when diagnosis is clinically evident and contraindications are excluded. Thromboembolectomy using a Fogarty catheter is immediately performed in patients with evidence of arterial embolization and signs of advanced ischemia (TASC IIb/III) followed by intraoperative angiography. Patients with evidence of arterial thrombosis require urgent angiography followed by thrombectomy and probably subsequent endovascular or surgical interventions and vascular reconstruction. For patients with moderate ischemia (TASC IIa), initial diagnostic angiography is recommended followed by primary thrombectomy with subsequent intraoperative angiography and immediate endovascular or operative treatment of remaining vascular problems. As an alternative therapeutic option initial catheter-guided local thrombolysis can be performed in selected patients with the intention of subsequent limb revascularization or unmasking relevant vessel alterations leading to specific endovascular or surgically performed vascular reconstruction. Possible development of muscle ischemia because of increased compartment pressure should be considered and fasciotomy performed when indicated. Primary amputation of the severely ischemic limb after initial thrombectomy might be recommended in patients with life-threatening organ failure related to muscle necrosis.

[The clinical investigation of peripheral retinal changes of anterior uveitis].

PubMed

Guo, Chunying; Qiao, Lijun; Yang, Liu

2015-10-01

To observe the peripheral retinal changes of anterior uveitis patients using ultra-wide field fluorescein angiography. Retrospective case series study. Thirty-three eyes of 20 patients diagnosed as anterior uveitis from September to November 2013 in the ophthalmic clinic of Peking University First Hospital was included. All the patients underwent routine ocular examination, followed by ultra-wide field Fluorescein. There were 13 male patients and 7 female patients, aged 23-66, an average of 46 years old. The anterior uveitis recurrent in both eyes in 13 patients and only one eye in 7 patients. Uveitis duration ranging from months to 30 years. Twenty eyes were at the active stage of the anterior uveitis while 13 eyes in the quiescent stage. Peripheral retinal vessels leakage was detected in 57.6% (19/33) of the eyes, among which in eyes with active disease the rate of peripheral retinal vessels leakage was 75% (15/20), and in eyes with quiescent disease the rate was 30.8% (4/13). Optic disk hyperfluorescence was found in 6 of 20 eyes with active disease. Cystoid macular edema was found in 4 eyes. In addition, peripheral retinal hyperfluorescence dot and zone were detected in 2 eyes. Peripheral retinal vessels were detected to have inflammative leakage in patients of anterior uveitis by ultra-wide field fluorescein agiography. Peripheral retinal inflammation may still exist even in the quiescent stage of the anterior uveitis.

Complementary therapies for peripheral arterial disease: systematic review.

PubMed

Pittler, Max H; Ernst, Edzard

2005-07-01

While peripheral arterial disease (PAD) affects a considerable proportion of patients in the primary care setting, there is a high level of use of complementary treatment options. The aim was to assess the effectiveness of any type of complementary therapy for peripheral arterial disease. A systematic review was performed. Literature searches were conducted on Medline, Embase, Amed, and the Cochrane Library until December 2004. Hand-searches of medical journals and bibliographies were conducted. There were no restrictions regarding the language of publication. The screening of studies, selection, data extraction, the assessment of methodologic quality and validation were performed independently by the two reviewers. Data from randomized controlled trials, and systematic reviews and meta-analyses, which based their findings on the results of randomized controlled trials were included. Seven systematic reviews and meta-analyses and three additional randomized controlled trials met the inclusion criteria and were reviewed. The evidence relates to acupuncture, biofeedback, chelation therapy, CO(2)-applications and the dietary supplements Allium sativum (garlic), Ginkgo biloba (ginkgo), omega-3 fatty acids, padma 28 and Vitamin E. Most studies included only patients with peripheral arterial disease in Fontaine stage II (intermittent claudication). The reviewed RCTs, systematic reviews and meta-analyses which based their findings on the results of RCTs suggest that G. biloba is effective compared with placebo for patients with intermittent claudication. Evidence also suggests that padma 28 is effective for intermittent claudication, although more data are required to confirm these findings. For all other complementary treatment options there is no evidence beyond reasonable doubt to suggest effectiveness for patients with peripheral arterial disease.

An exploratory study of temporal integration in the peripheral retina of myopes

NASA Astrophysics Data System (ADS)

Macedo, Antonio F.; Encarnação, Tito J.; Vilarinho, Daniel; Baptista, António M. G.

2017-08-01

The visual system takes time to respond to visual stimuli, neurons need to accumulate information over a time span in order to fire. Visual information perceived by the peripheral retina might be impaired by imperfect peripheral optics leading to myopia development. This study explored the effect of eccentricity, moderate myopia and peripheral refraction in temporal visual integration. Myopes and emmetropes showed similar performance at detecting briefly flashed stimuli in different retinal locations. Our results show evidence that moderate myopes have normal visual integration when refractive errors are corrected with contact lens; however, the tendency to increased temporal integration thresholds observed in myopes deserves further investigation.

The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of ixabepilone: a first in class epothilone B analogue in late-phase clinical development.

PubMed

Goel, Sanjay; Cohen, Marvin; Cömezoglu, S Nilgün; Perrin, Lionel; André, François; Jayabalan, David; Iacono, Lisa; Comprelli, Adriana; Ly, Van T; Zhang, Donglu; Xu, Carrie; Humphreys, W Griffith; McDaid, Hayley; Goldberg, Gary; Horwitz, Susan B; Mani, Sridhar

2008-05-01

To determine if ixabepilone is a substrate for cytochrome P450 3A4 (CYP3A4) and if its metabolism by this cytochrome is clinically important, we did a clinical drug interaction study in humans using ketoconazole as an inhibitor of CYP3A4. Human microsomes were used to determine the cytochrome P450 enzyme(s) involved in the metabolism of ixabepilone. Computational docking (CYP3A4) studies were done for epothilone B and ixabepilone. A follow-up clinical study was done in patients with cancer to determine if 400 mg/d ketoconazole (inhibitor of CYP3A4) altered the pharmacokinetics, drug-target interactions, and pharmacodynamics of ixabepilone. Molecular modeling and human microsomal studies predicted ixabepilone to be a good substrate for CYP3A4. In patients, ketoconazole coadministration resulted in a maximum ixabepilone dose administration to 25 mg/m(2) when compared with single-agent therapy of 40 mg/m(2). Coadministration of ketoconazole with ixabepilone resulted in a 79% increase in AUC(0-infinity). The relationship of microtubule bundle formation in peripheral blood mononuclear cells to plasma ixabepilone concentration was well described by the Hill equation. Microtubule bundle formation in peripheral blood mononuclear cells correlated with neutropenia. Ixabepilone is a good CYP3A4 substrate in vitro; however, in humans, it is likely to be cleared by multiple mechanisms. Furthermore, our results provide evidence that there is a direct relationship between ixabepilone pharmacokinetics, neutrophil counts, and microtubule bundle formation in PBMCs. Strong inhibitors of CYP3A4 should be used cautiously in the context of ixabepilone dosing.

Immune checkpoint inhibitor-related myocarditis.

PubMed

Tajiri, Kazuko; Aonuma, Kazutaka; Sekine, Ikuo

2018-01-01

Immune checkpoint inhibitors have demonstrated significant clinical benefit in many cancers. The clinical benefit afforded by these treatments can be accompanied by a unique and distinct spectrum of adverse events. Recently, several fatal cases of immune checkpoint inhibitor-related myocarditis were reported. Although its frequency is comparatively lower than that of other immune-related adverse events, myocarditis can lead to circulatory collapse and lethal ventricular arrhythmia. Immune checkpoints, cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), play important roles in establishing peripheral tolerance to the heart. Evidence from studies using genetically engineered mouse models suggests that CTLA-4 signaling terminates proliferation and promotes anergy during the primary response to cardiac self-peptide recognition. PD-1 signaling restrains autoreactive T cells that enter the peripheral tissues and recognize cardiac-peptide, maintaining them in an anergic state. Patients affected by immune checkpoint inhibitor-related myocarditis often experience rapid onset of profound hemodynamic compromise progressing to cardiogenic shock. Early diagnosis is mandatory to address specific therapy and correct the timing of circulatory support. However, the diagnosis of myocarditis is challenging due to the heterogeneity of clinical presentations. Owing to its early onset, nonspecific symptomatology and fulminant progression, especially when these drugs are used in combination, oncologists should be vigilant for immune checkpoint inhibitor-related myocarditis. With many questions yet to be answered, from basic immune biology to clinical management, future research should aim to optimize the use of these drugs by identifying predictive biomarkers of either a response to therapy or the risks of myocarditis development. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Atherectomy for peripheral arterial disease].

PubMed

Londero, Louise Skovgaard; Høgh, Annette Langager; Lindholt, Jes Sanddal

2015-04-13

Symptomatic peripheral arterial disease is managed according to national and international guidelines and the number of vascular reconstructions performed each year has increased over the past decade mainly due to an increasing frequency of endovascular procedures. Atherectomy as an alternative to the established treatment of symptomatic peripheral arterial disease has recently been analysed in a Cochrane review. In Denmark, atherectomy is not performed and so far the evidence is poor as the method is not an alternative to the established treatment in this country.

Imaging of the peripheral retina

PubMed Central

Kernt, Marcus; Kampik, Anselm

2013-01-01

The technical progress of the recent years has revolutionized imaging in ophthalmology. Scanning laser ophthalmoscopy (SLO), digital angiography, optical coherence tomography (OCT), and detection of fundus autofluorescence (FAF) have fundamentally changed our understanding of numerous retinal and choroidal diseases. Besides the tremendous advances in macular diagnostics, there is more and more evidence that central pathologies are often directly linked to changes in the peripheral retina. This review provides a brief overview on current posterior segment imaging techniques with a special focus on the peripheral retina. PMID:24391370

The Place of Nailfold Capillaroscopy Among Instrumental Methods for Assessment of Some Peripheral Ischaemic Syndromes in Rheumatology.

PubMed

Lambova, Sevdalina N

2016-01-01

Micro- and macrovascular pathology is a frequent finding in a number of common rheumatic diseases. Secondary Raynaud's phenomenon (RP) is among the most common symptoms in systemic sclerosis and several other systemic autoimmune diseases including a broad differential diagnosis. It should be also differential from other peripheral vascular syndromes such as embolism, thrombosis, etc., some of which lead to clinical manifestation of the blue toe syndrome. The current review discusses the instrumental methods for vascular assessments. Nailfold capillaroscopy is the only method among the imaging techniques that can be used for morphological assessment of the nutritive capillaries in the nailfold area. Laser-Doppler flowmetry and laser-Doppler imaging are methods for functional assessment of microcirculation, while thermography and plethysmography reflect both blood flow in peripheral arteries and microcirculation. Doppler ultrasound and angiography visualize peripheral arteries. The choice of the appropriate instrumental method is guided by the clinical presentation. The main role of capillaroscopy is to provide differential diagnosis between primary and secondary RP. In rheumatology, capillaroscopic changes in systemic sclerosis have been recently defined as diagnostic. The appearance of abnormal capillaroscopic pattern inherits high positive predictive value for the development of a connective tissue disease that is higher than the predictive value of antinuclear antibodies. In cases of abrupt onset of peripheral ischaemia, clinical signs of critical ischaemia, unilateral or lower limb involvement, Doppler ultrasound and angiography are indicated. The most common causes for such clinical picture that may be referred to rheumatologic consultation are the antiphospholipid syndrome, mimickers of vasculitides such as atherosclerosis with cholesterol emboli, and neoplasms.

Innate immune receptor Toll-like receptor 4 signalling in neuropsychiatric diseases.

PubMed

García Bueno, B; Caso, J R; Madrigal, J L M; Leza, J C

2016-05-01

The innate immunity is a stereotyped first line of defense against pathogens and unspecified damage signals. One of main actors of innate immunity are the Toll-like receptors (TLRs), and one of the better characterized members of this family is TLR-4, that it is mainly activated by Gram-negative bacteria lipopolysaccharide. In brain, TLR-4 organizes innate immune responses against infections or cellular damage, but also possesses other physiological functions. In the last years, some evidences suggest a role of TLR-4 in stress and stress-related neuropsychiatric diseases. Peripheral and brain TLR-4 activation triggers sickness behavior, and its expression is a risk factor of depression. Some elements of the TLR-4 signaling pathway are up-regulated in peripheral samples and brain post-mortem tissue from depressed and suicidal patients. The "leaky gut" hypothesis of neuropsychiatric diseases is based on the existence of an increase of the intestinal permeability which results in bacterial translocation able to activate TLR-4. Enhanced peripheral TLR-4 expression/activity has been described in subjects diagnosed with schizophrenia, bipolar disorder and in autistic children. A role for TLR-4 in drugs abuse has been also proposed. The therapeutic potential of pharmacological/genetic modulation of TLRs signaling pathways in neuropsychiatry is promising, but a great preclinical/clinical scientific effort is still needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tamoxifen induces apoptotic neutrophil efferocytosis in horses.

PubMed

Olave, C; Morales, N; Uberti, B; Henriquez, C; Sarmiento, J; Ortloff, A; Folch, H; Moran, G

2018-03-01

Macrophages and neutrophils are important cellular components in the process of acute inflammation and its subsequent resolution, and evidence increasingly suggests that they play important functions during the resolution of chronic, adaptive inflammatory processes. Exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including allergic asthma and chronic obstructive pulmonary disease in humans, and equine asthma (also known as recurrent airway obstruction (RAO). Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effects on cell growth and survival. Previous studies showed that TX treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and BALF neutrophils, reduction of BALF neutrophils, and improvement in animals' clinical status. The aim of this study was to describe if TX induces in vitro efferocytosis of neutrophils by alveolar macrophages. Efferocytosis assay, myeloperoxidase (MPO) detection and translocation phosphatidylserine (PS) were performed on neutrophils isolated from peripheral blood samples from five healthy horses. In in vitro samples from heathy horses, TX treatment increases the phenomenon of efferocytosis of peripheral neutrophils by alveolar macrophages. Similar increases in supernatant MPO concentration and PS translocation were observed in TX-treated neutrophils, compared to control cells. In conclusion, these results confirm that tamoxifen has a direct effect on equine peripheral blood neutrophils, through stimulation of the engulfment of apoptotic neutrophils by alveolar macrophages.

Genetics Home Reference: hereditary sensory and autonomic neuropathy type V

MedlinePlus

... links) National Institute of Neurological Disorders and Stroke: Peripheral Neuropathy National Institutes of Health Rare Diseases Clinical Research ... neuropathy type 5 University of Chicago Center for Peripheral Neuropathy Patient Support and Advocacy Resources (1 link) The ...

Clinical Remission of Sight-Threatening Non-Infectious Uveitis Is Characterized by an Upregulation of Peripheral T-Regulatory Cell Polarized Towards T-bet and TIGIT.

PubMed

Gilbert, Rose M; Zhang, Xiaozhe; Sampson, Robert D; Ehrenstein, Michael R; Nguyen, Dao X; Chaudhry, Mahid; Mein, Charles; Mahmud, Nadiya; Galatowicz, Grazyna; Tomkins-Netzer, Oren; Calder, Virginia L; Lightman, Sue

2018-01-01

Non-infectious uveitis can cause chronic relapsing and remitting ocular inflammation, which may require high dose systemic immunosuppression to prevent severe sight loss. It has been classically described as an autoimmune disease, mediated by pro-inflammatory Th1 and Th17 T-cell subsets. Studies suggest that natural immunosuppressive CD4 + CD25 + FoxP3 + T-regulatory cells (Tregs) are involved in resolution of inflammation and may be involved in the maintenance of clinical remission. To investigate whether there is a peripheral blood immunoregulatory phenotype associated with clinical remission of sight-threatening non-infectious uveitis by comparing peripheral blood levels of Treg, Th1, and Th17, and associated DNA methylation and cytokine levels in patients with active uveitic disease, control subjects and patients (with previously active disease) in clinical remission induced by immunosuppressive drugs. Isolated peripheral blood mononuclear cells (PBMC) from peripheral blood samples from prospectively recruited subjects were analyzed by flow cytometry for CD3, CD4, FoxP3, TIGIT, T-bet, and related orphan receptor γt. Epigenetic DNA methylation levels of FOXP3 Treg-specific demethylated region (TSDR), FOXP3 promoter, TBX21, RORC2, and TIGIT loci were determined in cryopreserved PBMC using a next-generation sequencing approach. Related cytokines were measured in blood sera. Functional suppressive capacity of Treg was assessed using T-cell proliferation assays. Fifty patients with uveitis (intermediate, posterior, and panuveitis) and 10 control subjects were recruited. The frequency of CD4 + CD25 + FoxP3 + Treg, TIGIT + Treg, and T-bet + Treg and the ratio of Treg to Th1 were significantly higher in remission patients compared with patients with active uveitic disease; and TIGIT + Tregs were a significant predictor of clinical remission. Treg from patients in clinical remission demonstrated a high level of in vitro suppressive function compared with Treg from control subjects and from patients with untreated active disease. PBMC from patients in clinical remission had significantly lower methylation levels at the FOXP3 TSDR, FOXP3 promoter, and TIGIT loci and higher levels at RORC loci than those with active disease. Clinical remission was also associated with significantly higher serum levels of transforming growth factor β and IL-10, which positively correlated with Treg levels, and lower serum levels of IFNγ, IL-17A, and IL-22 compared with patients with active disease. Clinical remission of sight-threatening non-infectious uveitis has an immunoregulatory phenotype characterized by upregulation of peripheral Treg, polarized toward T-bet and TIGIT. These findings may assist with individualized therapy of uveitis, by informing whether drug therapy has induced phenotypically stable Treg associated with long-term clinical remission.

The Prevalence and Regional Variation of Major Depressive Disorder Among Patients With Peripheral Arterial Disease in the Medicare Population.

PubMed

Columbo, Jesse A; Stone, David H; Goodney, Philip P; Nolan, Brian W; Stableford, Jennifer A; Brooke, Benjamin S; Powell, Richard J; Finn, Christine T

2016-05-01

Current evidence suggests an association between coronary artery disease and major depressive disorder (MDD). Data to support a similar association between peripheral arterial disease (PAD) and MDD are more limited. This study examines the prevalence and regional variation of both PAD and MDD in a large contemporary patient sample. All Medicare claims, part A and B, from January 2009 until December 2011 were queried using diagnosis codes specific for a previously validated clinical algorithm for PAD and major depression. Codes for PAD included those specific to cerebrovascular disease, abdominal aortic aneurysm, and peripheral vascular disease. Peripheral arterial disease prevalence, major depression prevalence, and coprevalence rates were determined, respectively. Regional variation of both conditions was determined using zip code data to identify potential endemic areas of disease intensity for both diagnoses. Over the study interval, the percentage of Medicare beneficiaries with a diagnosis of PAD remained relatively constant (3.0%-3.7%, n = 0.85-1.06 million in part A and 17.4%-17.5%, n = 4.82-4.93 million in part B), and MDD showed a similar trend (1.6%-2.7%, n = 0.46-0.79 million in part A and 6.1%-6.7%, n = 1.69-1.90 million in part B). The observed rate of MDD in those with an established diagnosis of PAD was 5-fold higher than those without PAD in part A claims (1.8-fold in part B claims). Moreover, there was a significant linear geographic correlation among patients with PAD and MDD (r = .54, P ≤ .01). This study documents a correlation between PAD and MDD and may, therefore, identify an at-risk population susceptible to inferior clinical outcomes. Significant regional variation exists in the prevalence of PAD and MDD, though there appear to be specific endemic regions notable for both disorders. Accordingly, health-care resource allocation toward endemic regions may help improve population health among this at-risk cohort. © The Author(s) 2016.

Immunomodulatory Effects Mediated by Dopamine

PubMed Central

Alvarez-Herrera, Samantha; Pérez-Sánchez, Gilberto; Becerril-Villanueva, Enrique; Cruz-Fuentes, Carlos; Flores-Gutierrez, Enrique Octavio; Quintero-Fabián, Saray

2016-01-01

Dopamine (DA), a neurotransmitter in the central nervous system (CNS), has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS) that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R) and D2-like receptors (D2R, D3R, and D4R). The expression of these components depends on the state of cellular activation and the concentration and time of exposure to DA. Receptors that are expressed in leukocytes are linked to signaling pathways that are mediated by changes in cAMP concentration, which in turn triggers changes in phenotype and cellular function. According to the leukocyte lineage, the effects of DA are associated with such processes as respiratory burst, cytokine and antibody secretion, chemotaxis, apoptosis, and cytotoxicity. In clinical conditions such as schizophrenia, Parkinson disease, Tourette syndrome, and multiple sclerosis (MS), there are evident alterations during immune responses in leukocytes, in which changes in DA receptor density have been observed. Several groups have proposed that these findings are useful in establishing clinical status and clinical markers. PMID:27795960

Curcumin and Resveratrol in the Management of Cognitive Disorders: What is the Clinical Evidence?

PubMed

Mazzanti, Gabriela; Di Giacomo, Silvia

2016-09-17

A growing body of in vitro and in vivo evidences shows a possible role of polyphenols in counteracting neurodegeneration: curcumin and resveratrol are attractive substances in this regard. In fact, epidemiological studies highlight a neuroprotective effect of turmeric (rhizome of Curcuma longa L.), the main source of curcumin. Moreover, the consumption of red wine, the main source of resveratrol, has been related to a lower risk of developing dementia. In this review, we analyzed the published clinical trials investigating curcumin and resveratrol in the prevention or treatment of cognitive disorders. The ongoing studies were also described, in order to give an overview of the current search on this topic. The results of published trials (five for curcumin, six for resveratrol) are disappointing and do not allow to draw conclusions about the therapeutic or neuroprotective potential of curcumin and resveratrol. These compounds, being capable of interfering with several processes implicated in the early stages of dementia, could be useful in preventing or in slowing down the pathology. To this aim, an early diagnosis using peripheral biomarkers becomes necessary. Furthermore, the potential preventive activity of curcumin and resveratrol should be evaluated in long-term exposure clinical trials, using preparations with high bioavailability and that are well standardized.

The Functional and Clinical Significance of the 24-Hour Rhythm of Circulating Glucocorticoids

PubMed Central

Oster, Henrik; Challet, Etienne; Ott, Volker; Arvat, Emanuela; de Kloet, E. Ronald; Dijk, Derk-Jan; Lightman, Stafford; Vgontzas, Alexandros

2017-01-01

Adrenal glucocorticoids are major modulators of multiple functions, including energy metabolism, stress responses, immunity, and cognition. The endogenous secretion of glucocorticoids is normally characterized by a prominent and robust circadian (around 24 hours) oscillation, with a daily peak around the time of the habitual sleep-wake transition and minimal levels in the evening and early part of the night. It has long been recognized that this 24-hour rhythm partly reflects the activity of a master circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus. In the past decade, secondary circadian clocks based on the same molecular machinery as the central master pacemaker were found in other brain areas as well as in most peripheral tissues, including the adrenal glands. Evidence is rapidly accumulating to indicate that misalignment between central and peripheral clocks has a host of adverse effects. The robust rhythm in circulating glucocorticoid levels has been recognized as a major internal synchronizer of the circadian system. The present review examines the scientific foundation of these novel advances and their implications for health and disease prevention and treatment. PMID:27749086

Mind and body: how the health of the body impacts on neuropsychiatry

PubMed Central

Renoir, Thibault; Hasebe, Kyoko; Gray, Laura

2013-01-01

It has long been established in traditional forms of medicine and in anecdotal knowledge that the health of the body and the mind are inextricably linked. Strong and continually developing evidence now suggests a link between disorders which involve Hypothalamic-Pituitary-Adrenal axis (HPA) dysregulation and the risk of developing psychiatric disease. For instance, adverse or excessive responses to stressful experiences are built into the diagnostic criteria for several psychiatric disorders, including depression and anxiety disorders. Interestingly, peripheral disorders such as metabolic disorders and cardiovascular diseases are also associated with HPA changes. Furthermore, many other systemic disorders associated with a higher incidence of psychiatric disease involve a significant inflammatory component. In fact, inflammatory and endocrine pathways seem to interact in both the periphery and the central nervous system (CNS) to potentiate states of psychiatric dysfunction. This review synthesizes clinical and animal data looking at interactions between peripheral and central factors, developing an understanding at the molecular and cellular level of how processes in the entire body can impact on mental state and psychiatric health. PMID:24385966

Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis.

PubMed

Jenkins, Trisha A; Nguyen, Jason C D; Polglaze, Kate E; Bertrand, Paul P

2016-01-20

The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. Manipulation of tryptophan levels, acutely or chronically, by depletion or supplementation, is an experimental procedure for modifying peripheral and central serotonin levels. These studies have allowed us to establish the role of serotonin in higher order brain function in both preclinical and clinical situations and have precipitated the finding that low brain serotonin levels are associated with poor memory and depressed mood. The gut-brain axis is a bi-directional system between the brain and gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. An influence of gut microbiota on behaviour is becoming increasingly evident, as is the extension to tryptophan and serotonin, producing a possibility that alterations in the gut may be important in the pathophysiology of human central nervous system disorders. In this review we will discuss the effect of manipulating tryptophan on mood and cognition, and discuss a possible influence of the gut-brain axis.

Clinical implications of basic science discoveries: nociceptive neurons as targets to control immunity--potential relevance for transplantation.

PubMed

Larregina, A T; Divito, S J; Morelli, A E

2015-06-01

Increasing evidence indicates the existence of a complex cross-regulation between the most important biosensors of the human body: The immune and nervous systems. Cytokines control body temperature and trigger autoimmune disorders in the central nervous system, whereas neuropeptides released in peripheral tissues and lymphoid organs modulate inflammatory (innate) and adaptive immune responses. Surprisingly, the effects of nerve fibers and the antidromic release of its pro-inflammatory neuropeptides on the leukocytes of the immune system that mediate graft rejection are practically unknown. In the transplantation field, such area of research remains practically unexplored. A recent study by Riol-Blanco et al has revealed new details on how nociceptive nerves regulate the pro-inflammatory function of leukocytes in peripheral tissues. Although the mechanism(s) by which neuroinflammation affects the immune response against the allograft remains unknown, recent data suggest that this new area of research is worth exploring for potential development of novel complementary therapies for prevention/treatment of graft rejection. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Central attention is serial but mid-level and peripheral attention are parallel—a hypothesis

PubMed Central

Marois, Rene

2016-01-01

In this brief review, we will argue that attention falls along a hierarchy from peripheral through central mechanisms. We further argue that these mechanisms are distinguished not just by their functional roles in cognition, but also by a distinction between serial mechanisms (associated with central attention) and parallel mechanisms (associated with mid-level and peripheral attention). In particular, we suggest that peripheral attentional deployments in distinct representational systems may be maintained simultaneously with little or no interference, but that the serial nature of central attention means that even tasks that largely rely on distinct representational systems will come into conflict when central attention is demanded. We go on to review both behavioral and neural evidence for this prediction. We conclude that even though the existing evidence mostly favors our account of serial central and parallel non-central attention, we know of no experiment that has conclusively borne out these claims. As such, this paper offers a framework of attentional mechanisms that will aid in guiding future research on this topic. PMID:27388496

Mechanisms and Management of Diabetic Painful Distal Symmetrical Polyneuropathy

PubMed Central

Tesfaye, Solomon; Boulton, Andrew J.M.; Dickenson, Anthony H.

2013-01-01

Although a number of the diabetic neuropathies may result in painful symptomatology, this review focuses on the most common: chronic sensorimotor distal symmetrical polyneuropathy (DSPN). It is estimated that 15–20% of diabetic patients may have painful DSPN, but not all of these will require therapy. In practice, the diagnosis of DSPN is a clinical one, whereas for longitudinal studies and clinical trials, quantitative sensory testing and electrophysiological assessment are usually necessary. A number of simple numeric rating scales are available to assess the frequency and severity of neuropathic pain. Although the exact pathophysiological processes that result in diabetic neuropathic pain remain enigmatic, both peripheral and central mechanisms have been implicated, and extend from altered channel function in peripheral nerve through enhanced spinal processing and changes in many higher centers. A number of pharmacological agents have proven efficacy in painful DSPN, but all are prone to side effects, and none impact the underlying pathophysiological abnormalities because they are only symptomatic therapy. The two first-line therapies approved by regulatory authorities for painful neuropathy are duloxetine and pregabalin. α-Lipoic acid, an antioxidant and pathogenic therapy, has evidence of efficacy but is not licensed in the U.S. and several European countries. All patients with DSPN are at increased risk of foot ulceration and require foot care, education, and if possible, regular podiatry assessment. PMID:23970715

Incidence of reactive hyperplastic lesions in the oral cavity: a 10 year retrospective study in Santa Catarina, Brazil.

PubMed

Dutra, Kamile Leonardi; Longo, Lunardo; Grando, Liliane Janete; Rivero, Elena Riet Correa

2018-04-17

Reactive hyperplastic lesions develop in response to a chronic injury simulating an exuberant tissue repair response. They represent some of the most common oral lesions including inflammatory fibrous hyperplasia, oral pyogenic granuloma, giant cell fibroma, peripheral ossifying fibroma, and peripheral giant cell lesions. The incidence of those lesions was investigated in an oral pathology service, and the clinical characteristics, associated etiological factors, concordance between the clinical and histopathological diagnostic was determined. A total of 2400 patient records were screened from 2006 to 2016. Clinical features were recorded from biopsy reports and patients' files. A total of 534 cases of reactive hyperplastic lesions were retrieved and retrospectively studied, representing 22.25% of all diagnoses. The most frequent lesion was inflammatory fibrous hyperplasia (72.09%), followed by oral pyogenic granuloma (11.79%), giant cell fibroma (7.30%), peripheral ossifying fibroma (5.24%), and peripheral giant cell lesions (3.55%). Females were predominantly affected (74.19%), the gingiva and alveolar ridge were the predominant anatomical site (32.89%), and chronic traumatism was presented as the main etiological factor. The age widely ranges from the 1st decade of life to the 7th. Clinically, the reactive hyperplastic lesions consisted of small lesions (0.5-2cm) and shared a strong likeness in color to the oral mucosa. The concordance between the clinical and histopathological diagnostic was high (82.5%). Reactive hyperplastic lesions had a high incidence among oral pathologies. The understanding of their clinical features helps to achieve a clearer clinical and etiological diagnosis, and the knowledge of factors related to their development. This may contribute to adequate treatment and positive prognosis. Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Clinical observation of the application of autologous peripheral blood stem cell transplantation for the treatment of diabetic foot gangrene

PubMed Central

XU, SHI-MIN; LIANG, TING

2016-01-01

The aim of the present study was to investigate the optimal mobilization plan in autologous peripheral blood stem cell transplantation for the treatment of diabetic foot and to observe its clinical curative effect. A total of 127 patients with diabetic foot were treated with different doses of granulocyte colony stimulating factor (G-CSF) to mobilize their hematopoietic stem cells. Subsequently, the extracted stem cell suspension was injected into the ischemic lower extremities along the blood vessels in the areas presenting with pathological changes. Following the treatment, the intermittent claudication distance, skin temperature, ankle brachial index and pain scores of the patients were evaluated. In addition, the associations among the mobilization time, doses and peripheral blood CD34+ level were analyzed. The collection efficiency of the stem cells was associated with the dose of G-CSF and the mobilization time. Following the injection of the autologous peripheral blood stem cell suspension, the ischemic area of the patients was improved significantly. In conclusion, autologous peripheral blood stem cell transplantation can promote the establishment of collateral circulation in patients with diabetic foot, and the optimal time for gathering stem cells is closely correlated with the peripheral blood CD34+ level. PMID:26889255

Recovery of Peripheral Nerve with Massive Loss Defect by Tissue Engineered Guiding Regenerative Gel

PubMed Central

Nevo, Zvi

2014-01-01

Objective. Guiding Regeneration Gel (GRG) was developed in response to the clinical need of improving treatment for peripheral nerve injuries and helping patients regenerate massive regional losses in peripheral nerves. The efficacy of GRG based on tissue engineering technology for the treatment of complete peripheral nerve injury with significant loss defect was investigated. Background. Many severe peripheral nerve injuries can only be treated through surgical reconstructive procedures. Such procedures are challenging, since functional recovery is slow and can be unsatisfactory. One of the most promising solutions already in clinical practice is synthetic nerve conduits connecting the ends of damaged nerve supporting nerve regeneration. However, this solution still does not enable recovery of massive nerve loss defect. The proposed technology is a biocompatible and biodegradable gel enhancing axonal growth and nerve regeneration. It is composed of a complex of substances comprising transparent, highly viscous gel resembling the extracellular matrix that is almost impermeable to liquids and gasses, flexible, elastic, malleable, and adaptable to various shapes and formats. Preclinical study on rat model of peripheral nerve injury showed that GRG enhanced nerve regeneration when placed in nerve conduits, enabling recovery of massive nerve loss, previously unbridgeable, and enabled nerve regeneration at least as good as with autologous nerve graft “gold standard” treatment. PMID:25105121

STELLATE NONHEREDITARY IDIOPATHIC FOVEOMACULAR RETINOSCHISIS ACCOMPANIED BY CONTRALATERAL PERIPHERAL RETINOSCHISIS.

PubMed

Ahmed, Daniel; Stattin, Martin; Glittenberg, Carl; Krebs, Ilse; Ansari-Shahrezaei, Siamak

2017-01-16

To present a patient with stellate nonhereditary idiopathic foveomacular retinoschisis on one eye and peripheral retinoschisis without foveal affection on the other eye. A case report with complete workup of family history and clinical examination, including multimodal imaging with optical coherence tomography and angiography, fluorescein angiography, and infrared fundus imaging. Genetic testing for gene mutation XRLS1 was performed. A white woman with unremarkable medical history presented with stellate foveal splitting of the outer plexiform layer on the right eye and peripheral splitting of the outer plexiform layer on both eyes. All known allegeable trigger factors for the existence of a hereditary or acquired foveomacular retinoschisis were ruled out either by clinical presentation or genetic testing. This led to the diagnosis of stellate nonhereditary idiopathic foveomacular retinoschisis with central involvement only present on one eye. Although peripheral schisis of the outer plexiform layer is often concomitant with central splitting in X-linked juvenile retinoschisis, this is the first known report of nonhereditary cleavage of the outer plexiform layer of the peripheral retina without central affection in a patient with documented stellate nonhereditary idiopathic foveomacular retinoschisis on the other eye. These findings suggest an accurate bilateral examination of the peripheral retina while confirming the diagnose of stellate nonhereditary idiopathic foveomacular retinoschisis.

Optimizing Parkinson's disease diagnosis: the role of a dual nuclear imaging algorithm.

PubMed

Langston, J William; Wiley, Jesse C; Tagliati, Michele

2018-01-01

The diagnosis of Parkinson's disease (PD) currently relies almost exclusively on the clinical judgment of an experienced neurologist, ideally a specialist in movement disorders. However, such clinical diagnosis is often incorrect in a large percentage of patients, particularly in the early stages of the disease. A commercially available, objective and quantitative marker of nigrostriatal neurodegeneration was recently provided by 123-iodine 123 I-ioflupane SPECT imaging, which is however unable to differentiate PD from a variety of other parkinsonian syndromes associated with striatal dopamine deficiency. There is evidence to support an algorithm utilizing a dual neuroimaging strategy combining 123 I-ioflupane SPECT and the noradrenergic receptor ligand 123 I-metaiodobenzylguanidine (MIBG), which assesses the post-ganglion peripheral autonomic nervous system. Evolving concepts regarding the synucleinopathy affecting the central and peripheral autonomic nervous systems as part of a multisystem disease are reviewed to sustain such strategy. Data are presented to show how MIBG deficits are a common feature of multisystem Lewy body disease and can be used as a unique feature to distinguish PD from atypical parkinsonisms. We propose that the combination of cardiac (MIBG) and cerebral 123 I-ioflupane SPECT could satisfy one of the most significant unmet needs of current PD diagnosis and management, namely the early and accurate diagnosis of patients with typical Lewy body PD. Exemplary case scenarios will be described, highlighting how dual neuroimaging strategy can maximize diagnostic accuracy for patient care, clinical trials, pre-symptomatic PD screening, and special cases provided by specific genetic mutations associated with PD.

Treating Diabetic Neuropathy: Present Strategies and Emerging Solutions

PubMed Central

Javed, Saad; Alam, Uazman; Malik, Rayaz A.

2015-01-01

Diabetic peripheral neuropathies (DPN) are a heterogeneous group of disorders caused by neuronal dysfunction in patients with diabetes. They have differing clinical courses, distributions, fiber involvement (large or small), and pathophysiology. These complications are associated with increased morbidity, distress, and healthcare costs. Approximately 50% of patients with diabetes develop peripheral neuropathy, and the projected rise in the global burden of diabetes is spurring an increase in neuropathy. Distal symmetrical polyneuropathy (DSPN) with painful diabetic neuropathy, occurring in around 20% of diabetes patients, and diabetic autonomic neuropathy (DAN) are the most common manifestations of DPN. Optimal glucose control represents the only broadly accepted therapeutic option though evidence of its benefit in type 2 diabetes is unclear. A number of symptomatic treatments are recommended in clinical guidelines for the management of painful DPN, including antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids, and topical agents such as capsaicin. However, monotherapy is frequently not effective in achieving complete resolution of pain in DPN. There is a growing need for head-to-head studies of different single-drug and combination pharmacotherapies. Due to the ubiquity of autonomic innervation in the body, DAN causes a plethora of symptoms and signs affecting cardiovascular, urogenital, gastrointestinal, pupillomotor, thermoregulatory, and sudomotor systems. The current treatment of DAN is largely symptomatic, and does not correct the underlying autonomic nerve deficit. A number of novel potential candidates, including erythropoietin analogues, angiotensin II receptor type 2 antagonists, and sodium channel blockers are currently being evaluated in phase II clinical trials. PMID:26676662

Effectiveness of Transcutaneous Electrical Nerve Stimulation for Treatment of Hyperalgesia and Pain

PubMed Central

DeSantana, Josimari M.; Walsh, Deirdre M.; Vance, Carol; Rakel, Barbara A.; Sluka, Kathleen A.

2009-01-01

Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacologic treatment for pain relief. TENS has been used to treat a variety of painful conditions. This review updates the basic and clinical science regarding the use of TENS that has been published in the past 3 years (ie, 2005−2008). Basic science studies using animal models of inflammation show changes in the peripheral nervous system, as well as in the spinal cord and descending inhibitory pathways, in response to TENS. Translational studies show mechanisms to prevent analgesic tolerance to repeated application of TENS. This review also highlights data from recent randomized, placebo-controlled trials and current systematic reviews. Clinical trials suggest that adequate dosing, particularly intensity, is critical to obtaining pain relief with TENS. Thus, evidence continues to emerge from both basic science and clinical trials supporting the use of TENS for the treatment of a variety of painful conditions while identifying strategies to increase TENS effectiveness. PMID:19007541

Neuropsychiatric Systemic Lupus Erythematosus Involvement: Towards a Tailored Approach to Our Patients?

PubMed Central

Faria, Raquel; Gonçalves, João; Dias, Rita

2017-01-01

Neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) is a complex condition that remains poorly understood, and includes heterogeneous manifestations involving both the central and peripheral nervous system, with disabling effects. There are several models to improve NPSLE diagnosis when a neurological syndrome is present. In the last couple of years, the growing knowledge of the role of cytokines and antibodies in NPSLE, as well as the development of new functional imaging techniques, has brought some insights into the physiopathology of the disease, but their validation for clinical use remains undetermined. Furthermore, besides the classic clinical approach, a new tool for screening the 19 NPSLE syndromes has also been developed. Regarding NPSLE therapeutics, there is still no evidence-based treatment approach, but some data support the safety of biological medication when classic treatment fails. Despite the tendency to reclassify SLE patients in clinical and immunological subsets, we hope that these data will inspire medical professionals to approach NPSLE in a manner more tailored to the individual patient. PMID:28178431

Lowering of blood pressure by chronic suppression of central sympathetic outflow: insight from prolonged baroreflex activation

PubMed Central

Iliescu, Radu

2012-01-01

Device-based therapy for resistant hypertension by electrical activation of the carotid baroreflex is currently undergoing active clinical investigation, and initial findings from clinical trials have been published. The purpose of this mini-review is to summarize the experimental studies that have provided a conceptual understanding of the mechanisms that account for the long-term lowering of arterial pressure with baroreflex activation. The well established mechanisms mediating the role of the baroreflex in short-term regulation of arterial pressure by rapid changes in peripheral resistance and cardiac function are often extended to long-term pressure control, and the more sluggish actions of the baroreflex on renal excretory function are often not taken into consideration. However, because clinical, experimental, and theoretical evidence indicates that the kidneys play a dominant role in long-term control of arterial pressure, this review focuses on the mechanisms that link baroreflex-mediated reductions in central sympathetic outflow with increases in renal excretory function that lead to sustained reductions in arterial pressure. PMID:22797307

Neuropsychiatric Systemic Lupus Erythematosus Involvement: Towards a Tailored Approach to Our Patients?

PubMed

Faria, Raquel; Gonçalves, João; Dias, Rita

2017-01-30

Neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) is a complex condition that remains poorly understood, and includes heterogeneous manifestations involving both the central and peripheral nervous system, with disabling effects. There are several models to improve NPSLE diagnosis when a neurological syndrome is present. In the last couple of years, the growing knowledge of the role of cytokines and antibodies in NPSLE, as well as the development of new functional imaging techniques, has brought some insights into the physiopathology of the disease, but their validation for clinical use remains undetermined. Furthermore, besides the classic clinical approach, a new tool for screening the 19 NPSLE syndromes has also been developed. Regarding NPSLE therapeutics, there is still no evidence-based treatment approach, but some data support the safety of biological medication when classic treatment fails. Despite the tendency to reclassify SLE patients in clinical and immunological subsets, we hope that these data will inspire medical professionals to approach NPSLE in a manner more tailored to the individual patient.

Nailfold video-capillaroscopy in systemic sclerosis.

PubMed

Cutolo, M; Pizzorni, C; Sulli, A

2004-12-01

The Raynaud's phenomenon (RP) is the most common and significant clinical condition supporting microvascular analysis as soon as possible. Microvascular involvement is a key feature of RP, and several rheumatic diseases are characterized by the presence of the RP. Nailfold capillary microscopy shows an impressive cost/effectiveness ratio: it is simple, noninvasive and inexpensive.Well-recognized videocapillaroscopic patterns (NVC) have been described mainly in scleroderma (SSc) patients complaining of a secondary RP. The peripheral microvascular damage in SSc is characterized by increasing structural alterations of the capillaries (giant capillaries and microhemorrhages) with progressive decrease of their density. The detection of the scleroderma NCV allows early differentiation between primary RP (functional, not disease associated), and secondary RP (disease associated). Other major NVC patterns have been described in the field of rheumatic diseases. Interestingly, correlations are evident between the NCV and the clinical symptoms, severity of the disease and the laboratory findings. Further clinical and epidemiological studies, as well as a standardized and computerized quantitation of the observed damages are required.

Imaging the Perivascular Space as a Potential Biomarker of Neurovascular and Neurodegenerative Diseases.

PubMed

Ramirez, Joel; Berezuk, Courtney; McNeely, Alicia A; Gao, Fuqiang; McLaurin, JoAnne; Black, Sandra E

2016-03-01

Although the brain lacks conventional lymphatic vessels found in peripheral tissue, evidence suggests that the space surrounding the vasculature serves a similar role in the clearance of fluid and metabolic waste from the brain. With aging, neurodegeneration, and cerebrovascular disease, these microscopic perivascular spaces can become enlarged, allowing for visualization and quantification on structural MRI. The purpose of this review is to: (i) describe some of the recent pre-clinical findings from basic science that shed light on the potential neurophysiological mechanisms driving glymphatic and perivascular waste clearance, (ii) review some of the pathobiological etiologies that may lead to MRI-visible enlarged perivascular spaces (ePVS), (iii) describe the possible clinical implications of ePVS, (iv) evaluate existing qualitative and quantitative techniques used for measuring ePVS burden, and (v) propose future avenues of research that may improve our understanding of this potential clinical neuroimaging biomarker for fluid and metabolic waste clearance dysfunction in neurodegenerative and neurovascular diseases.

Anomalies of the CD8+ T cell pool in haemochromatosis: HLA-A3-linked expansions of CD8+CD28- T cells.

PubMed

Arosa, F A; Oliveira, L; Porto, G; da Silva, B M; Kruijer, W; Veltman, J; de Sousa, M

1997-03-01

The present study consists of a phenotypic and functional characterization of peripheral blood T lymphocytes in a group of 21 patients with hereditary haemochromatosis (HH), an MHC class I-linked genetic disease resulting in iron overload, and a group of 30 healthy individuals, both HLA-phenotyped. The HH patients studied showed an increased percentage of CD8+ CD28- T cells with a corresponding reduction in the percentage of CD8+ CD28+ T cells in peripheral blood relative to healthy blood donors. No anomalies of CD28 expression were found in the CD4+ subset. The presence of the HLA-A3 antigen but not age accounted for these imbalances. Thus, an apparent failure of the CD8+ CD28+ T cell population 'to expand', coinciding with an 'expansion' of CD8+ CD28- T cells in peripheral blood of HLA-A3+ but not HLA-A3- HH patients was observed when compared with the respective HLA-A3-matched control group. A significantly higher percentage of HLA-DR+ but not CD45RO+ cells was also found within the peripheral CD8+ T cell subset in HH patients relative to controls. Phytohaemagglutinin (PHA) stimulation of peripheral blood mononuclear cells (PBMC) for 5 days showed: (i) that CD8+ CD28+ T cells both in controls and HH were able to expand in vitro; (ii) that CD8+ CD28- T cells decreased markedly after activation in controls but not in HH patients. Moreover, functional studies showed that CD8+ cytotoxic T lymphocytes (CTL) from HH patients exhibited a diminished cytotoxic activity (approx. two-fold) in standard 51Cr-release assays when compared with CD8+ CTL from healthy controls. The present results provide additional evidence for the existence of phenotypic and functional anomalies of the peripheral CD8+ T cell pool that may underlie the clinical heterogeneity of this iron overload disease. They are of particular relevance given the recent discovery of a novel mutated MHC class I-like gene in HH.

Anomalies of the CD8+ T cell pool in haemochromatosis: HLA-A3-linked expansions of CD8+CD28− T cells

PubMed Central

AROSA, F A; OLIVEIRA, L; PORTO, G; DA SILVA, B M; KRUIJER, W; VELTMAN, J; DE SOUSA, M

1997-01-01

The present study consists of a phenotypic and functional characterization of peripheral blood T lymphocytes in a group of 21 patients with hereditary haemochromatosis (HH), an MHC class I-linked genetic disease resulting in iron overload, and a group of 30 healthy individuals, both HLA-phenotyped. The HH patients studied showed an increased percentage of CD8+ CD28− T cells with a corresponding reduction in the percentage of CD8+ CD28+ T cells in peripheral blood relative to healthy blood donors. No anomalies of CD28 expression were found in the CD4+ subset. The presence of the HLA-A3 antigen but not age accounted for these imbalances. Thus, an apparent failure of the CD8+ CD28+ T cell population ‘to expand’, coinciding with an ‘expansion’ of CD8+ CD28− T cells in peripheral blood of HLA-A3+ but not HLA-A3− HH patients was observed when compared with the respective HLA-A3-matched control group. A significantly higher percentage of HLA-DR+ but not CD45RO+ cells was also found within the peripheral CD8+ T cell subset in HH patients relative to controls. Phytohaemagglutinin (PHA) stimulation of peripheral blood mononuclear cells (PBMC) for 5 days showed: (i) that CD8+ CD28+ T cells both in controls and HH were able to expand in vitro; (ii) that CD8+ CD28− T cells decreased markedly after activation in controls but not in HH patients. Moreover, functional studies showed that CD8+ cytotoxic T lymphocytes (CTL) from HH patients exhibited a diminished cytotoxic activity (approx. two-fold) in standard 51Cr-release assays when compared with CD8+ CTL from healthy controls. The present results provide additional evidence for the existence of phenotypic and functional anomalies of the peripheral CD8+ T cell pool that may underlie the clinical heterogeneity of this iron overload disease. They are of particular relevance given the recent discovery of a novel mutated MHC class I-like gene in HH. PMID:9067531

Gene Expression Differences in Peripheral Blood of Parkinson’s Disease Patients with Distinct Progression Profiles

PubMed Central

Soreq, Lilach; Lobo, Patrícia P.; Mestre, Tiago; Coelho, Miguel; Rosa, Mário M.; Gonçalves, Nilza; Wales, Pauline; Mendes, Tiago; Gerhardt, Ellen; Fahlbusch, Christiane; Bonifati, Vincenzo; Bonin, Michael; Miltenberger-Miltényi, Gabriel; Borovecki, Fran; Soreq, Hermona; Ferreira, Joaquim J.; F. Outeiro, Tiago

2016-01-01

The prognosis of neurodegenerative disorders is clinically challenging due to the inexistence of established biomarkers for predicting disease progression. Here, we performed an exploratory cross-sectional, case-control study aimed at determining whether gene expression differences in peripheral blood may be used as a signature of Parkinson’s disease (PD) progression, thereby shedding light into potential molecular mechanisms underlying disease development. We compared transcriptional profiles in the blood from 34 PD patients who developed postural instability within ten years with those of 33 patients who did not develop postural instability within this time frame. Our study identified >200 differentially expressed genes between the two groups. The expression of several of the genes identified was previously found deregulated in animal models of PD and in PD patients. Relevant genes were selected for validation by real-time PCR in a subset of patients. The genes validated were linked to nucleic acid metabolism, mitochondria, immune response and intracellular-transport. Interestingly, we also found deregulation of these genes in a dopaminergic cell model of PD, a simple paradigm that can now be used to further dissect the role of these molecular players on dopaminergic cell loss. Altogether, our study provides preliminary evidence that expression changes in specific groups of genes and pathways, detected in peripheral blood samples, may be correlated with differential PD progression. Our exploratory study suggests that peripheral gene expression profiling may prove valuable for assisting in prediction of PD prognosis, and identifies novel culprits possibly involved in dopaminergic cell death. Given the exploratory nature of our study, further investigations using independent, well-characterized cohorts will be essential in order to validate our candidates as predictors of PD prognosis and to definitively confirm the value of gene expression analysis in aiding patient stratification and therapeutic intervention. PMID:27322389

The detection of melanoma cells in peripheral blood by reverse transcription-polymerase chain reaction.

PubMed Central

Foss, A. J.; Guille, M. J.; Occleston, N. L.; Hykin, P. G.; Hungerford, J. L.; Lightman, S.

1995-01-01

Both cutaneous and uveal melanoma undergo haematogenous dissemination. Detection of tyrosinase mRNA by reverse transcription-polymerase chain reaction (RT-PCR) has been described as an extremely sensitive way of detecting circulating viable melanoma cells in the peripheral venous blood, and this technique may be of value in the early detection of dissemination. Also, it has been suggested that surgical manipulation of the eye, such as occurs during enucleation, can provoke uveal melanoma dissemination. The purpose of this study was to evaluate whether tyrosinase mRNA is detectable in the peripheral blood of patients with uveal and cutaneous melanoma and in patients with uveal melanoma undergoing surgical procedures on the eye harbouring the tumour. Venous blood samples from 36 patients diagnosed as having active uveal melanoma and from six patients with advanced metastatic cutaneous melanoma were analysed. In addition, blood samples were spiked with known numbers of cells from three cell lines and four primary uveal melanoma cultures. The reported sensitivity of the technique was confirmed, with an ability to detect down to one cell per ml of blood. All 51 blood samples from the 36 patients with uveal melanoma were negative, and this included 20 perioperative blood samples. The test was also negative for the six patients with advanced cutaneous melanoma. There were two positives among 31 control samples analysed. This study demonstrates that there are far fewer circulating viable melanocytes than has been previously supposed in patients with melanoma and that the RT-PCR is of no clinical value in detecting metastatic melanoma disease. There was no evidence for surgery causing a bolus of melanoma cells to enter the peripheral circulation. Images Figure 1 Figure 2 PMID:7599046

Improving efficiency and value in health care. Intravenous iron management for anaemia associated with chronic kidney disease: linking treatment to an outpatient clinic, optimizing service provision and patient choice.

PubMed

Bhandari, Sunil; Naudeer, Sarah

2008-12-01

The National Service Framework advocates correction of anaemia in patients with chronic kidney disease (CKD). Oral iron is insufficient, while intravenous (IV) supplementation replenishes and maintains iron stores. In Yorkshire numerous peripheral clinics exist to reduce travel for patients, but patients must travel to the main unit for IV iron therapy. Therefore an outpatient service in tandem with a routine clinic for administration of IV CosmoFer was created. To evaluate the feasibility and benefits of IV iron therapy in the outpatient clinic during active patient review for CKD patients. A cross-sectional study of patients attending for total dose IV iron (n = 57) at a peripheral clinic. Iron was administered and monitored according to protocol by one of the clinic nurses with medical staff available in the adjoining room. Haemoglobin, ferritin and renal function were recorded pre-infusion and after 4-6 months. Results are given as medians/means +/- standard error. A total of 76 IV infusions were carried out with no reported side effects or haemodynamic instability. Haemoglobin (median 10.9 vs. 11.3 g dL(-1), P = NS), creatinine and estimated glomerular filtration rate (eGFR) over the 6-month period remained stable. Serum ferritin rose significantly [80.9 +/- 6.2 vs. 186.4 +/- 18.2 g L(-1) (P < 0.001)]. Hospital time saved 380 day case bed hours, doctor hours saved 76 hours, and patient hours saved 3 hours/patient. Cost savings for TDI CosmoFer in peripheral clinic versus in centre therapy and versus sucrose, respectively, for 76 treatments was pound 5749.40 and pound 46,320.80 respectively. We have demonstrated, in a resource-limited service, the feasibility and cost-effectiveness of a management care pathway for patients with CKD, in a peripheral clinic, to receive total dose IV CosmoFer without disruption of a functioning renal clinic.

Artificial sensory organs: latest progress.

PubMed

Nakamura, Tatsuo; Inada, Yuji; Shigeno, Keiji

2018-03-01

This study introduces the latest progress on the study of artificial sensory organs, with a special emphasis on the clinical results of artificial nerves and the concept of in situ tissue engineering. Peripheral nerves have a strong potential for regeneration. An artificial nerve uses this potential to recover a damaged peripheral nerve. The polyglycolic acid collagen tube (PGA-C tube) is a bio-absorbable tube stuffed with collagen of multi-chamber structure that consists of thin collagen films. The clinical application of the PGA-C tube began in 2002 in Japan. The number of PGA-C tubes used is now beyond 300, and satisfactory results have been reported on peripheral nerve repairs. This PGA-C tube is also effective for patients suffering from neuropathic pain.

Overview of classification systems in peripheral artery disease.

PubMed

Hardman, Rulon L; Jazaeri, Omid; Yi, J; Smith, M; Gupta, Rajan

2014-12-01

Peripheral artery disease (PAD), secondary to atherosclerotic disease, is currently the leading cause of morbidity and mortality in the western world. While PAD is common, it is estimated that the majority of patients with PAD are undiagnosed and undertreated. The challenge to the treatment of PAD is to accurately diagnose the symptoms and determine treatment for each patient. The varied presentations of peripheral vascular disease have led to numerous classification schemes throughout the literature. Consistent grading of patients leads to both objective criteria for treating patients and a baseline for clinical follow-up. Reproducible classification systems are also important in clinical trials and when comparing medical, surgical, and endovascular treatment paradigms. This article reviews the various classification systems for PAD and advantages to each system.

HEMATOPOIETIC STEM CELL INFUSION/TRANSPLANTATION FOR INDUCTION OF ALLOGRAFT TOLERANCE

PubMed Central

Granados, Jose M. Marino; Benichou, Gilles; Kawai, Tatsuo

2015-01-01

Purpose of review This review updates the current status of basic, preclinical, and clinical research on donor hematopoietic stem cell infusion for allograft tolerance induction. Recent findings Recent basic studies in mice provide evidence of significant involvement of both central deletional and peripheral regulatory mechanisms in induction and maintenance of allograft tolerance effected through a mixed chimerism approach with donor hematopoietic stem cell infusion. The presence of heterologous memory T cells in primates hampers the induction of persistent chimerism. Durable mixed chimerism, however, now has been recently induced in inbred major histocompatibility complex-mismatched swine, resulting in tolerance of vascularized composite tissue allografts. In clinical transplantation, allograft tolerance has been achieved in human leukocyte antigen-mismatched kidney transplantation after the induction of transient mixed chimerism or persistent full donor chimerism. Summary Tolerance induction in clinical kidney transplantation has been achieved by donor hematopoietic stem cell infusion. Improving the consistency and safety of tolerance induction and extending successful protocols to other organs, as well as to organs from deceased donors, are critical next steps to bringing tolerance to a wider range of clinical applications. PMID:25563992

Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review

PubMed Central

Kirksey, Meghan A.; Haskins, Stephen C.; Cheng, Jennifer; Liu, Spencer S.

2015-01-01

Background The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants. Objectives To systematically review adjuvant-related randomized controlled trials and meta-analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks. Methods Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and published without an Investigational New Drug application or equivalent status were excluded. Results Sixty one novel clinical trials and meta-analyses were identified and included in this review. The clinical trials reported analgesic duration data for the following adjuvants: buprenorphine (6), morphine (6), fentanyl (10), epinephrine (3), clonidine (7), dexmedetomidine (7), dexamethasone (7), tramadol (8), and magnesium (4). Studies of perineural buprenorphine, clonidine, dexamethasone, dexmedetomidine, and magnesium most consistently demonstrated prolongation of peripheral nerve blocks. Conclusions Buprenorphine, clonidine, dexamethasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and concerns for side effects and potential toxicity persist. PMID:26355598

The peripheral artery questionnaire: a new disease-specific health status measure for patients with peripheral arterial disease.

PubMed

Spertus, John; Jones, Philip; Poler, Sherri; Rocha-Singh, Krishna

2004-02-01

The most common indication for treating patients with peripheral arterial disease is to improve their health status: their symptoms, function, and quality of life. Quantifying health status requires a valid, reproducible, and sensitive disease-specific measure. The Peripheral Artery Questionnaire (PAQ) is a 20-item questionnaire developed to meet this need by quantifying patients' physical limitations, symptoms, social function, treatment satisfaction, and quality of life. Psychometric and clinical properties of the PAQ were evaluated in a prospective cohort study of 44 patients undergoing elective percutaneous peripheral revascularization. To establish reproducibility, 2 assessments were performed 2 weeks apart and before revascularization. The change in scores before and 6 weeks after revascularization were used to determine the instruments' responsiveness and were compared with the Short Form-36 and the Walking Impairment Questionnaire. A series of cross-sectional analyses were performed to establish the construct validity of the PAQ. The 7 domains of the PAQ were internally reliable, with Cronbach alpha = 0.80 to 0.94. The test-retest reliability analyses revealed insignificant mean changes of 0.6 to 2.3 points (P = not significant for all). Conversely, the change after revascularization ranged from 13.7 to 41.9 points (P < or =.001 for all), reflecting substantial sensitivity of the PAQ to clinical improvement. The PAQ Summary Scale was the most sensitive of all scales tested. Construct validity was established by demonstrating correlations with other measures of patient health status. The PAQ is a valid, reliable, and responsive disease-specific measure for patients with peripheral arterial disease. It may prove to be a useful end point in clinical trials and a potential aid in disease management.

Peripheral Atherectomy: Applications and Techniques.

PubMed

Mittleider, Derek; Russell, Erich

2016-06-01

Peripheral atherectomy is a class of procedures that is rapidly increasing in volume. Multiple classes of devices exist, and newer variants are added to the market annually. The devices see wide application for de novo lesions, in-stent restenosis, and adjunctive therapy for drug-coated balloons. The body of evidence supporting atherectomy is less robust than for many other peripheral therapies. The frequency and severity of complications from atherectomy can be significant compared with angioplasty and stenting, and familiarity with preventative and bailout techniques is essential for the interventionalist. Copyright © 2016 Elsevier Inc. All rights reserved.

Parkinson's disease and systemic inflammation.

PubMed

Ferrari, Carina C; Tarelli, Rodolfo

2011-02-22

Peripheral inflammation triggers exacerbation in the central brain's ongoing damage in several neurodegenerative diseases. Systemic inflammatory stimulus induce a general response known as sickness behaviour, indicating that a peripheral stimulus can induce the synthesis of cytokines in the brain. In Parkinson's disease (PD), inflammation was mainly associated with microglia activation that can underlie the neurodegeneration of neurons in the substantia nigra (SN). Peripheral inflammation can transform the "primed" microglia into an "active" state, which can trigger stronger responses dealing with neurodegenerative processes. Numerous evidences show that systemic inflammatory processes exacerbate ongoing neurodegeneration in PD patient and animal models. Anti-inflammatory treatment in PD patients exerts a neuroprotective effect. In the present paper, we analyse the effect of peripheral infections in the etiology and progression in PD patients and animal models, suggesting that these peripheral immune challenges can exacerbate the symptoms in the disease.

Self-Injurious Behaviour in Intellectual Disability Syndromes: Evidence for Aberrant Pain Signalling as a Contributing Factor

ERIC Educational Resources Information Center

Peebles, K. A.; Price, T. J.

2012-01-01

Background: In most individuals, injury results in activation of peripheral nociceptors (pain-sensing neurons of the peripheral nervous system) and amplification of central nervous system (CNS) pain pathways that serve as a disincentive to continue harmful behaviour; however, this may not be the case in some developmental disorders that cause…

Association of Peripheral Blood Levels of Brain-Derived Neurotrophic Factor With Autism Spectrum Disorder in Children: A Systematic Review and Meta-analysis.

PubMed

Qin, Xiao-Yan; Feng, Jin-Chao; Cao, Chang; Wu, Huan-Tong; Loh, Y Peng; Cheng, Yong

2016-11-01

Accumulating evidence suggests that brain-derived neurotrophic factor (BDNF) may be implicated in the developmental outcomes of children with autism spectrum disorder (ASD). To use meta-analysis to determine whether children with ASD have altered peripheral blood levels of BDNF. A systematic search of PubMed, PsycINFO, and Web of Science was performed for English-language literature through February 7, 2016. The search terms included brain-derived neurotrophic factor or BDNF in combination with autism, without year restriction. Two additional records were retrieved after a review of the reference lists of selected articles. Studies were included if they provided data on peripheral blood levels of BDNF in children with ASD and healthy control children. Studies that included adults or with overlapping samples were excluded. Data were extracted by 2 independent observers from 19 included studies. Data were pooled using a random-effects model with Comprehensive Meta-analysis software. Blood levels of BDNF in children with ASD compared with healthy controls. Altered levels of BDNF were hypothesized to be related to ASD. This meta-analysis included 19 studies with 2896 unique participants. Random-effects meta-analysis of all 19 studies showed that children with ASD had significantly increased peripheral blood levels of BDNF compared with healthy controls (Hedges g, 0.490; 95% CI, 0.185-0.794; P = .002). Subgroup analyses in 4 studies revealed that neonates diagnosed with ASD later in life had no association with blood levels of BDNF (Hedges g, 0.384; 95% CI, -0.244 to 1.011; P = .23), whereas children in the nonneonate ASD group (15 studies) demonstrated significantly increased BDNF levels compared with healthy controls (Hedges g, 0.524; 95% CI, 0.206 to 0.842; P = .001). Further analysis showed that children in the nonneonate ASD group had increased BDNF levels in serum (10 studies) (Hedges g, 0.564; 95% CI, 0.168 to 0.960; P = .005) but not in plasma (5 studies) (Hedges g, 0.436; 95% CI, -0.176 to 1.048; P = .16). Meta-regression analyses revealed that sample size had a moderating effect on the outcome of the meta-analysis in the nonneonate group. In addition, no publication bias was found in the meta-analysis. Children with ASD have increased peripheral blood levels of BDNF, strengthening the clinical evidence of an abnormal neurotrophic factor profile in this population.

Chelation therapy to treat atherosclerosis, particularly in diabetes: Is it time to reconsider?

PubMed Central

Lamas, Gervasio A; Ergui, Ian

2016-01-01

Summary Reports and case series have suggested a possible beneficial effect of chelation therapy in patients with atherosclerotic disease. Small randomized trials conducted in patients with angina or peripheral artery disease, however, were not sufficiently powered to provide conclusive evidence on clinical outcomes. The Trial to Assess Chelation Therapy (TACT) was the first randomized trial adequately powered to detect the effects of chelation therapy on clinical endpoints. Chelation reduced adverse cardiovascular events in a post myocardial infarction (MI) population. Patients with diabetes demonstrated even greater benefit, with a number needed to treat of 6.5 patients to prevent a cardiac event over 5 years. These results led to the revision of the ACC/AHA guideline recommendations for chelation therapy, changing its classification from class III to class IIb. TACT2, a replicative trial, will assess the effects of chelation therapy on cardiovascular outcomes in diabetic patients with a prior myocardial infarction. PMID:27149141

Experts' beliefs on physiotherapy for patients with ankylosing spondylitis and assessment of their knowledge on published evidence in the field. Results of a questionnaire among international ASAS members.

PubMed

Mihai, B; van der Linden, S; de Bie, R; Stucki, G

2005-06-01

The aim of this study was to assess both the opinion of an international group of experts about the place and importance of physiotherapy in the management of ankylosing spondylitis (AS) as well as the awareness of the responders about scientific evidence on efficacy and cost-effectiveness of physiotherapy in AS. An e-mail questionnaire ''Experts' Beliefs on Physiotherapy for Patients with Ankylosing Spondylitis'' has been sent to all 71 international ASsessment of Ankylosing Spondylitis (ASAS) members. Completion of the twenty-eight-item questionnaire was done through the ASAS website (www.ASAS-group.org). The number of responders was 53 (response rate 73%). Altogether 94% of the responders regard themselves as experts in the field of clinical care for AS patients. There is almost unanimous (86-92%) consensus on the efficacy of physiotherapy (widely defined, i.e. as physical therapy-including exercises, application of physical modalities and spa-therapy) for patients with axial and peripheral joint manifestations of AS. Physiotherapy is considered to be indicated for both early AS (less than 2 years after diagnosis) (88%) and AS of longer duration (2 to 10 years) (94%), implying that this non-pharmaceutical intervention should be made available for or should be prescribed to AS patients. Also daily exercises at home are considered indicated for both early (less than 2 years after diagnosis) AS (90%) and AS of longer duration of disease (90%). High-level evidence (Cochrane reviews or publications of one or more randomized controlled clinical trials) favoring efficacy of physiotherapy was considered available by 33% of the participants, whereas 43% replied ''no'' and 24% did not know. Finally, excluding the costs of the intervention, 39% of the participants reported that Spa-therapy might reduce health care costs as usage of NSAIDs, physician visits and ability to work or sick leave, whereas 26% said ''no'' and 35% did not know. The international ASAS experts hold a favorable opinion on the efficacy of physiotherapy in AS, including group exercises and spa therapy, almost irrespective of disease duration and type of articular involvement (axial/peripheral). Awareness of published evidence on physiotherapy in AS is unsatisfactory.

Modest Elevation in BNP in Asymptomatic Hypertensive Patients Reflects Sub-Clinical Cardiac Remodeling, Inflammation and Extracellular Matrix Changes

PubMed Central

Martos, Ramon; Collier, Patrick; Patle, Anil; Donnelly, Seamas; Ledwidge, Mark; Baugh, John

2012-01-01

In asymptomatic subjects B-type natriuretic peptide (BNP) is associated with adverse cardiovascular outcomes even at levels well below contemporary thresholds used for the diagnosis of heart failure. The mechanisms behind these observations are unclear. We examined the hypothesis that in an asymptomatic hypertensive population BNP would be associated with sub-clinical evidence of cardiac remodeling, inflammation and extracellular matrix (ECM) alterations. We performed transthoracic echocardiography and sampled coronary sinus (CS) and peripheral serum from patients with low (n = 14) and high BNP (n = 27). Peripheral BNP was closely associated with CS levels (r = 0.92, p<0.001). CS BNP correlated significantly with CS levels of markers of collagen type I and III turnover including: PINP (r = 0.44, p = 0.008), CITP (r = 0.35, p = 0.03) and PIIINP (r = 0.35, p = 0.001), and with CS levels of inflammatory cytokines including: TNF-α (r = 0.49, p = 0.002), IL-6 (r = 0.35, p = 0.04), and IL-8 (r = 0.54, p<0.001). The high BNP group had greater CS expression of fibro-inflammatory biomarkers including: CITP (3.8±0.7 versus 5.1±1.9, p = 0.007), TNF-α (3.2±0.5 versus 3.7±1.1, p = 003), IL-6 (1.9±1.3 versus 3.4±2.7, p = 0.02) and hsCRP (1.2±1.1 versus 2.4±1.1, p = 0.04), and greater left ventricular mass index (97±20 versus 118±26 g/m2, p = 0.03) and left atrial volume index (18±2 versus 21±4, p = 0.008). Our data provide insight into the mechanisms behind the observed negative prognostic impact of modest elevations in BNP and suggest that in an asymptomatic hypertensive cohort a peripheral BNP measurement may be a useful marker of an early, sub-clinical pathological process characterized by cardiac remodeling, inflammation and ECM alterations. PMID:23152884

The Impact of Local and Regional Disease Extent on Overall Survival in Patients With Advanced Stage IIIB/IV Non-Small Cell Lung Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higginson, Daniel S., E-mail: daniel.higginson@gmail.com; Chen, Ronald C.; Tracton, Gregg

2012-11-01

Purpose: Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy. A variety of factors (eg, performance status, gender, age, histology, weight loss, and smoking history) are generally accepted as predictors of overall survival. Because uncontrolled pulmonary disease constitutes a major cause of death in these patients, we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors. The results have implications regarding the selection of patients for whom palliative thoracic radiation therapy may be of most benefit. Methods andmore » Materials: We conducted a pooled analysis of 189 patients enrolled at a single institution into 9 prospective phase II and III clinical trials involving first-line, platinum-based chemotherapy. Baseline clinical and radiographic characteristics before trial enrollment were analyzed as possible predictors for subsequent overall survival. To assess the relationship between anatomic location and volume of disease within the thorax and its effect on survival, the pre-enrollment computed tomography images were also analyzed by contouring central and peripheral intrapulmonary disease. Results: On univariate survival analysis, multiple pulmonary-related factors were significantly associated with worse overall survival, including pulmonary symptoms at presentation (P=.0046), total volume of intrathoracic disease (P=.0006), and evidence of obstruction of major bronchi or vessels on prechemotherapy computed tomography (P<.0001). When partitioned into central and peripheral volumes, central (P<.0001) but not peripheral (P=.74) disease was associated with worse survival. On multivariate analysis with known factors, pulmonary symptoms (hazard ratio, 1.46; P=.042), central disease volume (hazard ratio, 1.47; P=.042), and bronchial/vascular compression (hazard ratio, 1.54; P=.022) remained significant. Conclusions: Patients with bulky central disease, bronchial/vascular compression, and/or pulmonary symptoms exhibited worse overall survival after first-line, platinum-based chemotherapy. A subset of these patients may be studied to determine whether early, planned palliative thoracic radiation could also be of benefit.« less

Integrated versus nOn-integrated Peripheral inTravenous catheter. Which Is the most effective systeM for peripheral intravenoUs catheter Management? (The OPTIMUM study): a randomised controlled trial protocol

PubMed Central

Castillo, Maria Isabel; Larsen, Emily; Cooke, Marie; Marsh, Nicole M; Wallis, Marianne C; Finucane, Julie; Brown, Peter; Mihala, Gabor; Byrnes, Joshua; Walker, Rachel; Cable, Prudence; Zhang, Li; Sear, Candi; Jackson, Gavin; Rowsome, Anna; Ryan, Alison; Humphries, Julie C; Sivyer, Susan; Flanigan, Kathy; Rickard, Claire M

2018-01-01

Introduction Peripheral intravenous catheters (PIVCs) are frequently used in hospitals. However, PIVC complications are common, with failures leading to treatment delays, additional procedures, patient pain and discomfort, increased clinician workload and substantially increased healthcare costs. Recent evidence suggests integrated PIVC systems may be more effective than traditional non-integrated PIVC systems in reducing phlebitis, infiltration and costs and increasing functional dwell time. The study aim is to determine the efficacy, cost–utility and acceptability to patients and professionals of an integrated PIVC system compared with a non-integrated PIVC system. Methods and analysis Two-arm, multicentre, randomised controlled superiority trial of integrated versus non-integrated PIVC systems to compare effectiveness on clinical and economic outcomes. Recruitment of 1560 patients over 2 years, with randomisation by a centralised service ensuring allocation concealment. Primary outcomes: catheter failure (composite endpoint) for reasons of: occlusion, infiltration/extravasation, phlebitis/thrombophlebitis, dislodgement, localised or catheter-associated bloodstream infections. Secondary outcomes: first time insertion success, types of PIVC failure, device colonisation, insertion pain, functional dwell time, adverse events, mortality, cost–utility and consumer acceptability. One PIVC per patient will be included, with intention-to-treat analysis. Baseline group comparisons will be made for potentially clinically important confounders. The proportional hazards assumption will be checked, and Cox regression will test the effect of group, patient, device and clinical variables on failure. An as-treated analysis will assess the effect of protocol violations. Kaplan-Meier survival curves with log-rank tests will compare failure by group over time. Secondary endpoints will be compared between groups using parametric/non-parametric techniques. Ethics and dissemination Ethical approval from the Royal Brisbane and Women’s Hospital Human Research Ethics Committee (HREC/16/QRBW/527), Griffith University Human Research Ethics Committee (Ref No. 2017/002) and the South Metropolitan Health Services Human Research Ethics Committee (Ref No. 2016–239). Results will be published in peer-reviewed journals. Trial registration number ACTRN12617000089336. PMID:29764876

Integrated versus nOn-integrated Peripheral inTravenous catheter. Which Is the most effective systeM for peripheral intravenoUs catheter Management? (The OPTIMUM study): a randomised controlled trial protocol.

PubMed

Castillo, Maria Isabel; Larsen, Emily; Cooke, Marie; Marsh, Nicole M; Wallis, Marianne C; Finucane, Julie; Brown, Peter; Mihala, Gabor; Carr, Peter J; Byrnes, Joshua; Walker, Rachel; Cable, Prudence; Zhang, Li; Sear, Candi; Jackson, Gavin; Rowsome, Anna; Ryan, Alison; Humphries, Julie C; Sivyer, Susan; Flanigan, Kathy; Rickard, Claire M

2018-05-14

Peripheral intravenous catheters (PIVCs) are frequently used in hospitals. However, PIVC complications are common, with failures leading to treatment delays, additional procedures, patient pain and discomfort, increased clinician workload and substantially increased healthcare costs. Recent evidence suggests integrated PIVC systems may be more effective than traditional non-integrated PIVC systems in reducing phlebitis, infiltration and costs and increasing functional dwell time. The study aim is to determine the efficacy, cost-utility and acceptability to patients and professionals of an integrated PIVC system compared with a non-integrated PIVC system. Two-arm, multicentre, randomised controlled superiority trial of integrated versus non-integrated PIVC systems to compare effectiveness on clinical and economic outcomes. Recruitment of 1560 patients over 2 years, with randomisation by a centralised service ensuring allocation concealment. Primary outcomes: catheter failure (composite endpoint) for reasons of: occlusion, infiltration/extravasation, phlebitis/thrombophlebitis, dislodgement, localised or catheter-associated bloodstream infections. first time insertion success, types of PIVC failure, device colonisation, insertion pain, functional dwell time, adverse events, mortality, cost-utility and consumer acceptability. One PIVC per patient will be included, with intention-to-treat analysis. Baseline group comparisons will be made for potentially clinically important confounders. The proportional hazards assumption will be checked, and Cox regression will test the effect of group, patient, device and clinical variables on failure. An as-treated analysis will assess the effect of protocol violations. Kaplan-Meier survival curves with log-rank tests will compare failure by group over time. Secondary endpoints will be compared between groups using parametric/non-parametric techniques. Ethical approval from the Royal Brisbane and Women's Hospital Human Research Ethics Committee (HREC/16/QRBW/527), Griffith University Human Research Ethics Committee (Ref No. 2017/002) and the South Metropolitan Health Services Human Research Ethics Committee (Ref No. 2016-239). Results will be published in peer-reviewed journals. ACTRN12617000089336. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

PubMed Central

Starobova, Hana; Vetter, Irina

2017-01-01

Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic function which develop in a glove and stocking distribution due to preferential effects on longer axons. The pathophysiological processes are multi-factorial and involve oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration and membrane remodeling as well as immune processes and neuroinflammation. This review focusses on the commonly used antineoplastic substances oxaliplatin, cisplatin, vincristine, docetaxel, and paclitaxel which interfere with the cancer cell cycle—leading to cell death and tumor degradation—and cause severe acute and chronic peripheral neuropathies. We discuss drug mechanism of action and pharmacokinetic disposition relevant to the development of peripheral neuropathy, the epidemiology and clinical presentation of chemotherapy-induced neuropathy, emerging insight into genetic susceptibilities as well as current understanding of the pathophysiology and treatment approaches. PMID:28620280

Specimen Orientation by Marking the Peripheral End: (Potential) Clinical Advantages in Prostate Biopsy

PubMed Central

Galosi, Andrea Benedetto; Muzzonigro, Giovanni; Lacetera, Vito; Mazzucchelli, Roberta

2011-01-01

The aim of this paper is to identify advantages that could be obtained by orientation of the biopsy specimen using the marking technique. We reviewed our experience (4,500 cases) and the published literature. The peripheral (proximal) end of the fresh specimen is marked with ink soon after needle delivering in a few minutes. It is performed easily in association with pre-embedding method. Five potential clinical advantages were identified: (1) tumor localization, (2) atypical lesions localization and planning rebiopsy strategy, (3) planning surgical strategy, (4) selection criteria for focal therapy and active surveillance, and (5) cost reduction. Peripheral end marking is low cost, easy and reproducible. It drives several potential advantages in cancer diagnosis or isolated atypical lesions, in particular, spatial localization within the biopsy (transition versus peripheral zone, anterior versus posterior, subcapsular versus intraparenchima, and extraprostatic extension) should be easy and reliable. We can add a new pathological parameter: pathological orientation or biopsy polarity. PMID:22096654

Does a Flatter General Gradient of Visual Attention Explain Peripheral Advantages and Central Deficits in Deaf Adults?

PubMed Central

Samar, Vincent J.; Berger, Lauren

2017-01-01

Individuals deaf from early age often outperform hearing individuals in the visual periphery on attention-dependent dorsal stream tasks (e.g., spatial localization or movement detection), but sometimes show central visual attention deficits, usually on ventral stream object identification tasks. It has been proposed that early deafness adaptively redirects attentional resources from central to peripheral vision to monitor extrapersonal space in the absence of auditory cues, producing a more evenly distributed attention gradient across visual space. However, little direct evidence exists that peripheral advantages are functionally tied to central deficits, rather than determined by independent mechanisms, and previous studies using several attention tasks typically report peripheral advantages or central deficits, not both. To test the general altered attentional gradient proposal, we employed a novel divided attention paradigm that measured target localization performance along a gradient from parafoveal to peripheral locations, independent of concurrent central object identification performance in prelingually deaf and hearing groups who differed in access to auditory input. Deaf participants without cochlear implants (No-CI), with cochlear implants (CI), and hearing participants identified vehicles presented centrally, and concurrently reported the location of parafoveal (1.4°) and peripheral (13.3°) targets among distractors. No-CI participants but not CI participants showed a central identification accuracy deficit. However, all groups displayed equivalent target localization accuracy at peripheral and parafoveal locations and nearly parallel parafoveal-peripheral gradients. Furthermore, the No-CI group’s central identification deficit remained after statistically controlling peripheral performance; conversely, the parafoveal and peripheral group performance equivalencies remained after controlling central identification accuracy. These results suggest that, in the absence of auditory input, reduced central attentional capacity is not necessarily associated with enhanced peripheral attentional capacity or with flattening of a general attention gradient. Our findings converge with earlier studies suggesting that a general graded trade-off of attentional resources across the visual field does not adequately explain the complex task-dependent spatial distribution of deaf-hearing performance differences reported in the literature. Rather, growing evidence suggests that the spatial distribution of attention-mediated performance in deaf people is determined by sophisticated cross-modal plasticity mechanisms that recruit specific sensory and polymodal cortex to achieve specific compensatory processing goals. PMID:28559861

Expression of CD34 and CD68 in peripheral giant cell granuloma and central giant cell granuloma: An immunohistochemical analysis.

PubMed

Vk, Varsha; Hallikeri, Kaveri; Girish, H C; Murgod, Sanjay

2014-01-01

Central and Peripheral giant cell granulomas of jaws are uncommon, benign, reactive disorders that are characterized by the presence of numerous multinucleated giant cells and mononuclear cells within a stroma. The origin of the multinucleated giant cells is controversial; probably originating from fusion of histiocytes, endothelial cells and fibroblasts. To assess the expression of CD34 and CD68 in central and peripheral giant cell granulomas to understand the origin of these multinucleated giant cells. Twenty cases of Central and Peripheral giant cell granulomas were evaluated immunohistochemically for CD34 and CD68 proteins expression. Immunopositivity for CD34 was seen only in cytoplasm of endothelial cells of blood vessels; whereas, consistent cytoplasmic immunopositivity for CD68 was seen in few stromal cells. Statistical significance was seen in mean number of multinucleated giant cells, mean number of nuclei in multinucleated giant cells, CD68 expression and ratio of macrophages to multinucleated giant cells among two lesions. Although the central giant cell granulomas share some clinical and histopathological similarities with peripheral giant cell granulomas, differences in mean number of nuclei in multinucleated giant cells and CD68 immunoreactivity may underlie the distinct clinical behavior.

Obstetrical brachial plexus injury (OBPI): Canada's national clinical practice guideline

PubMed Central

Coroneos, Christopher J; Voineskos, Sophocles H; Christakis, Marie K; Thoma, Achilleas; Bain, James R; Brouwers, Melissa C

2017-01-01

Objective The objective of this study was to establish an evidence-based clinical practice guideline for the primary management of obstetrical brachial plexus injury (OBPI). This clinical practice guideline addresses 4 existing gaps: (1) historic poor use of evidence, (2) timing of referral to multidisciplinary care, (3) Indications and timing of operative nerve repair and (4) distribution of expertise. Setting The guideline is intended for all healthcare providers treating infants and children, and all specialists treating upper extremity injuries. Participants The evidence interpretation and recommendation consensus team (Canadian OBPI Working Group) was composed of clinicians representing each of Canada's 10 multidisciplinary centres. Outcome measures An electronic modified Delphi approach was used for consensus, with agreement criteria defined a priori. Quality indicators for referral to a multidisciplinary centre were established by consensus. An original meta-analysis of primary nerve repair and review of Canadian epidemiology and burden were previously completed. Results 7 recommendations address clinical gaps and guide identification, referral, treatment and outcome assessment: (1) physically examine for OBPI in newborns with arm asymmetry or risk factors; (2) refer newborns with OBPI to a multidisciplinary centre by 1 month; (3) provide pregnancy/birth history and physical examination findings at birth; (4) multidisciplinary centres should include a therapist and peripheral nerve surgeon experienced with OBPI; (5) physical therapy should be advised by a multidisciplinary team; (6) microsurgical nerve repair is indicated in root avulsion and other OBPI meeting centre operative criteria; (7) the common data set includes the Narakas classification, limb length, Active Movement Scale (AMS) and Brachial Plexus Outcome Measure (BPOM) 2 years after birth/surgery. Conclusions The process established a new network of opinion leaders and researchers for further guideline development and multicentre research. A structured referral form is available for primary care, including referral recommendations. PMID:28132014

On-treatment decrease of NKG2D correlates to early emergence of clinically evident hepatocellular carcinoma after interferon-free therapy for chronic hepatitis C.

PubMed

Chu, Po-Sung; Nakamoto, Nobuhiro; Taniki, Nobuhito; Ojiro, Keisuke; Amiya, Takeru; Makita, Yuko; Murata, Hiroko; Yamaguchi, Akihiro; Shiba, Shunsuke; Miyake, Rei; Katayama, Tadashi; Ugamura, Aya; Ikura, Akihiko; Takeda, Karin; Ebinuma, Hirotoshi; Saito, Hidetsugu; Kanai, Takanori

2017-01-01

Interferon (IFN)- free direct antiviral agents (DAAs) with rapid HCV eradication might evoke immunological reconstitutions, and some early recurrences of HCC after IFN-free DAAs have been reported. This study aimed to investigate whether natural killer group 2, member D (NKG2D) predicts early emergence of HCC after IFN-free DAAs. We conducted a clinical practice-based observational study of 101 patients infected with genotype 1 HCV who received IFN-free (DAAs), and stratified them into those who did or did not develop early (i.e., during the 6-month surveillance period following treatment.) recurrence or occurrence of clinically evident HCC. We also analyzed the peripheral blood mononuclear cells, both before treatment and at end of treatment (EOT), of 24 of the patients who received IFN-free DAAs, and 16 who received IFN-combined protease inhibitor. We found early emergence of clinically evident HCC after IFN-free DAAs in 12 (12%) patients. Higher pre-treatment NKG2D expression, higher FIB-4 score, previous HCC history and failure to achieve sustained viral response were significant factors correlating to early HCC emergence. After IFN-free DAAs, a rapid decrease of NKG2D at EOT correlated with early HCC emergence in the IFN-free DAA-treated patients, but not in patients treated with the IFN-combined regimen. The decrease of NKG2D until EOT was predictive of early HCC emergence at a cut-off of -52% (AUC = 0.92). On-treatment decrease of NKG2D may be a useful predictor of early emerging HCC in patients treated with IFN-free DAAs.

[RESEARCH PROGRESS OF PERIPHERAL NERVE SURGERY ASSISTED BY Da Vinci ROBOTIC SYSTEM].

PubMed

Shen, Jie; Song, Diyu; Wang, Xiaoyu; Wang, Changjiang; Zhang, Shuming

2016-02-01

To summarize the research progress of peripheral nerve surgery assisted by Da Vinci robotic system. The recent domestic and international articles about peripheral nerve surgery assisted by Da Vinci robotic system were reviewed and summarized. Compared with conventional microsurgery, peripheral nerve surgery assisted by Da Vinci robotic system has distinctive advantages, such as elimination of physiological tremors and three-dimensional high-resolution vision. It is possible to perform robot assisted limb nerve surgery using either the traditional brachial plexus approach or the mini-invasive approach. The development of Da Vinci robotic system has revealed new perspectives in peripheral nerve surgery. But it has still been at the initial stage, more basic and clinical researches are still needed.

Coexistence of Guillain-Barré syndrome and Behçet's disease.

PubMed

Shugaiv, Erkingul; Kiyat-Atamer, Asli; Tüzün, Erdem; Deymeer, Feza; Oflazer, Piraye; Parman, Yesim; Akman-Demir, Gulsen

2013-01-01

Behçet's disease (BD) is a multisystemic, recurrent and inflammatory disorder. Neurological involvement is rare and affects mainly the central nervous system (CNS) in the form of brainstem meningoencephalitis or dural sinus thrombosis. Peripheral neuropathy is usually not observed during the course of BD but some reports have shown electrophysiologic evidence of subclinical neuropathy, mononeuritis multiplex and cranial neuropathy in BD patients. The co-occurrence of Guillain-Barré syndrome (GBS), an acute inflammatory demyelinating neuropathy, with other autoimmune or systemic diseases is rare. We present a case of BD with clinical and electrophysiological diagnosis of GBS. The findings of the patient were discussed with reference to literature.

Post-thymic maturation: young T cells assert their individuality.

PubMed

Fink, Pamela J; Hendricks, Deborah W

2011-07-22

T cell maturation was once thought to occur entirely within the thymus. Now, evidence is mounting that the youngest peripheral T cells in both mice and humans comprise a distinct population from their more mature, yet still naive, counterparts. These cells, termed recent thymic emigrants (RTEs), undergo a process of post-thymic maturation that can be monitored at the levels of cell phenotype and immune function. Understanding this final maturation step in the process of generating useful and safe T cells is of clinical relevance, given that RTEs are over-represented in neonates and in adults recovering from lymphopenia. Post-thymic maturation may function to ensure T cell fitness and self tolerance.

The Biology and Clinical Utility of EBV Monitoring in Blood.

PubMed

Kanakry, Jennifer; Ambinder, Richard

2015-01-01

Epstein-Barr virus (EBV) DNA in blood can be quantified in peripheral blood mononuclear cells, in circulating cell-free (CCF) DNA specimens, or in whole blood. CCF viral DNA may be actively released or extruded from viable cells, packaged in virions or passively shed from cells during apoptosis or necrosis. In infectious mononucleosis, viral DNA is detected in each of these kinds of specimens, although it is only transiently detected in CCF specimens. In nasopharyngeal carcinoma, CCF EBV DNA is an established tumor marker. In EBV-associated Hodgkin lymphoma and in EBV-associated extranodal NK-/T-cell lymphoma, there is growing evidence for the utility of CCF DNA as a tumor marker.

Current therapeutic strategies for premature ejaculation and future perspectives

PubMed Central

Xin, Zhong-Cheng; Zhu, Yi-Chen; Yuan, Yi-Ming; Cui, Wan-Shou; Jin, Zhe; Li, Wei-Ren; Liu, Tao

2011-01-01

Premature ejaculation (PE) is a common sexual disorder in men that is mediated by disturbances in the peripheral and central nervous systems. Although all pharmaceutical treatments for PE are currently used ‘off-label', some novel oral agents and some newer methods of drug administration now provide important relief to PE patients. However, the aetiology of this condition has still not been unified, primarily because of the lack of a standard animal model for basic research and the absence of a widely accepted definition and assessment tool for evidence-based clinical studies in patients with PE. In this review, we focus on the current therapeutic strategies and future treatment perspectives for PE. PMID:21532601

Lymphatic drainage in renal cell carcinoma: back to the basics.

PubMed

Karmali, Riaz J; Suami, Hiroo; Wood, Christopher G; Karam, Jose A

2014-12-01

Lymphatic drainage in renal cell carcinoma (RCC) is unpredictable, however, basic patterns can be observed in cadaveric and sentinel lymph node mapping studies in patients with RCC. The existence of peripheral lymphovenous communications at the level of the renal vein has been shown in mammals but remains unknown in humans. The sentinel lymph node biopsy technique can be safely applied to map lymphatic drainage patterns in patients with RCC. Further standardisation of sentinel node biopsy techniques is required to improve the clinical significance of mapping studies. Understanding lymphatic drainage in RCC may lead to an evidence-based consensus on the surgical management of retroperitoneal lymph nodes. © 2014 The Authors. BJU International © 2014 BJU International.

Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve Repair and Functional Outcomes

DTIC Science & Technology

2016-07-01

AWARD NUMBER: W81XWH-15-2-0026 TITLE: Clinical Evaluation of Decellularized Nerve Allograft With Autologous Bone Marrow Stem Cells To Improve...5b. GRANT NUMBER W81XWH-15-2-0026 CClinical Evaluation of Decellularized Nerve Allograft With Autologous Bone Marrow Stem Cells To Improve...co- treatments of a commercially available decellularized processed peripheral nerve allograft scaffold (Avance® Nerve Graft, AxoGen, Alachua FL) with

Differences in diagnosis, follow-up and treatment of patients with dementia living in the peripheral areas compared with the central areas of Israel.

PubMed

Merims, D; Shemesh, D Golan; Nahari, H; Arharov, O; Ari, G Ben; Israel, J Ben

2015-07-01

We compared data regarding diagnosis, treatment and follow-up of patients with dementia in the central and the peripheral areas of Israel. Data were collected from the medical records of 164 patients with advanced dementia, all residents of dementia special care units - 97 patients from a central nursing home and 67 patients from the peripheral areas. The data collected related to the period prior to hospitalization and included: demographic data, imaging tests, follow-up by a memory clinic and drug treatment prior to admission. Mini Mental State Examination on admission was also recorded. Patients in the peripheral areas were hospitalized while having better cognitive function, as demonstrated by the Mini Mental State Examination (p < 0.05). More patients in the central areas versus the peripheral areas were aided by an in-house worker prior to admission (p < 0.001). More patients with dementia in the central areas were followed up by a memory clinic (p < 0.001) and underwent brain imaging (p < 0.01) compared with patients with dementia living in the peripheral areas. Although not significant, patients from the central areas were more commonly treated with atypical neuroleptics for behavioral problems (p = 0.05). On the basis of the current data, we suggest that there are differences in the diagnosis, follow-up and drug treatment among patients with dementia living in the central areas versus those living in the peripheral ones. Patients in the peripheral areas are hospitalized while their cognitive abilities are relatively better than those of the patients in central areas. © The Author(s) 2013.

Premature aging-related peripheral neuropathy in a mouse model of progeria.

PubMed

Goss, James R; Stolz, Donna Beer; Robinson, Andria Rasile; Zhang, Mingdi; Arbujas, Norma; Robbins, Paul D; Glorioso, Joseph C; Niedernhofer, Laura J

2011-08-01

Peripheral neuropathy is a common aging-related degenerative disorder that interferes with daily activities and leads to increased risk of falls and injury in the elderly. The etiology of most aging-related peripheral neuropathy is unknown. Inherited defects in several genome maintenance mechanisms cause tissue-specific accelerated aging, including neurodegeneration. We tested the hypothesis that a murine model of XFE progeroid syndrome, caused by reduced expression of ERCC1-XPF DNA repair endonuclease, develops peripheral neuropathy. Nerve conduction studies revealed normal nerve function in young adult (8 week) Ercc1(-/Δ) mice, but significant abnormalities in 20 week-old animals. Morphologic and ultrastructural analysis of the sciatic nerve from mutant mice revealed significant alterations at 20 but not 8 weeks of age. We conclude that Ercc1(-/Δ) mice have accelerated spontaneous peripheral neurodegeneration that mimics aging-related disease. This provides strong evidence that DNA damage can drive peripheral neuropathy and offers a rapid and novel model to test therapies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Composite pheochromocytoma with a malignant peripheral nerve sheath tumor: Case report and review of the literature.

PubMed

Namekawa, Takeshi; Utsumi, Takanobu; Imamoto, Takashi; Kawamura, Koji; Oide, Takashi; Tanaka, Tomoaki; Nihei, Naoki; Suzuki, Hiroyoshi; Nakatani, Yukio; Ichikawa, Tomohiko

2016-07-01

Adrenal tumors with more than one cellular component are uncommon. Furthermore, an adrenal tumor composed of a pheochromocytoma and a malignant peripheral nerve sheath tumor is extremely rare. A composite pheochromocytoma with malignant peripheral nerve sheath tumor in a 42-year-old man is reported here. After adequate preoperative control, left adrenalectomy was performed simultaneously with resection of the ipsilateral kidney for spontaneous rupture of the left adrenal tumor. Pathological findings demonstrated pheochromocytoma and malignant peripheral nerve sheath tumor in a ruptured adrenal tumor. To date, there have been only four reported cases of composite pheochromocytoma with malignant peripheral nerve sheath tumor, so the present case is only the fifth case in the world. Despite the very poor prognosis of patients with pheochromocytoma and malignant peripheral nerve sheath tumors reported in the literature, the patient remains well without evidence of recurrence or new metastatic lesions at 36 months postoperatively. Copyright © 2012. Published by Elsevier Taiwan.

Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial.

PubMed

Attal, Nadine; de Andrade, Daniel C; Adam, Frédéric; Ranoux, Danièle; Teixeira, Manoel J; Galhardoni, Ricardo; Raicher, Irina; Üçeyler, Nurcan; Sommer, Claudia; Bouhassira, Didier

2016-05-01

Data from previous studies suggest that botulinum toxin A has analgesic effects against peripheral neuropathic pain, but the quality of the evidence is low. We aimed to assess the safety and efficacy of repeated administrations of botulinum toxin A in patients with neuropathic pain. We did a randomised, double-blind, placebo-controlled trial at two outpatient clinics in France (Clinical Pain Centre, Ambroise Paré Hospital, APHP, Boulogne-Billancourt, and Neurological Centre, Hôpital Dupuytren, Limoges) and one in Brazil (Neurological Department, Hospital das Clínicas da FMUSP, São Paulo). Patients aged 18-85 years with peripheral neuropathic pain were randomly assigned (1:1) by block randomisation, according to a centralised schedule, to receive two subcutaneous administrations of botulinum toxin A (up to 300 units) or placebo, 12 weeks apart. All patients and investigators were masked to treatment assignment. The primary outcome was the efficacy of botulinum toxin A versus placebo, measured as the change from baseline in self-reported mean weekly pain intensity over the course of 24 weeks from the first administration. The primary efficacy analysis was a mixed-model repeated-measures analysis in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01251211. Between Oct 2, 2010, and Aug 2, 2013, 152 patients were enrolled, of whom 68 were randomly assigned (34 per group), and 66 (37 [56%] men) were included in the primary analysis (34 in the botulinum toxin A group and 32 in the placebo group). Botulinum toxin A reduced pain intensity over 24 weeks compared with placebo (adjusted effect estimate -0·77, 95% CI -0·95 to -0·59; p<0·0001). Pain on injection was the only adverse effect reported, and occurred in 19 (56%) participants in the botulinum toxin A group and 17 (53%) of those in the placebo group (p=1·0). Severe pain was experienced by ten (29%) participants in the botulinum toxin A group and 11 (34%) in the placebo group (p=0·8). Two administrations of botulinum toxin A, each of which comprised several injections, have a sustained analgesic effect against peripheral neuropathic pain. Several factors, such as the presence of allodynia and a limited thermal deficit, may be useful in predicting treatment response and should be investigated further. Institut National de la Santé et de la Recherche Médicale (INSERM) and Fondation CNP (France). Copyright © 2016 Elsevier Ltd. All rights reserved.

[Clinical and laboratory characteristics of chronic active Epstein-Barr virus infection in children].

PubMed

Mao, Jun-Qing; Yang, Shi-Long; Song, Hua; Zhao, Fen-Ying; Xu, Xiao-Jun; Gu, Min-Er; Tang, Yong-Min

2014-11-01

To study the clinical and laboratory characteristics of chronic active Epstein-Barr virus (EBV) infection (CAEBV) in children and to provide a basis for the diagnosis and treatment of CAEBV. The clinical data of 13 children with CAEBV, as well as 15 cases of acute EBV infection (AEBV) as controls, were analyzed, including clinical manifestations, EBV antibodies, EBV DNA, and peripheral blood lymphocyte subsets. Both groups of patients had infectious mononucleosis-like symptoms such as fever, hepatomegaly, splenomegaly, and lymphadenectasis, but CAEBV patients had a longer course of disease and continuous and recurrent symptoms. Compared with the AEBV group, the CAEBV group had a significantly higher EBV DNA load in peripheral blood (P<0.05), a significantly higher VCA-IgG titer (P<0.05), and significantly lower numbers of white blood cells, lymphocytes, B cells, total T cells, CD4+ T cells, and CD8+ T cells in peripheral blood (P<0.05). Among 13 CAEBV patients followed up, 8 cases died, 2 cases showed an improvement, 2 cases had a recurrence, and 1 case was lost to follow-up after being transferred to another hospital. All the AEBV patients were cured and had no recurrence during the one-year follow-up. The clinical manifestations of CAEBV vary in children. It is difficult to distinguish CAEBV from AEBV early. More attention should be paid to CAEBV because of its severe complications, poor prognosis, and high mortality. Measurement of EBV DNA load, VCA-IgG titer, and lymphocyte subsets in peripheral blood may be helpful in the diagnosis and differential diagnosis of CAEBV.

Cortical motor activity and reorganization following upper-limb amputation and subsequent targeted reinnervation.

PubMed

Chen, Albert; Yao, Jun; Kuiken, Todd; Dewald, Julius P A

2013-01-01

Previous studies have postulated that the amount of brain reorganization following peripheral injuries may be correlated with negative symptoms or consequences. However, it is unknown whether restoring effective limb function may then be associated with further changes in the expression of this reorganization. Recently, targeted reinnervation (TR), a surgical technique that restores a direct neural connection from amputated sensorimotor nerves to new peripheral targets such as muscle, has been successfully applied to upper-limb amputees. It has been shown to be effective in restoring both peripheral motor and sensory functions via the reinnervated nerves as soon as a few months after the surgery. However, it was unclear whether TR could also restore normal cortical motor representations for control of the missing limb. To answer this question, we used high-density electroencephalography (EEG) to localize cortical activity related to cued motor tasks generated by the intact and missing limb. Using a case study of 3 upper-limb amputees, 2 of whom went through pre and post-TR experiments, we present unique quantitative evidence for the re-mapping of motor representations for the missing limb closer to their original locations following TR. This provides evidence that an effective restoration of peripheral function from TR can be linked to the return of more normal cortical expression for the missing limb. Therefore, cortical mapping may be used as a potential guide for monitoring rehabilitation following peripheral injuries.

Locating the cortical bottleneck for slow reading in peripheral vision

PubMed Central

Yu, Deyue; Jiang, Yi; Legge, Gordon E.; He, Sheng

2015-01-01

Yu, Legge, Park, Gage, and Chung (2010) suggested that the neural bottleneck for slow peripheral reading is located in nonretinotopic areas. We investigated the potential rate-limiting neural site for peripheral reading using fMRI, and contrasted peripheral reading with recognition of peripherally presented line drawings of common objects. We measured the BOLD responses to both text (three-letter words/nonwords) and line-drawing objects presented either in foveal or peripheral vision (10° lower right visual field) at three presentation rates (2, 4, and 8/second). The statistically significant interaction effect of visual field × presentation rate on the BOLD response for text but not for line drawings provides evidence for distinctive processing of peripheral text. This pattern of results was obtained in all five regions of interest (ROIs). At the early retinotopic cortical areas, the BOLD signal slightly increased with increasing presentation rate for foveal text, and remained fairly constant for peripheral text. In the Occipital Word-Responsive Area (OWRA), Visual Word Form Area (VWFA), and object sensitive areas (LO and PHA), the BOLD responses to text decreased with increasing presentation rate for peripheral but not foveal presentation. In contrast, there was no rate-dependent reduction in BOLD response for line-drawing objects in all the ROIs for either foveal or peripheral presentation. Only peripherally presented text showed a distinctive rate-dependence pattern. Although it is possible that the differentiation starts to emerge at the early retinotopic cortical representation, the neural bottleneck for slower reading of peripherally presented text may be a special property of peripheral text processing in object category selective cortex. PMID:26237299

Evidence and Implications of Mortality Associated with Acute Plasmodium vivax Malaria

PubMed Central

2013-01-01

Vivax malaria threatens patients despite relatively low-grade parasitemias in peripheral blood. The tenet of death as a rare outcome, derived from antiquated and flawed clinical classifications, disregarded key clinical evidence, including (i) high rates of mortality in neurosyphilis patients treated with vivax malaria; (ii) significant mortality from zones of endemicity; and (iii) the physiological threat inherent in repeated, very severe paroxysms in any patient, healthy or otherwise. The very well-documented course of this infection, with the exception of parasitemia, carries all of the attributes of “perniciousness” historically linked to falciparum malaria, including severe disease and fatal outcomes. A systematic analysis of the parasite biomass in severely ill patients that includes blood, marrow, and spleen may ultimately explain this historic misunderstanding. Regardless of how this parasite is pernicious, recent data demonstrate that the infection comes with a significant burden of morbidity and associated mortality. The extraordinary burden of malaria is not heavily weighted upon any single continent by a single species of parasite—it is a complex problem for the entire endemic world, and both species are of fundamental importance. Humanity must rally substantial resources, intellect, and energy to counter this daunting but profound threat. PMID:23297258

Clinical utility of a DNA probe to 17p11.2 in screening of patients with a peripheral neuropathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blancato, J.; Precht, K.; Meck, J.

1994-09-01

We assessed the usefulness of in situ hybridization with a DNA probe to the area of chromosome 17 at p11.2 as a diagnostic tool for screening for Charcot Marte Tooth 1A (CMT 1A). In situ hybridization with a probe to 17p11.2 was performed on fixed lymphocytes from the following groups of individuals: (1) normal controls; (2) patients evoking a strong clinical suspicion of CMT 1A; and (3) 3 families with an apparent autosomal dominant peripheral neuropathy of unknown diagnoses. Group 2 patients had evidence of demyelination as defined by nerve conduction of less that 50% of the normal mean ormore » terminal latency greater than 50% of the normal mean in conduction studies. Analysis of interphase cells hybridized with a cosmid DNA probe to 17p11.2 requires inclusion of a normal control with each trial and masked observer. Due to the size of the target DNA and the nature of the centromeric heterochromatin, the scoring of this probe is more subjective than centromere probes. For example, if the two 17 chromosomes are decondensed as in interphase, two tandem signals may be visualized as one. Results from duplication positive patients demonstrate a large proportion of cells with two closely aligned, but separate, signals with an additional single signal. Normal results demonstrate a majority of cells with two separate signals representing both normal homologues. None of the 3 families with questionable diagnosis revealed a duplication at the region, reinforcing our belief that a clinical diagnosis is the most discriminating tool available for diagnosis of CMT 1A. We concur with Boylan that molecular analysis for CMT 1A is useful for establishing a diagnosis of CMT 1A, but is not a primary differential diagnostic test. The yield in screening patients without physiologic evidence of demyelination is likely to be low. We further find that the use of in situ hybridization is a simple method of performing the duplication analysis.« less

Premise and promise of mesenchymal stem cell-based therapies in clinical vascularized composite allotransplantation.

PubMed

Schweizer, Riccardo; Gorantla, Vijay S; Plock, Jan A

2015-12-01

Over the past decade, clinical vascularized composite allotransplantation (VCA) has enabled functional and quality of life restoration in a wide range of indications secondary to devastating tissue loss. However, the spectre of toxicity and long-term complications of chronic immunosuppression has curtailed the momentum of VCA. This study summarizes the literature evidence behind successful mesenchymal stem cell (MSC)-based cell therapies highlighting their multipronged immunomodulatory, restorative and regenerative characteristics with special emphasis towards VCA applications. Experimental and clinical studies in solid organs and VCA have confirmed that MSCs facilitate immunosuppression-free allograft survival or tolerance, stimulate peripheral nerve regeneration, attenuate ischaemia-reperfusion injury, and improve tissue healing after surgery. It has been hypothesized that MSC-induced long-term operational tolerance in experimental VCA is mediated by induction of mixed donor-specific chimerism and regulatory T-cell mechanisms. All these characteristics of MSCs could thus help expand the scope and clinical feasibility of VCA. Cellular therapies, especially those focusing on MSCs, are emerging in solid organ transplantation including VCA. Although some clinical trials have begun to assess the effects of MSCs in solid organ transplantation, much scientific domain remains uncharted, especially for VCA.

Peripheral atherectomy practice patterns in the United States from the Vascular Quality Initiative.

PubMed

Mohan, Sathish; Flahive, Julie M; Arous, Edward J; Judelson, Dejah R; Aiello, Francesco A; Schanzer, Andres; Simons, Jessica P

2018-06-21

Peripheral atherectomy has been shown to have technical success in single-arm studies, but clinical advantages over angioplasty and stenting have not been demonstrated, leaving its role unclear. We sought to describe patterns of atherectomy use in a real-world U.S. cohort to understand how it is currently being applied. The Vascular Quality Initiative was queried to identify all patients who underwent peripheral vascular intervention from January 2010 to September 2016. Descriptive statistics were performed to analyze demographics of the patients, comorbidities, indication, treatment modalities, and lesion characteristics. The intermittent claudication (IC) and critical limb ischemia (CLI) cohorts were analyzed separately. Of 85,605 limbs treated, treatment indication was IC in 51% (n = 43,506) and CLI in 49% (n = 42,099). Atherectomy was used in 15% (n = 13,092) of cases, equivalently for IC (15%; n = 6674) and CLI (15%; n = 6418). There was regional variation in use of atherectomy, ranging from a low of 0% in one region to a high of 32% in another region. During the study period, there was a significant increase in the proportion of cases that used atherectomy (11% in 2010 vs 18% in 2016; P < .0001). Compared with nonatherectomy cases, those with atherectomy use had higher incidence of prior peripheral vascular intervention (IC, 55% vs 43% [P < .0001]; CLI, 47% vs 41% [P < .0001]), greater mean number of arteries treated (IC, 1.8 vs 1.6 [P < .0001]; CLI, 2.1 vs 1.7 [P < .0001]), and lower proportion of prior leg bypass (IC, 10% vs 14% [P < .0001]; CLI, 11% vs 17% [P < .0001]). There was lower incidence of failure to cross the lesion (IC, 1% vs 4% [P < .0001]; CLI, 4% vs 7% [P < .0001]) but higher incidence of distal embolization (IC, 1.9% vs 0.8% [P < .0001]; CLI, 3.0% vs 1.4% [P < .0001]) and, in the CLI cohort, arterial perforation (1.4% vs 1.0%; P = .01). Despite a lack of evidence for atherectomy over angioplasty and stenting, its use has increased across the United States from 2010 to 2016. It is applied equally to IC and CLI populations, with no identifiable pattern of comorbidities or lesion characteristics, suggesting that indications are not clearly delineated or agreed on. This study places impetus on further understanding of the optimal role for atherectomy and its long-term clinical benefit in the management of peripheral arterial disease. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

An affinity/avidity model of peripheral T cell regulation

PubMed Central

Jiang, Hong; Wu, Yilun; Liang, Bitao; Zheng, Zongyu; Tang, Guomei; Kanellopoulos, Jean; Soloski, Mark; Winchester, Robert; Goldstein, Itamar; Chess, Leonard

2005-01-01

We show in these studies that Qa-1–dependent CD8+ T cells are involved in the establishment and maintenance of peripheral self tolerance as well as facilitating affinity maturation of CD4+ T cells responding to foreign antigen. We provide experimental evidence that the strategy used by the Qa-1–dependent CD8+ T cells to accomplish both these tasks in vivo is to selectively downregulate T cell clones that respond to both self and foreign antigens with intermediate, not high or low, affinity/avidity. Thus, the immune system evolved to regulate peripheral immunity using a unified mechanism that efficiently and effectively permits the system to safeguard peripheral self tolerance yet promote the capacity to deal with foreign invaders. PMID:15668735

Processing and Memory of Central versus Peripheral Information as a Function of Reading Goals: Evidence from Eye-Movements

ERIC Educational Resources Information Center

Yeari, Menahem; van den Broek, Paul; Oudega, Marja

2015-01-01

The present study examined the effect of reading goals on the processing and memory of central and peripheral textual information. Using eye-tracking methodology, we compared the effect of four common reading goals--entertainment, presentation, studying for a close-ended (multiple-choice) questions test, and studying for an open-ended questions…

Generalised peripheral oedema associated with amlodipine therapy in two dogs.

PubMed

Creevy, K E; Scuderi, M A; Ellis, A E

2013-11-01

This report details two cases of adverse drug reactions to amlodipine. The first case presented with diffuse peripheral oedema and a history of amlodipine therapy. Haematology, clinical chemistry, endocrine testing, thoracic, abdominal and cardiac imaging revealed no cause for oedema. Amlodipine therapy was discontinued and oedema diminished markedly within 72 hours. The second case presented for bilateral retinal detachments secondary to systemic hypertension. Haematology, clinical chemistry, thoracic and abdominal imaging were unremarkable and amlodipine therapy was begun. Within 72 hours, diffuse peripheral oedema developed that was unresponsive to therapy and the dog was euthanised. Veterinarians should be aware of the potential serious adverse events associated with commonly used drugs; severe, diffuse oedema is a possible adverse drug event in dogs treated with amlodipine. © 2013 British Small Animal Veterinary Association.

Peripheral T-cell lymphoma with unusual clinical presentation of rhabdomyolysis.

PubMed

Liu, Zhiyu; Medeiros, L Jeffrey; Young, Ken H

2017-03-01

Primary extranodal lymphoma is known to occur in nose, gastrointestinal tract, skin, bone, and central nervous system. However, it is extremely rare for primary lymphoma to arise in skeletal muscle. We report a case of a 32-year-old man who presented initially with fever and fatigue. He had a history of alcohol abuse. Laboratory studies and computerized tomography scan showed results consistent with rhabdomyolysis, but the cause of the rhabdomyolysis was undetermined. After biopsy of abdominal skeletal muscle with histologic examination and T-cell receptor gamma chain gene rearrangement analysis, the diagnosis of peripheral T-cell lymphoma was established. After two cycles of the cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide regimen, the patient's symptoms greatly improved. This is the third reported case of peripheral T-cell lymphoma arising in skeletal muscle reported in the literature and which presented clinically with rhabdomyolysis. The alcohol abuse during the clinical course likely worsens the pathologic process of the rhabdomyolysis. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Severe brachial plexopathy after an ultrasound-guided single-injection nerve block for total shoulder arthroplasty in a patient with multiple sclerosis.

PubMed

Koff, Matthew D; Cohen, Jeffrey A; McIntyre, John J; Carr, Charles F; Sites, Brian D

2008-02-01

DESPITE the known benefits of regional anesthesia for patients undergoing joint arthroplasty, the performance of peripheral nerve blocks in patients with multiple sclerosis (MS) remains controversial. MS has traditionally been described as an isolated disease of the central nervous system, without involvement of the peripheral nerves, and peripheral nerve blockade has been suggested to be safe. However, careful review of the literature suggests that MS may also be associated with involvement of the peripheral nervous system, challenging traditional teachings. There is a paucity of evidence with regard to safety in using peripheral nerve regional anesthesia in these patients. This makes it difficult to provide adequate "informed consent" to these patients. This case report describes a patient with MS who sustained a severe brachial plexopathy after a total shoulder arthroplasty during combined general anesthesia and interscalene nerve block.

Parkinson's Disease and Systemic Inflammation

PubMed Central

Ferrari, Carina C.; Tarelli, Rodolfo

2011-01-01

Peripheral inflammation triggers exacerbation in the central brain's ongoing damage in several neurodegenerative diseases. Systemic inflammatory stimulus induce a general response known as sickness behaviour, indicating that a peripheral stimulus can induce the synthesis of cytokines in the brain. In Parkinson's disease (PD), inflammation was mainly associated with microglia activation that can underlie the neurodegeneration of neurons in the substantia nigra (SN). Peripheral inflammation can transform the “primed” microglia into an “active” state, which can trigger stronger responses dealing with neurodegenerative processes. Numerous evidences show that systemic inflammatory processes exacerbate ongoing neurodegeneration in PD patient and animal models. Anti-inflammatory treatment in PD patients exerts a neuroprotective effect. In the present paper, we analyse the effect of peripheral infections in the etiology and progression in PD patients and animal models, suggesting that these peripheral immune challenges can exacerbate the symptoms in the disease. PMID:21403862

Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project.

PubMed

Weisenburger, Dennis D; Savage, Kerry J; Harris, Nancy Lee; Gascoyne, Randy D; Jaffe, Elaine S; MacLennan, Kenneth A; Rüdiger, Thomas; Pileri, Stefano; Nakamura, Shigeo; Nathwani, Bharat; Campo, Elias; Berger, Francoise; Coiffier, Bertrand; Kim, Won-Seog; Holte, Harald; Federico, Massimo; Au, Wing Y; Tobinai, Kensei; Armitage, James O; Vose, Julie M

2011-03-24

The International Peripheral T-cell Lymphoma Project is a collaborative effort to better understand peripheral T-cell lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was to analyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P < .001). Multivariate analysis of clinical and pathologic prognostic factors, respectively, when controlling for the IPI, identified bulky disease (≥ 10 cm), thrombocytopenia (< 150 × 10(9)/L), and a high number of transformed tumor cells (> 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies.

[Bell's palsy].

PubMed

Prud'hon, S; Kubis, N

2018-03-30

Idiopathic peripheral facial palsy, also named Bell's palsy, is the most common cause of peripheral facial palsy in adults. Although it is considered as a benign condition, its social and psychological impact can be dramatic, especially in the case of incomplete recovery. The main pathophysiological hypothesis is the reactivation of HSV 1 virus in the geniculate ganglia, leading to nerve edema and its compression through the petrosal bone. Patients experience an acute (less than 24 hours) motor deficit involving ipsilateral muscles of the upper and lower face and reaching its peak within the first three days. Frequently, symptoms are preceded or accompanied by retro-auricular pain and/or ipsilateral face numbness. Diagnosis is usually clinical but one should look for negative signs to eliminate central facial palsy or peripheral facial palsy secondary to infectious, neoplastic or autoimmune diseases. About 75% of the patients will experience spontaneous full recovery, this rate can be improved with oral corticotherapy when introduced within the first 72 hours. To date, no benefit has been demonstrated by adding an antiviral treatment. Hemifacial spasms (involuntary muscles contractions of the hemiface) or syncinesia (involuntary muscles contractions elicited by voluntary ones, due to aberrant reinnervation) may complicate the disease's course. Electroneuromyography can be useful at different stages: it can first reveal the early conduction bloc, then estimate the axonal loss, then bring evidence of the reinnervation process and, lastly, help for the diagnosis of complications. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Additives to local anesthetics for peripheral nerve blocks: Evidence, limitations, and recommendations.

PubMed

Bailard, Neil S; Ortiz, Jaime; Flores, Roland A

2014-03-01

The therapeutic rationale, clinical effectiveness, and potential adverse effects of medications used in combination with local anesthetics for peripheral nerve block therapy are reviewed. A wide range of agents have been tested as adjuncts to peripheral nerve blocks, which are commonly performed for regional anesthesia during or after hand or arm surgery, neck or spine surgery, and other procedures. Studies to determine the comparative merits of nerve block adjuncts are complicated by the wide variety of coadministered local anesthetics and sites of administration and by the heterogeneity of primary endpoints. Sodium bicarbonate has been shown to speed the onset of mepivacaine nerve blocks but delay the onset of others. Epinephrine has been shown to prolong sensory nerve blockade and delay systemic uptake of local anesthetics, thus reducing the risk of anesthetic toxicity. Tramadol, buprenorphine, dexamethasone, and clonidine appear to be effective additives in some situations. Midazolam, magnesium, dexmedetomidine, and ketamine cannot be routinely recommended as nerve block additives due to a dearth of supportive data, modest efficacy, and (in the case of ketamine) significant adverse effects. Recent studies suggest that administering additives intravenously or intramuscularly can provide many of the benefits of perineural administration while reducing the potential for neurotoxicity, contamination, and other hazards. Some additives to local anesthetics can hasten the onset of nerve block, prolong block duration, or reduce toxicity. On the other hand, poorly selected or unnecessary additives may not have the desired effect and may even expose patients to unnecessary risks.

Physiological and pharmacologic aspects of peripheral nerve blocks

PubMed Central

Vadhanan, Prasanna; Tripaty, Debendra Kumar; Adinarayanan, S.

2015-01-01

A successful peripheral nerve block not only involves a proper technique, but also a thorough knowledge and understanding of the physiology of nerve conduction and pharmacology of local anesthetics (LAs). This article focuses on what happens after the block. Pharmacodynamics of LAs, underlying mechanisms of clinically observable phenomena such as differential blockade, tachyphylaxis, C fiber resistance, tonic and phasic blockade and effect of volume and concentration of LAs. Judicious use of additives along with LAs in peripheral nerve blocks can prolong analgesia. An entirely new group of drugs-neurotoxins has shown potential as local anesthetics. Various methods are available now to prolong the duration of peripheral nerve blocks. PMID:26330722

Global DNA hypomethylation in peripheral blood mononuclear cells as a biomarker of cancer risk

USDA-ARS?s Scientific Manuscript database

Global DNA hypomethylation is an early molecular event in carcinogenesis. Whether methylation measured in peripheral blood mononuclear cells (PBMCs) DNA is a clinically reliable biomarker for early detection or cancer risk assessment is to be established. From an original sample-set of 753 male and...

Peripheral iridotomy for pigmentary glaucoma

PubMed Central

Michelessi, Manuele; Lindsley, Kristina

2016-01-01

Background Glaucoma is a chronic optic neuropathy characterized by retinal ganglion cell death resulting in damage to the optic nerve head and the retinal nerve fiber layer. Pigment dispersion syndrome is characterized by a structural disturbance in the iris pigment epithelium (the densely pigmented posterior surface of the iris) that leads to dispersion of the pigment and its deposition on various structures within the eye. Pigmentary glaucoma is a specific form of open-angle glaucoma found in patients with pigment dispersion syndrome. Topcial medical therapy is usually the first-line treatment; however, peripheral laser iridotomy has been proposed as an alternate treatment. Peripheral laser iridotomy involves creating an opening in the iris tissue to allow drainage of fluid from the posterior chamber to the anterior chamber and vice versa. Equalizing the pressure within the eye may help to alleviate the friction that leads to pigment dispersion and prevent visual field deterioration. However, the effectiveness of peripheral laser iridotomy in reducing the development or progression of pigmentary glaucoma is unknown. Objectives The objective of this review was to assess the effects of peripheral laser iridotomy compared with other interventions, including medication, trabeculoplasty, and trabeculectomy, or no treatment, for pigment dispersion syndrome and pigmentary glaucoma. Search methods We searched a number of electronic databases including CENTRAL, MEDLINE and EMBASE and clinical trials websites such as (mRCT) and ClinicalTrials.gov. We last searched the electronic databases on 2 November 2015. Selection criteria We included randomized controlled trials (RCTs) that had compared peripheral laser iridotomy versus no treatment or other treatments for pigment dispersion syndrome and pigmentary glaucoma. Data collection and analysis We used standard methodological procedures for systematic reviews. Two review authors independently screened articles for eligibility, extracted data, and assessed included trials for risk of bias. We did not perform a meta-analysis because of variability in reporting and follow-up intervals for primary and secondary outcomes of interest. Main results We included five RCTs (260 eyes of 195 participants) comparing yttrium-aluminum-garnet (YAG) laser iridotomy versus no laser iridotomy. Three trials included participants with pigmentary glaucoma at baseline, and two trials enrolled participants with pigment dispersion syndrome. Only two trials reported the country of enrollment: one - Italy, the other - United Kingdom. Overall, we assessed trials as having high or unclear risk of bias owing to incomplete or missing data and selective outcome reporting. Data on visual fields were available for one of three trials that included participants with pigmentary glaucoma at baseline. At an average follow-up of 28 months, the risk of progression of visual field damage was uncertain when comparing laser iridotomy with no iridotomy (risk ratio (RR) 1.00, 95% confidence interval (95% CI) 0.16 to 6.25; 32 eyes; very low-quality evidence). The two trials that enrolled participants with pigment dispersion syndrome at baseline reported the proportion of participants with onset of glaucomatous visual field changes during the study period. At three-year follow-up, one trial reported that the risk ratio for conversion to glaucoma was 2.72 (95% CI 0.76 to 9.68; 42 eyes; very low-quality evidence). At 10-year follow-up, the other trial reported that no eye showed visual field progression. One trial reported the mean change in intraocular pressure (IOP) in eyes with pigmentary glaucoma: At an average of nine months of follow-up, the mean difference in IOP between groups was 2.69 mmHg less in the laser iridotomy group than in the control group (95% CI −6.05 to 0.67; 14 eyes; very low-quality evidence). This trial also reported the mean change in anterior chamber depth at an average of nine months of follow-up and reported no meaningful differences between groups (mean difference 0.04 mm, 95% CI −0.07 to 0.15; 14 eyes; very low-quality evidence). No other trial reported mean change in anterior chamber depth. Two trials reported greater flattening of iris configuration in the laser iridotomy group than in the control group among eyes with pigmentary glaucoma; however, investigators provided insufficient data for analysis. No trial reported data related to mean visual acuity, aqueous melanin granules, costs, or quality of life outcomes. Two trials assessed the need for additional treatment for control of IOP. One trial that enrolled participants with pigmentary glaucoma reported that more eyes in the laser iridotomy group required additional treatment between six and 23 months of follow-up than eyes in the control group (RR 1.73, 95% CI 1.08 to 2.75; 46 eyes); however, the other trial enrolled participants with pigment dispersion syndrome and indicated that the difference between groups at three-year follow-up was uncertain (RR 0.91, 95% CI 0.38 to 2.17; 105 eyes). We graded the certainty of evidence for this outcome as very low. Two trials reported that no serious adverse events were observed in either group among eyes with pigment dispersion syndrome. Mild adverse events included postoperative inflammation; two participants required cataract surgery (at 18 and 34 months after baseline), and two participants required a repeat iridotomy. Authors' conclusions We found insufficient evidence of high quality on the effectiveness of peripheral iridotomy for pigmentary glaucoma or pigment dispersion syndrome. Although adverse events associated with peripheral iridotomy may be minimal, the long-term effects on visual function and other patient-important outcomes have not been established. Future research on this topic should focus on outcomes that are important to patients and the optimal timing of treatment in the disease process (eg, pigment dispersion syndrome with normal IOP, pigment dispersion syndrome with established ocular hypertension, pigmentary glaucoma). PMID:26871761

Randomized crossover clinical trial of real and sham peripheral prism glasses for hemianopia

PubMed Central

Bowers, Alex R.; Keeney, Karen; Peli, Eli

2013-01-01

Objective To evaluate the efficacy of real relative to sham peripheral prism glasses for patients with complete homonymous hemianopia and without visual neglect. Methods Patients recruited at 13 clinics were allocated by minimization into a double-masked, crossover trial with two groups. One group received real (57Δ) oblique and sham (≤ 5Δ) horizontal prisms; the other received real horizontal and sham oblique, in counterbalanced order. A masked data collector at each clinic administered questionnaires after each 4-week crossover period. Main outcome measure The primary outcome was the overall difference, across the two periods of the crossover, between the proportion of participants who wanted to continue with (said “yes” to) real prisms and the proportion who said yes to sham prisms. The secondary outcome was the difference in perceived mobility improvement between real and sham prisms. Results Of 73 patients randomized, 61 completed the crossover. A significantly higher proportion said yes to real than sham prisms (64% vs. 36%; odds ratio 5.3, 95% CI 1.8 to 21.0). Participants who continued wear after 6 months reported greater improvement in mobility with real than sham prisms at crossover end (p=0.002); participants who discontinued wear reported no difference. Conclusion Real peripheral prism glasses were more helpful for obstacle avoidance when walking than sham glasses, with no differences between the horizontal and oblique designs. Applications to clinical practice Peripheral prism glasses provide a simple and inexpensive mobility rehabilitation intervention for hemianopia. PMID:24201760

Outcome From a Randomized Controlled Clinical Trial　- Improvement of Peripheral Arterial Disease by Granulocyte Colony-Stimulating Factor-Mobilized Autologous Peripheral-Blood-Mononuclear Cell Transplantation (IMPACT).

PubMed

Horie, Takashi; Yamazaki, Seiji; Hanada, Sayaka; Kobayashi, Shuzo; Tsukamoto, Tatsuo; Haruna, Tetsuya; Sakaguchi, Katsuhiko; Sakai, Ken; Obara, Hideaki; Morishita, Kiyofumi; Saigo, Kenichi; Shintani, Yoshiaki; Kubo, Kohmei; Hoshino, Junichi; Oda, Teiji; Kaneko, Eiji; Nishikido, Masaharu; Ioji, Tetsuya; Kaneda, Hideaki; Fukushima, Masanori

2018-06-07

The clinical usefulness of peripheral blood (PB) mononuclear cell (MNC) transplantation in patients with peripheral arterial disease (PAD), especially in those with mild-to-moderate severity, has not been fully clarified.Methods and Results:A randomized clinical trial was conducted to evaluate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF)-mobilized PBMNC transplantation in patients with PAD (Fontaine stage II-IV and Rutherford category 1-5) caused by arteriosclerosis obliterans or Buerger's disease. The primary endpoint was progression-free survival (PFS). In total, 107 subjects were enrolled. At baseline, Fontaine stage was II/III in 82 patients and IV in 21, and 54 patients were on hemodialysis. A total of 50 patients had intramuscular transplantation of PBMNC combined with standard of care (SOC) (cell therapy group), and 53 received SOC only (control group). PFS tended to be improved in the cell therapy group than in the control group (P=0.07). PFS in Fontaine stage II/III subgroup was significantly better in the cell therapy group than in the control group. Cell therapy-related adverse events were transient and not serious. In this first randomized, large-scale clinical trial of G-CSF-mobilized PBMNC transplantation, the cell therapy was tolerated by a variety of PAD patients. The PBMNC therapy was significantly effective for inhibiting disease progression in mild-to-moderate PAD.

Systemic rapamycin to prevent in-stent stenosis in peripheral pulmonary arterial disease: early clinical experience.

PubMed

Hallbergson, Anna; Esch, Jesse J; Tran, Trang X; Lock, James E; Marshall, Audrey C

2016-10-01

We have taken a novel approach using oral rapamycin - sirolimus - as a medical adjunct to percutaneous therapy in patients with in-stent stenosis and high risk of right ventricular failure. Peripheral pulmonary artery stenosis can result in right ventricular hypertension, dysfunction, and death. Percutaneous pulmonary artery angioplasty and stent placement acutely relieve obstructions, but patients frequently require re-interventions due to re-stenosis. In patients with tetralogy of Fallot or arteriopathy, the problem of in-stent stenosis contributes to the rapidly recurrent disease. Rapamycin was administered to 10 patients (1.5-18 years) with peripheral pulmonary stenosis and in-stent stenosis and either right ventricular hypertension, pulmonary blood flow maldistribution, or segmental pulmonary hypertension. Treatment was initiated around the time of catheterisation and continued for 1-3 months. Potential side-effects were monitored by clinical review and blood tests. Target serum rapamycin level (6-10 ng/ml) was accomplished in all patients; eight of the nine patients who returned for clinically indicated catheterisations demonstrated reduction in in-stent stenosis, and eight of the 10 patients experienced no significant side-effects. Among all, one patient developed diarrhoea requiring drug discontinuation, and one patient experienced gastrointestinal bleeding while on therapy that was likely due to an indwelling feeding tube and this patient tolerated rapamycin well following tube removal. Our initial clinical experience supports that patients with peripheral pulmonary artery stenosis can be safely treated with rapamycin. Systemic rapamycin may provide a novel medical approach to reduce in-stent stenosis.

Perinatal inflammation and adult psychopathology: From preclinical models to humans.

PubMed

Depino, Amaicha Mara

2018-05-01

Perinatal environment plays a crucial role in brain development and determines its function through life. Epidemiological studies and clinical reports link perinatal exposure to infection and/or immune activation to various psychiatric disorders. In addition, accumulating evidence from animal models shows that perinatal inflammation can affect various behaviors relevant to psychiatric disorders such as schizophrenia, autism, anxiety and depression. Remarkably, the effects on behavior and brain function do not always depend on the type of inflammatory stimulus or the perinatal age targeted, so diverse inflammatory events can have similar consequences on the brain. Moreover, other perinatal environmental factors that affect behavior (e.g. diet and stress) also elicit inflammatory responses. Understanding the interplay between perinatal environment and inflammation on brain development is required to identify the mechanisms through which perinatal inflammation affect brain function in the adult animal. Evidence for the role of the peripheral immune system and glia on perinatal programming of behavior is discussed in this review, along with recent evidence for the role of epigenetic mechanisms affecting gene expression in the brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

Peripheral Organs of Dengue Fatal Cases Present Strong Pro-Inflammatory Response with Participation of IFN-Gamma-, TNF-Alpha- and RANTES-Producing Cells.

PubMed

Póvoa, Tiago F; Oliveira, Edson R A; Basílio-de-Oliveira, Carlos A; Nuovo, Gerard J; Chagas, Vera L A; Salomão, Natália G; Mota, Ester M; Paes, Marciano V

2016-01-01

Dengue disease is an acute viral illness caused by dengue virus (DENV) that can progress to hemorrhagic stages leading to about 20000 deaths every year worldwide. Despite many clinical investigations regarding dengue, the immunopathogenic process by which infected patients evolve to the severe forms is not fully understood. Apart from differences in virulence and the antibody cross reactivity that can potentially augment virus replication, imbalanced cellular immunity is also seen as a major concern in the establishment of severe dengue. In this context, the investigation of cellular immunity and its products in dengue fatal cases may provide valuable data to help revealing dengue immunopathogenesis. Here, based in four dengue fatal cases infected by the serotype 3 in Brazil, different peripheral organs (livers, lungs and kidneys) were studied to evaluate the presence of cell infiltrates and the patterns of local cytokine response. The overall scenario of the studied cases revealed a considerable systemic involvement of infection with mononuclear cells targeted to all of the evaluated organs, as measured by immunohistochemistry (IHC). Quantification of cytokine-expressing cells in peripheral tissues was also performed to characterize the ongoing inflammatory process by the severe stage of the disease. Increased levels of IFN-γ- and TNF-α-expressing cells in liver, lung and kidney samples of post-mortem subjects evidenced a strong pro-inflammatory induction in these tissues. The presence of increased RANTES-producing cell numbers in all analyzed organs suggested a possible link between the clinical status and altered vascular permeability. Co-staining of DENV RNA and IFN-γ or TNF-α using in situ hibridization and IHC confirmed the virus-specific trigger of the pro-inflammatory response. Taken together, this work provided additional evidences that corroborated with the traditional theories regarding the "cytokine storm" and the occurrence of uneven cellular immunity in response to DENV as major reasons for progress to severe disease.

Unipedal stance testing in the assessment of peripheral neuropathy.

PubMed

Hurvitz, E A; Richardson, J K; Werner, R A

2001-02-01

To define further the relation between unipedal stance testing and peripheral neuropathy. Prospective cohort. Electroneuromyography laboratory of a Veterans Affairs medical center and a university hospital. Ninety-two patients referred for lower extremity electrodiagnostic studies. A standardized history and physical examination designed to detect peripheral neuropathy, 3 trials of unipedal stance, and electrodiagnostic studies. Peripheral neuropathy was identified by electrodiagnostic testing in 32%. These subjects had a significantly shorter (p <.001) unipedal stance time (15.7s, longest of 3 trials) than the patients without peripheral neuropathy (37.1s). Abnormal unipedal stance time (<45s) identified peripheral neuropathy with a sensitivity of 83% and a specificity of 71%, whereas a normal unipedal stance time had a negative predictive value of 90%. Abnormal unipedal stance time was associated with an increased risk of having peripheral neuropathy on univariate analysis (odds ratio = 8.8, 95% confidence interval = 2.5--31), and was the only significant predictor of peripheral neuropathy in the regression model. Aspects of the neurologic examination did not add to the regression model compared with abnormal unipedal stance time. Unipedal stance testing is useful in the clinical setting both to identify and to exclude the presence of peripheral neuropathy.

Are visual peripheries forever young?

PubMed

Burnat, Kalina

2015-01-01

The paper presents a concept of lifelong plasticity of peripheral vision. Central vision processing is accepted as critical and irreplaceable for normal perception in humans. While peripheral processing chiefly carries information about motion stimuli features and redirects foveal attention to new objects, it can also take over functions typical for central vision. Here I review the data showing the plasticity of peripheral vision found in functional, developmental, and comparative studies. Even though it is well established that afferent projections from central and peripheral retinal regions are not established simultaneously during early postnatal life, central vision is commonly used as a general model of development of the visual system. Based on clinical studies and visually deprived animal models, I describe how central and peripheral visual field representations separately rely on early visual experience. Peripheral visual processing (motion) is more affected by binocular visual deprivation than central visual processing (spatial resolution). In addition, our own experimental findings show the possible recruitment of coarse peripheral vision for fine spatial analysis. Accordingly, I hypothesize that the balance between central and peripheral visual processing, established in the course of development, is susceptible to plastic adaptations during the entire life span, with peripheral vision capable of taking over central processing.

Peripheral vascular dysfunction in migraine: a review

PubMed Central

2013-01-01

Numerous studies have indicated an increased risk of vascular disease among migraineurs. Alterations in endothelial and arterial function, which predispose to atherosclerosis and cardiovascular diseases, have been suggested as an important link between migraine and vascular disease. However, the available evidence is inconsistent. We aimed to review and summarize the published evidence about the peripheral vascular dysfunction of migraineurs. We systematically searched in BIOSIS, the Cochrane database, Embase, Google scholar, ISI Web of Science, and Medline to identify articles, published up to April 2013, evaluating the endothelial and arterial function of migraineurs. Several lines of evidence for vascular dysfunction were reported in migraineurs. Findings regarding endothelial function are particularly controversial since studies variously indicated the presence of endothelial dysfunction in migraineurs, the absence of any difference in endothelial function between migraineurs and non-migraineurs, and even an enhanced endothelial function in migraineurs. Reports on arterial function are more consistent and suggest that functional properties of large arteries are altered in migraineurs. Peripheral vascular function, particularly arterial function, is a promising non-invasive indicator of the vascular health of subjects with migraine. However, further targeted research is needed to understand whether altered arterial function explains the increased risk of vascular disease among patients with migraine. PMID:24083826

Atherectomy for peripheral arterial disease.

PubMed

Ambler, Graeme K; Radwan, Rami; Hayes, Paul D; Twine, Christopher P

2014-03-17

Symptomatic peripheral arterial disease may be treated by a number of options including exercise therapy, angioplasty, stenting and bypass surgery. Atherectomy is an alternative technique where atheroma is excised by a rotating cutting blade. The objective of this review was to analyse randomised controlled trials comparing atherectomy against any established treatment for peripheral arterial disease in order to evaluate the effectiveness of atherectomy. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched November 2013) and CENTRAL (2013, Issue 10). Trials databases were searched for details of ongoing or unpublished studies. Randomised controlled trials (RCTs) comparing atherectomy and other established treatments were selected for inclusion. All participants had symptomatic peripheral arterial disease with either claudication or critical limb ischaemia and evidence of lower limb arterial disease. Two review authors (GA and CT) screened studies for inclusion, extracted data and assessed the quality of the trials. Any disagreements were resolved through discussion. Four trials were included with a total of 220 participants (118 treated with atherectomy, 102 treated with balloon angioplasty) and 259 treated vessels (129 treated with atherectomy, 130 treated with balloon angioplasty). All studies compared atherectomy with angioplasty. No study was properly powered or assessors blinded to the procedures and there was a high risk of selection, attrition, detection and reporting biases.The estimated risk of success was similar between the treatment modalities although the confidence interval (CI) was compatible with small benefits of either treatment for the initial procedural success rate (Mantel-Haenszel risk ratio (RR) 0.92, 95% CI 0.44 to 1.91, P = 0.82), patency at six months (Mantel-Haenszel RR 0.92, 95% CI 0.51 to 1.66, P = 0.79) and patency at 12 months (Mantel-Haenszel RR 1.17, 95% CI 0.72 to 1.90, P = 0.53) following the procedure. The reduction in all-cause mortality with atherectomy was most likely due to an unexpectedly high mortality in the balloon angioplasty group in one of the two trials that reported mortality (Mantel-Haenszel RR 0.24, 95% CI 0.06 to 0.91, P = 0.04). Cardiovascular events were not reported in any study. There was a reduction in the rate of bailout stenting following atherectomy (Mantel-Haenszel RR 0.45, 95% CI 0.24 to 0.84, P = 0.01), and balloon inflation pressures were lower following atherectomy (mean difference -2.73 mmHg, 95% CI -3.48 to -1.98, P < 0.00001). Complications such as embolisation and vessel dissection were reported in two trials indicating more embolisations in the atherectomy group and more vessel dissections in the angioplasty group, but the data could not be pooled. From the limited data available, there was no clear evidence of different rates of adverse events between the atherectomy and balloon angioplasty groups for target vessel revascularisation and above-knee amputation. Quality of life and clinical and symptomatic outcomes such as walking distance or symptom relief were not reported in the studies. This review has identified poor quality evidence to support atherectomy as an alternative to balloon angioplasty in maintaining primary patency at any time interval. There was no evidence for superiority of atherectomy over angioplasty on any outcome, and distal embolisation was not reported in all trials of atherectomy. Properly powered trials are recommended.

Gadolinium deposition disease: Initial description of a disease that has been around for a while.

PubMed

Semelka, Richard C; Ramalho, Joana; Vakharia, Ami; AlObaidy, Mamdoh; Burke, Lauren M; Jay, Michael; Ramalho, Miguel

2016-12-01

To describe the clinical manifestations of presumed gadolinium toxicity in patients with normal renal function. Participants were recruited from two online gadolinium toxicity support groups. The survey was anonymous and individuals were instructed to respond to the survey only if they had evidence of normal renal function, evidence of gadolinium in their system beyond 30days of this MRI, and no pre-existent clinical symptoms and/or signs of this type. 42 subjects responded to the survey (age: 28-69, mean 49.1±22.4years). The most common findings were: central pain (n=15), peripheral pain (n=26), headache (n=28), and bone pain (n=26). Only subjects with distal leg and arm distribution described skin thickening (n=22). Clouded mentation and headache were the symptoms described as persistent beyond 3months in 29 subjects. Residual disease was present in all patients. Twenty-eight patients described symptoms following administration of one brand of Gadolinium-Based Contrast Agent (GBCA), 21 after a single GBCA administration and 7 after multiple GBCA administrations, including: gadopentetate dimeglumine, n=9; gadodiamide, n=4; gadoversetamide, n=4; gadobenate dimeglumine, n=4; gadobutrol, n=1; gadoteridol, n=2; and unknown, n=4. Gadolinium toxicity appears to arise following GBCA administration, which appears to contain clinical features seen in Nephrogenic Systemic Fibrosis, but also features not observed in that condition. Copyright © 2016 Elsevier Inc. All rights reserved.

Raman spectroscopic detection of peripheral nerves towards nerve-sparing surgery

NASA Astrophysics Data System (ADS)

Minamikawa, Takeo; Harada, Yoshinori; Takamatsu, Tetsuro

2017-02-01

The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery, namely nerve-sparing surgery, is now promising technique to avoid functional deficits of the limbs and organs following surgery as an aspect of the improvement of quality of life of patients. Detection of peripheral nerves including myelinated and unmyelinated nerves is required for the nerve-sparing surgery; however, conventional nerve identification scheme is sometimes difficult to identify peripheral nerves due to similarity of shape and color to non-nerve tissues or its limited application to only motor peripheral nerves. To overcome these issues, we proposed a label-free detection technique of peripheral nerves by means of Raman spectroscopy. We found several fingerprints of peripheral myelinated and unmyelinated nerves by employing a modified principal component analysis of typical spectra including myelinated nerve, unmyelinated nerve, and adjacent tissues. We finally realized the sensitivity of 94.2% and the selectivity of 92.0% for peripheral nerves including myelinated and unmyelinated nerves against adjacent tissues. Although further development of an intraoperative Raman spectroscopy system is required for clinical use, our proposed approach will serve as a unique and powerful tool for peripheral nerve detection for nerve-sparing surgery in the future.

Fragmentation of care threatens patient safety in peripheral vascular catheter management in acute care--a qualitative study.

PubMed

Castro-Sánchez, Enrique; Charani, Esmita; Drumright, Lydia N; Sevdalis, Nick; Shah, Nisha; Holmes, Alison H

2014-01-01

The use of peripheral vascular catheters (PVCs) is an extremely common and necessary clinical intervention, but inappropriate PVC care poses a major patient safety risk in terms of infection. Quality improvement initiatives have been proposed to reduce the likelihood of adverse events, but a lack of understanding about factors that influence behaviours of healthcare professionals limits the efficacy of such interventions. We undertook qualitative interviews with clinical staff from a large group of hospitals in order to understand influences on PVC care behaviors and subsequent patient safety. Ten doctors, ten clinical pharmacists, 18 nurses and one midwife at a National Health Service hospital group in London (United Kingdom) were interviewed between December 2010 and July 2011 using qualitative methods. Responses were analysed using a thematic framework. FOUR KEY THEMES EMERGED: 1) Fragmentation of management and care, demonstrated with a lack of general overview and insufficient knowledge about expected standards of care or responsibility of different professionals; 2) feelings of resentment and frustration as a result of tensions in the workplace, due to the ambiguity about professional responsibilities; 3) disregard for existing hospital policy due to perceptions of flaws in the evidence used to support it; and 4) low-risk perception for the impact of PVC use on patient safety. Fragmentation of practice resulted in ill-defined responsibilities and interdisciplinary resentment, which coupled with a generally low perception of risk of catheter use, appeared to result in lack of maintaining policy PVC standards which could reduced patient safety. Resolution of these issues through clearly defining handover practice, teaching interdisciplinary duties and increasing awareness of PVC risks could result in preventing thousands of BSIs and other PVC-related infections annually.

Alcohol and high fat induced chronic pancreatitis: TRPV4 antagonist reduces hypersensitivity.

PubMed

Zhang, L P; Kline, R H; Deevska, G; Ma, F; Nikolova-Karakashian, M; Westlund, K N

2015-12-17

The pathogenesis of pain in chronic pancreatitis is poorly understood, and its treatment can be a major clinical challenge. Surgical and other invasive methods have variable outcomes that can be unsatisfactory. Therefore, there is a great need for further discovery of the pathogenesis of pancreatitis pain and new therapeutic targets. Human and animal studies indicate a critical role for oxidative stress and activation of transient receptor potential (TRP) cation channel subfamily members TRPV1 and TRPA1 on pancreatic nociceptors in sensitization mechanisms that result in pain. However, the in vivo role of transient receptor potential cation channel subfamily V member 4 (TRPV4) in chronic pancreatitis needs further evaluation. The present study characterized a rat alcohol/high fat diet (AHF)-induced chronic pancreatitis model with hypersensitivity, fibrotic pathology, and fat vacuolization consistent with the clinical syndrome. The rats with AHF-induced pancreatitis develop referred visceral pain-like behaviors, i.e. decreased hindpaw mechanical thresholds and shortened abdominal and hindpaw withdrawal latency to heat. In this study, oxidative stress was characterized as well as the role of TRPV4 in chronic visceral hypersensitivity. Lipid peroxidase and oxidative stress were indicated by increased plasma thiobarbituric acid reactive substances (TBARS) and diminished pancreatic manganese superoxide dismutase (MnSOD). The secondary sensitization associated with AHF-induced pancreatitis was effectively alleviated by the TRPV4 antagonist, HC 067047. Similarity of the results to those with the peripherally restricted μ-opiate receptor agonist, loperamide, suggested TRPV4 channel activated peripheral sensitization. This study using a reliable model that provides pre-clinical correlates of human chronic pancreatitis provides further evidence that TRPV4 channel is a potential therapeutic target for treatment of pancreatitis pain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Genetic and molecular basis of diabetic foot ulcers: Clinical review.

PubMed

Jhamb, Shaurya; Vangaveti, Venkat N; Malabu, Usman H

2016-11-01

Diabetic Foot Ulcers (DFUs) are major complications associated with diabetes and often correlate with peripheral neuropathy, trauma and peripheral vascular disease. It is necessary to understand the molecular and genetic basis of diabetic foot ulcers in order to tailor patient centred care towards particular patient groups. This review aimed to evaluate whether current literature was indicative of an underlying molecular and genetic basis for DFUs and to discuss clinical applications. From a molecular perspective, wound healing is a process that transpires following breach of the skin barrier and is usually mediated by growth factors and cytokines released by specialised cells activated by the immune response, including fibroblasts, endothelial cells, phagocytes, platelets and keratinocytes. Growth factors and cytokines are fundamental in the organisation of the molecular processes involved in making cutaneous wound healing possible. There is a significant role for single nucleotide polymorphism (SNPs) in the fluctuation of these growth factors and cytokines in DFUs. Furthermore, recent evidence suggests a key role for epigenetic mechanisms such as DNA methylation from long standing hyperglycemia and non-coding RNAs in the complex interplay between genes and the environment. Genetic factors and ethnicity can also play a significant role in the development of diabetic neuropathy leading to DFUs. Clinically, interventions which have improved outcomes for people with DFUs or those at risk of DFUs include some systemic therapeutic drug interventions which improve microvascular blood flow, surgical interventions, human growth factors, and hyperbaric oxygen therapy, negative pressure wound therapy, skin replacement or shockwave therapy and the use of topical treatments. Future treatment modalities including stem cell and gene therapies are promising in the therapeutic approach to prevent the progression of chronic diabetic complications. Copyright © 2016 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Evaluation of acupuncture in the management of chemotherapy-induced peripheral neuropathy.

PubMed

Donald, Graeme K; Tobin, Irene; Stringer, Jacqui

2011-09-01

To clinically evaluate the effectiveness of acupuncture when used in the management of chemotherapy-induced peripheral neuropathy (PN). During cancer treatment, certain chemotherapies can cause varying degrees of PN. Patients' quality of life can be seriously impaired through loss of sensation, pain or mobility problems. Conventional medications routinely used to manage neuropathic symptoms have poor side-effect profiles and there is little or no evidence justifying their use to treat chemotherapy-related neurotoxicities. There are studies suggesting that acupuncture may be an effective therapy in treating PN across a number of different aetiologies. Design A retrospective service evaluation. Patients (n=18) were referred for acupuncture by the medical staff and/ornurse specialists or they self-referred for treatment. A course of six weekly acupuncture sessions was offered to them, and their details were recorded on an evaluation form prior to session one. Points were selected by acupuncturists, based on patient presentation, and needles remained in situ for 30-45 min. Treatments took place in outpatient clinics, chemotherapy day case ward or a drop-in clinic based in a physiotherapy gym. The evaluation form was completed at the end of session 6 by a therapist who had not been involved in patient care. 82% (n=14) of patients reported an improvement in symptoms following their course of acupuncture; one patient with advanced disease died during the 6 weeks. Some patients derived additional benefits from the treatment including a reduction in analgesic use and improved sleeping patterns. The most common acupoints used were SP6 (n=18), ST36 (n=18) and LV3 (n=14). Although these results are encouraging, they are uncontrolled. They suggest that acupuncture could be an option for these patients and controlled trials using validated patient-reported outcome measures are justified.

The fundamental role of subcellular topography in peripheral nerve repair therapies.

PubMed

Spivey, Eric C; Khaing, Zin Z; Shear, Jason B; Schmidt, Christine E

2012-06-01

Clinical evidence suggests that nano- and microtopography incorporated into scaffolds does not merely improve peripheral nerve regeneration, but is in fact a prerequisite for meaningful restoration of nerve function. Although the biological mechanisms involved are not fully understood, grafts incorporating physical guides that mimic microscopic nerve tissue features (e.g., basal laminae) appear to provide a significant advantage over grafts that rely on purely chemical or macroscopic similarities to nerve tissue. Investigators consistently demonstrate the fundamental importance of nano- and micro-scale physical features for appropriate cell response in a wide range of biological scenarios. Additionally, recent in vivo research demonstrates that nerve regeneration scaffolds with cell-scale physical features are more effective than those that rely only on chemical or macro-scale features. Physical guidance at the cell-scale is especially important for long (>20 mm) nerve defects, for which the only reliable treatment is the autologous nerve graft. The lack of other available options exposes a clear need for the application of nano- and microfabrication techniques that will allow the next generation of engineered nerve guides to more closely mimic native tissue at those scales. This review examines current research to determine what elements of cell-scale topography in experimental scaffolds are most effective at stimulating functional recovery, and then presents an overview of fabrication techniques that could potentially improve future treatment paradigms. Relative advantages and disadvantages of these techniques are discussed, with respect to both clinical adaptation and likely effectiveness. Our intent is to more clearly delineate the remaining obstacles in the development of a next generation nerve guide, particularly for long defects, and offer new perspectives on steering current technologies towards clinically viable solutions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Radiological characteristics, histological features and clinical outcomes of lung cancer patients with coexistent idiopathic pulmonary fibrosis.

PubMed

Khan, K A; Kennedy, M P; Moore, E; Crush, L; Prendeville, S; Maher, M M; Burke, L; Henry, M T

2015-02-01

Despite advances in diagnosis and management, the outcomes for both lung cancer and idiopathic pulmonary fibrosis (IPF) are still unfavourable. The pathophysiology and outcomes for patients with concomitant lung cancer and IPF remains unclear. A retrospective analysis was performed of all patients presenting with concomitant IPF and lung cancer to our centre over a 3-year period. Patients with connective tissue disease, asbestos exposure, sarcoidosis, previous thoracic radiation, radiological evidence of fibrosis but no histological confirmation of lung cancer, or the use of medications known to cause pulmonary fibrosis were excluded. We describe clinical, radiological and pathological characteristics of this group. We also report the response to standardized lung cancer therapy in this cohort. Of 637 lung cancer patients, 34 were identified with concomitant IPF (5.3 %) and all were smokers. 85 % had non-small cell lung cancer, 41 % were squamous cell cancers. The majority of tumours were located in the lower lobes, peripheral and present in an area of honeycombing. Despite the fact that approximately 2/3rds of the patients had localised or locally advanced lung cancer, the outcome of therapy for lung cancer was extremely poor regardless of tumour stage or severity of IPF. At our centre, 1/20 patients with lung cancer have concomitant IPF. The majority of these tumours are small in size, peripheral in location and squamous cell carcinoma; in an area of honey combing. The outcome for concomitant lung cancer and IPF regardless of stage or therapy is poor.

Serum interleukin-6 is related to lower cognitive functioning in elderly patients with major depression.

PubMed

Ali, Nehad Samir; Hashem, Abdel Hamid Hashem; Hassan, Akmal Mostafa; Saleh, Alia Adel; El-Baz, Heba Nabil

2018-05-01

There is an increased evidence of an association between inflammatory mediators, particularly serum IL-6, depression and cognitive impairment in the elderly. This study aims at exploring the relation of peripheral IL-6 to cognitive functions in elderly patients with major depressive disorder (MDD). (1) Assessment of serum IL-6 levels and cognitive functions in elderly patients suffering from major depression and comparing them to healthy age-matched control subjects; (2) correlation between serum IL-6 levels and clinical characteristics of depression and cognitive functions in these patients. The study is an observational, case-control study. It consisted of 80 subjects, 40 with the diagnosis of MDD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR) with early onset (first episode before the age of 60) and 40 community-dwelling subjects. They were subjected to the Structured Clinical Interview according to DSM-IV, Montreal Cognitive Assessment, Montgomery Asberg Depression Rating Scale, and serum IL-6 assay using ELISA. In the depression group, subjects had lower scores in cognitive testing, than the control group (p = 0.001). Serum IL-6 was found to have a negative correlation with cognitive testing in these patients even after controlling for the severity of depressive status and Body Mass Index (BMI) (p = 0.025). MDD in elderly subjects is associated with decline in cognitive functions that may be related to peripheral IL-6 levels.

Kisspeptin and Metabolism: The Brain and Beyond.

PubMed

Dudek, Monika; Ziarniak, Kamil; Sliwowska, Joanna H

2018-01-01

Apart from the well-established role of kisspeptin (Kp) in the regulation of reproductive functions, recent data described its action in the control of metabolism. Of particular interest for the review is the population of Kp neurons localized in the arcuate nucleus (ARC) of the hypothalamus, the site of the brain where reproductive and metabolic cross talk occurs. However, within the hypothalamus Kp does not work alone, but rather interacts with other neuropeptides, e.g., neurokinin B, dynorphin A, proopiomelanocortin, the cocaine- and amphetamine-regulated transcript, agouti-related peptide, and neuropeptide Y. Beyond the brain, Kp is expressed in peripheral tissues involved in metabolic functions. In this review, we will mainly focus on the local action of this peptide in peripheral organs such as the pancreas, liver, and the adipose tissue. We will concentrate on dysregulation of the Kp system in cases of metabolic imbalance, e.g., obesity and diabetes. Importantly, these patients besides metabolic health problems often suffer from disruptions of the reproductive system, manifested by abnormalities in menstrual cycles, premature child birth, miscarriages in women, decreased testosterone levels and spermatogenesis in men, hypogonadism, and infertility. We will review the evidence from animal models and clinical data indicating that Kp could serve as a promising agent with clinical applications in regulation of reproductive problems in individuals with obesity and diabetes. Finally, emerging data indicate a role of Kp in regulation of insulin secretion, potentially leading to development of further therapeutic uses of this peptide to treat metabolic problems in patients with these lifestyle diseases.

Symptomatic Treatment of Cough Among Adult Patients With Lung Cancer: CHEST Guideline and Expert Panel Report.

PubMed

Molassiotis, Alex; Smith, Jaclyn A; Mazzone, Peter; Blackhall, Fiona; Irwin, Richard S

2017-04-01

Cough among patients with lung cancer is a common but often undertreated symptom. We used a 2015 Cochrane systematic review, among other sources of evidence, to update the recommendations and suggestions of the American College of Chest Physicians (CHEST) 2006 guideline on this topic. The CHEST methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework were used. The Expert Cough Panel based their recommendations on data from the Cochrane systematic review on the topic, uncontrolled studies, case studies, and the clinical context. Final grading was reached by consensus according to the Delphi method. The Cochrane systematic review identified 17 trials of primarily low-quality evidence. Such evidence was related to both nonpharmacologic (cough suppression) and pharmacologic (demulcents, opioids, peripherally acting antitussives, or local anesthetics) treatments, as well as endobronchial brachytherapy. Compared with the 2006 CHEST Cough Guideline, the current recommendations and suggestions are more specific and follow a step-up approach to the management of cough among patients with lung cancer, acknowledging the low-quality evidence in the field and the urgent need to develop more effective, evidence-based interventions through high-quality research. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Study to determine the clinical significance of HEmolysis During Orbital AtheRectomy (CLEAR study).

PubMed

Staniloae, Cezar S; Korabathina, Ravikiran; Lane, Thomas A; Dattilo, Raymond; Church, Kevin J; Mody, Kanika P; Mayeda, Guy S

2011-02-01

To evaluate the incidence of clinically evident hemolysis associated with orbital atherectomy used to treat severe peripheral artery disease. The observational CLEAR study enrolled 31 subjects (16 men; mean age 71 ± 10 years, range 44-92) with claudication (58.1%) or critical limb ischemia (38.7%) who underwent orbital atherectomy with the Diamondback 360 system at 4 US centers. The 42 lesions in 31 limbs were located in the superficial femoral (n = 19, 45.2%), popliteal (n = 8, 19.0%), and tibial arteries (n = 15, 35.8%). The majority of lesions (34, 81.0%) were de novo; moderate or severe calcification was identified in 90.5% of cases. Lesion and procedural parameters were analyzed at a core laboratory. Blood samples were collected during and post procedure and analyzed for markers of hemolysis. The primary endpoint was the occurrence of clinically significant hemolysis. The secondary endpoints included the occurrence of any clinical symptoms/signs potentially related to hemolysis. Statistical analysis was performed to identify predictors for hemolysis. Laboratory evidence of hemolysis was seen in 11 (35.5%) subjects. No one met the clinical event criteria, and so the primary endpoint of the study was not reached. The secondary endpoints were hypertensive crisis (1, 3.2%) and transient hemoglobinuria (3, 9.7%). Lower glomerular filtration rates, calcified plaque, long atherectomy runs, and solid crown selection were independent predictors of hemolysis. There was no clinically significant hemolysis after orbital atherectomy. The results of this study will enable users to predict conditions that predispose to high levels of red cell hemolysis following orbital atherectomy and to take appropriate measures to limit its occurrence.

Expression of CD34 and CD68 in peripheral giant cell granuloma and central giant cell granuloma: An immunohistochemical analysis

PubMed Central

VK, Varsha; Hallikeri, Kaveri; Girish, HC; Murgod, Sanjay

2014-01-01

Background: Central and Peripheral giant cell granulomas of jaws are uncommon, benign, reactive disorders that are characterized by the presence of numerous multinucleated giant cells and mononuclear cells within a stroma. The origin of the multinucleated giant cells is controversial; probably originating from fusion of histiocytes, endothelial cells and fibroblasts. Objective: To assess the expression of CD34 and CD68 in central and peripheral giant cell granulomas to understand the origin of these multinucleated giant cells. Materials and Methods: Twenty cases of Central and Peripheral giant cell granulomas were evaluated immunohistochemically for CD34 and CD68 proteins expression. Results: Immunopositivity for CD34 was seen only in cytoplasm of endothelial cells of blood vessels; whereas, consistent cytoplasmic immunopositivity for CD68 was seen in few stromal cells. Statistical significance was seen in mean number of multinucleated giant cells, mean number of nuclei in multinucleated giant cells, CD68 expression and ratio of macrophages to multinucleated giant cells among two lesions. Conclusion: Although the central giant cell granulomas share some clinical and histopathological similarities with peripheral giant cell granulomas, differences in mean number of nuclei in multinucleated giant cells and CD68 immunoreactivity may underlie the distinct clinical behavior. PMID:25948986

Longitudinal peripheral blood transcriptional analysis of a patient with severe Ebola virus disease

PubMed Central

Kash, John C.; Walters, Kathie-Anne; Kindrachuk, Jason; Baxter, David; Scherler, Kelsey; Janosko, Krisztina B.; Adams, Rick D.; Herbert, Andrew S.; James, Rebekah M.; Stonier, Spencer W.; Memoli, Matthew J.; Dye, John M.; Davey, Richard T.; Chertow, Daniel S.; Taubenberger, Jeffery K.

2017-01-01

The 2013–2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was unprecedented in the number of documented cases, but there have been few published reports on immune responses in clinical cases and their relationships with the course of illness and severity of Ebola virus disease. Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia, fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although experimental treatments are in development, there are no current U.S. Food and Drug Administration–approved vaccines or therapies. We report a detailed study of host gene expression as measured by microarray in daily peripheral blood samples collected from a patient with severe Ebola virus disease. This individual was provided with supportive care without experimental therapies at the National Institutes of Health Clinical Center from before onset of critical illness to recovery. Pearson analysis of daily gene expression signatures revealed marked gene expression changes in peripheral blood leukocytes that correlated with changes in serum and peripheral blood leukocytes, viral load, antibody responses, coagulopathy, multiple organ dysfunction, and then recovery. This study revealed marked shifts in immune and antiviral responses that preceded changes in medical condition, indicating that clearance of replicating Ebola virus from peripheral blood leukocytes is likely important for systemic viral clearance. PMID:28404864

Non-invasive peripheral nerve stimulation via focused ultrasound in vivo

NASA Astrophysics Data System (ADS)

Downs, Matthew E.; Lee, Stephen A.; Yang, Georgiana; Kim, Seaok; Wang, Qi; Konofagou, Elisa E.

2018-02-01

Focused ultrasound (FUS) has been employed on a wide range of clinical applications to safely and non-invasively achieve desired effects that have previously required invasive and lengthy procedures with conventional methods. Conventional electrical neuromodulation therapies that are applied to the peripheral nervous system (PNS) are invasive and/or non-specific. Recently, focused ultrasound has demonstrated the ability to modulate the central nervous system and ex vivo peripheral neurons. Here, for the first time, noninvasive stimulation of the sciatic nerve eliciting a physiological response in vivo is demonstrated with FUS. FUS was applied on the sciatic nerve in mice with simultaneous electromyography (EMG) on the tibialis anterior muscle. EMG signals were detected during or directly after ultrasound stimulation along with observable muscle contraction of the hind limb. Transecting the sciatic nerve downstream of FUS stimulation eliminated EMG activity during FUS stimulation. Peak-to-peak EMG response amplitudes and latency were found to be comparable to conventional electrical stimulation methods. Histology along with behavioral and thermal testing did not indicate damage to the nerve or surrounding regions. The findings presented herein demonstrate that FUS can serve as a targeted, safe and non-invasive alternative to conventional peripheral nervous system stimulation to treat peripheral neuropathic diseases in the clinic.

Central and Peripheral factors contributing to Obstructive Sleep Apneas

PubMed Central

Ramirez, Jan-Marino; Garcia, Alfredo J.; Anderson, Tatiana M.; Koschnitzky, Jenna E.; Peng, Ying-Jie; Kumar, Ganesh; Prabhakar, Nanduri

2013-01-01

Apnea, the cessation of breathing, is a common physiological and pathophysiological phenomenon with many basic scientific and clinical implications. Among the different forms of apnea, obstructive sleep apnea (OSA) is clinically the most prominent manifestation. OSA is characterized by repetitive airway occlusions that are typically associated with peripheral airway obstructions. However, it would be a gross oversimplification to conclude that OSA is caused by peripheral obstructions. OSA is the result of a dynamic interplay between chemo- and mechanosensory reflexes, neuromodulation, behavioral state and the differential activation of the central respiratory network and its motor outputs. This interplay has numerous neuronal and cardiovascular consequences that are initially adaptive but in the long-term become major contributors to the morbidity and mortality associated with OSA. However, not only OSA, but all forms of apnea have multiple, and partly overlapping mechanisms. In all cases the underlying mechanisms are neither “exclusively peripheral” nor “exclusively central” in origin. While the emphasis has long been on the role of peripheral reflex pathways in the case of OSA, and central mechanisms in the case of central apneas, we are learning that such a separation is inconsistent with the integration of these mechanisms in all cases of apneas. This review discusses the complex interplay of peripheral and central nervous components that characterizes the cessation of breathing. PMID:23770311

Shah-Waardenburg syndrome and PCWH associated with SOX10 mutations: a case report and review of the literature.

PubMed

Verheij, Johanna B G M; Sival, Deborah A; van der Hoeven, Johannes H; Vos, Yvonne J; Meiners, Linda C; Brouwer, Oebele F; van Essen, Anthonie J

2006-01-01

Shah-Waardenburg syndrome is a rare congenital disorder with variable clinical expression, characterised by aganglionosis of the rectosigmoïd (Hirschsprung disease), and abnormal melanocyte migration, resulting in pigmentary abnormalities and sensorineural deafness (Waardenburg syndrome). Mutations in the EDN, EDNRB and SOX10 genes can be found in patients with this syndrome. SOX10 mutations are specifically associated with a more severe phenotype called PCWH: peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease. Neuronal expression of SOX10 occurs in neural crest cells during early embryonic development and in glial cells of the peripheral and central nervous systems during late embryonic development and in adults. We present a 4-year-old girl with the PCWH phenotype associated with a de novo nonsense mutation (S384X) in SOX10. Main clinical features were mental retardation, peripheral neuropathy, deafness, Hirschsprung disease, distal arthrogryposis, white hairlock, and growth retardation. She presented with hypotonia, developmental delay, reduced peripheral nerve conduction velocities, and radiologically assessed central hypomyelination. Subsequently, the formation of abnormal myelin within the central and peripheral nervous system was functionally and radiologically assessed. Children presenting with features of Waardenburg syndrome and neurological dysfunction should be tested for mutations in the SOX10 gene to enable diagnosis and counselling.

Liposomal Bupivacaine Does Not Reduce Inpatient Opioid Prescription or Related Complications after Knee Arthroplasty: A Database Analysis.

PubMed

Pichler, Lukas; Poeran, Jashvant; Zubizarreta, Nicole; Cozowicz, Crispiana; Sun, Eric C; Mazumdar, Madhu; Memtsoudis, Stavros G

2018-05-21

Although some trials suggest benefits of liposomal bupivacaine, data on real-world use and effectiveness is lacking. This study analyzed the impact of liposomal bupivacaine use (regardless of administration route) on inpatient opioid prescription, resource utilization, and opioid-related complications among patients undergoing total knee arthroplasties with a peripheral nerve block. It was hypothesized that liposomal bupivacaine has limited clinical influence on the studied outcomes. The study included data on 88,830 total knee arthroplasties performed with a peripheral nerve block (Premier Healthcare Database 2013 to 2016). Multilevel multivariable regressions measured associations between use of liposomal bupivacaine and (1) inpatient opioid prescription (extracted from billing) and (2) length of stay, cost of hospitalization, as well as opioid-related complications. To reflect the difference between statistical and clinical significance, a relative change of -15% in outcomes was assumed to be clinically important. Overall, liposomal bupivacaine was used in 21.2% (n = 18,817) of patients that underwent a total knee arthroplasty with a peripheral nerve block. Liposomal bupivacaine use was not associated with a clinically meaningful reduction in inpatient opioid prescription (group median, 253 mg of oral morphine equivalents, adjusted effect -9.3% CI -11.1%, -7.5%; P < 0.0001) and length of stay (group median, 3 days, adjusted effect -8.8% CI -10.1%, -7.5%; P < 0.0001) with no effect on cost of hospitalization. Most importantly, liposomal bupivacaine use was not associated with decreased odds for opioid-related complications. Liposomal bupivacaine was not associated with a clinically relevant improvement in inpatient opioid prescription, resource utilization, or opioid-related complications in patients who received modern pain management including a peripheral nerve block.

What is the Best Strategy on Detection of Cornea Neuropathy in People with Diabetes? Recent Advances in Potential Measurements.

PubMed

Lv, Ying; Zhao, Shaozhen

2018-03-26

There are well-acknowledged clinical or pre-clinical measurements concerning diabetic peripheral neuropathy(DPN). The current gold standard for diagnosis of diabetic peripheral neuropathy is nerve conduction suitable for detecting large nerve fiber function[1] and intraepidermal nerve fiber density assessment for small fiber damage evaluation[2]. The lack of a sensitive, non-invasive, and repeatable endpoint to measure changes in small nerve fibers is a major factor holding back clinical trials for the treatment of diabetic peripheral neuropathy. As cornea is the most densely innerved tissue, assessing corneal nerves' structure and function will be promising to predict and assess the degree of DPN [3]. In the diabetic micro-environment, damaged corneal nerves lead to decreased corneal sensitivity, both of which resulting in abnormal tear function. According to this theory, the measurements of nerve structure, corneal sensitivity, tear secretion and tear components, to some extent, can reveal and assess the state of corneal neuropathy. This review focuses on summarizing the knowledge of the latest detective methods of diabetic corneal neuropathy, popular in use or possible to further in study and be applied into clinical practice. Copyright © 2018 Elsevier B.V. All rights reserved.

Peripheral biomarkers revisited: integrative profiling of peripheral samples for psychiatric research.

PubMed

Hayashi-Takagi, Akiko; Vawter, Marquis P; Iwamoto, Kazuya

2014-06-15

Peripheral samples, such as blood and skin, have been used for decades in psychiatric research as surrogates for central nervous system samples. Although the validity of the data obtained from peripheral samples has been questioned and other state-of-the-art techniques, such as human brain imaging, genomics, and induced pluripotent stem cells, seem to reduce the value of peripheral cells, accumulating evidence has suggested that revisiting peripheral samples is worthwhile. Here, we re-evaluate the utility of peripheral samples and argue that establishing an understanding of the common signaling and biological processes in the brain and peripheral samples is required for the validity of such models. First, we present an overview of the available types of peripheral cells and describe their advantages and disadvantages. We then briefly summarize the main achievements of omics studies, including epigenome, transcriptome, proteome, and metabolome analyses, as well as the main findings of functional cellular assays, the results of which imply that alterations in neurotransmission, metabolism, the cell cycle, and the immune system may be partially responsible for the pathophysiology of major psychiatric disorders such as schizophrenia. Finally, we discuss the future utility of peripheral samples for the development of biomarkers and tailor-made therapies, such as multimodal assays that are used as a battery of disease and trait pathways and that might be potent and complimentary tools for use in psychiatric research. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

Impact of endocrine hyperfunction and phosphate wasting on bone in McCune-Albright syndrome.

PubMed

Lala, R; Matarazzo, P; Andreo, M; Defilippi, C; de Sanctis, C

2002-01-01

Skin dysplasia, as café-au-lait spots, bone fibrous dysplasia and peripheral endocrinopathies are the main clinical features of McCune-Albright syndrome (MAS). This illness is due to activating mutations of the Gsalpha protein and is spread with a mosaic pattern in affected tissues that consist of intermixed areas of normal and mutated cells. Peripheral endocrine secretion, free of hypothalamic pituitary control, is the hallmark of the endocrine syndromes: precocious puberty, Cushing's syndrome, hyperthyroidism and gigantism/acromegaly. In addition, phosphate wasting as hyperphosphaturia is often present. The impact of hormonal hypersecretion and phosphate loss on the bones of patients with MAS is poorly understood both in normal and fibrous bone tissue. As hypercortisolism and hyperthyroidism increase bone resorption, hyperestrogenism and growth hormone hypersecretion stimulate bone growth and mineralization, and phosphate wasting reduces bone mineral content. All these actions can be exerted at varying times and degrees in a single patient on lesional and non-lesional bones. Sonographic evidence of multiple diffused hyperechogenic spots in the testes of patients with MAS do not seem to be related to alterations in calcium-phosphate metabolism but rather to zonal dysplasia/hyperplasia of testicular tissue.

Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis

PubMed Central

Jenkins, Trisha A.; Nguyen, Jason C. D.; Polglaze, Kate E.; Bertrand, Paul P.

2016-01-01

The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. Manipulation of tryptophan levels, acutely or chronically, by depletion or supplementation, is an experimental procedure for modifying peripheral and central serotonin levels. These studies have allowed us to establish the role of serotonin in higher order brain function in both preclinical and clinical situations and have precipitated the finding that low brain serotonin levels are associated with poor memory and depressed mood. The gut-brain axis is a bi-directional system between the brain and gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. An influence of gut microbiota on behaviour is becoming increasingly evident, as is the extension to tryptophan and serotonin, producing a possibility that alterations in the gut may be important in the pathophysiology of human central nervous system disorders. In this review we will discuss the effect of manipulating tryptophan on mood and cognition, and discuss a possible influence of the gut-brain axis. PMID:26805875

(18)F-sodium fluoride PET/CT for the in vivo visualization of Mönckeberg's sclerosis in a diabetic patient.

PubMed

Quirce, R; Martínez-Rodríguez, I; Banzo, I; de Arcocha-Torres, M; Jiménez-Bonilla, J F; Martínez-Amador, N; Ibáñez-Bravo, S; Ramos, L; Amado, J A; Carril, J M

2015-01-01

Diabetes is a major frequent cause of atherosclerosis vascular disease. Arterial calcification in diabetic patients is responsible for peripheral vascular involvement. Molecular imaging using (18)F-sodium fluoride ((18)F-NaF) positron emission tomography (PET)/computed tomography (CT) has been recently proposed as a marker to study the in vivo mineralization process in the atheroma plaque. A 69-year-old man with a history of type 2 diabetes and no clinical evidence of peripheral arterial disease underwent an (18)F-NaF PET/CT scan. A linear, well-defined (18)F-NaF uptake was detected along the femoral arteries. In addition, the CT component of the PET/CT identified an unsuspected "tram-track" calcification in his femoral arteries, suggestive of medial calcification (Mönckeberg's sclerosis). In other vascular territories, focal (18)F-NaF uptake was also detected in carotid and aorta atheroma plaques. Molecular imaging with (18)F-NaF PET/CT might provide new functional information about the in vivo vascular calcification process in diabetic patients. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

The next 10 years in the management of peripheral artery disease: perspectives from the 'PAD 2009' Conference.

PubMed

Norgren, L; Hiatt, W R; Dormandy, J A; Hirsch, A T; Jaff, M R; Diehm, C; Baumgartner, I; Belch, J J F

2010-09-01

To briefly inform on the conclusions from a conference on the next 10 years in the management of peripheral artery disease (PAD). International participation, invited presentations and open discussion were based on the following issues: Why is PAD under-recognised? Health economic impact of PAD; funding of PAD research; changes of treatment options? Aspects on clinical trials and regulatory views; and the role of guidelines. A relative lack of knowledge about cardiovascular risk and optimal management of PAD patients exists not only among the public, but also in parts of the health-care system. Specialists are required to act for improved information. More specific PAD research is needed for risk management and to apply the best possible evaluation of evidence for treatment strategies. Better strategies for funding are required based on, for example, public/private initiatives. The proportion of endovascular treatments is steadily increasing, more frequently based on observational studies than on randomised controlled trials. The role of guidelines is therefore important to guide the profession in the assessment of most relevant treatment. Copyright 2010 European Society for Vascular Surgery. All rights reserved.

Methodology and technology for peripheral and central blood pressure and blood pressure variability measurement: current status and future directions - Position statement of the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability.

PubMed

Stergiou, George S; Parati, Gianfranco; Vlachopoulos, Charalambos; Achimastos, Apostolos; Andreadis, Emanouel; Asmar, Roland; Avolio, Alberto; Benetos, Athanase; Bilo, Grzegorz; Boubouchairopoulou, Nadia; Boutouyrie, Pierre; Castiglioni, Paolo; de la Sierra, Alejandro; Dolan, Eamon; Head, Geoffrey; Imai, Yutaka; Kario, Kazuomi; Kollias, Anastasios; Kotsis, Vasilis; Manios, Efstathios; McManus, Richard; Mengden, Thomas; Mihailidou, Anastasia; Myers, Martin; Niiranen, Teemu; Ochoa, Juan Eugenio; Ohkubo, Takayoshi; Omboni, Stefano; Padfield, Paul; Palatini, Paolo; Papaioannou, Theodore; Protogerou, Athanasios; Redon, Josep; Verdecchia, Paolo; Wang, Jiguang; Zanchetti, Alberto; Mancia, Giuseppe; O'Brien, Eoin

2016-09-01

Office blood pressure measurement has been the basis for hypertension evaluation for almost a century. However, the evaluation of blood pressure out of the office using ambulatory or self-home monitoring is now strongly recommended for the accurate diagnosis in many, if not all, cases with suspected hypertension. Moreover, there is evidence that the variability of blood pressure might offer prognostic information that is independent of the average blood pressure level. Recently, advancement in technology has provided noninvasive evaluation of central (aortic) blood pressure, which might have attributes that are additive to the conventional brachial blood pressure measurement. This position statement, developed by international experts, deals with key research and practical issues in regard to peripheral blood pressure measurement (office, home, and ambulatory), blood pressure variability, and central blood pressure measurement. The objective is to present current achievements, identify gaps in knowledge and issues concerning clinical application, and present relevant research questions and directions to investigators and manufacturers for future research and development (primary goal).

Cannabinoids and Pain: Sites and Mechanisms of Action.

PubMed

Starowicz, Katarzyna; Finn, David P

2017-01-01

The endocannabinoid system, consisting of the cannabinoid 1 receptor (CB 1 R) and cannabinoid 2 receptor (CB 2 R), endogenous cannabinoid ligands (endocannabinoids), and metabolizing enzymes, is present throughout the pain pathways. Endocannabinoids, phytocannabinoids, and synthetic cannabinoid receptor agonists have antinociceptive effects in animal models of acute, inflammatory, and neuropathic pain. CB 1 R and CB 2 R located at peripheral, spinal, or supraspinal sites are important targets mediating these antinociceptive effects. The mechanisms underlying the analgesic effects of cannabinoids likely include inhibition of presynaptic neurotransmitter and neuropeptide release, modulation of postsynaptic neuronal excitability, activation of the descending inhibitory pain pathway, and reductions in neuroinflammatory signaling. Strategies to dissociate the psychoactive effects of cannabinoids from their analgesic effects have focused on peripherally restricted CB 1 R agonists, CB 2 R agonists, inhibitors of endocannabinoid catabolism or uptake, and modulation of other non-CB 1 R/non-CB 2 R targets of cannabinoids including TRPV1, GPR55, and PPARs. The large body of preclinical evidence in support of cannabinoids as potential analgesic agents is supported by clinical studies demonstrating their efficacy across a variety of pain disorders. © 2017 Elsevier Inc. All rights reserved.

Immune and Neuroendocrine Mechanisms of Stress Vulnerability and Resilience

PubMed Central

Ménard, Caroline; Pfau, Madeline L; Hodes, Georgia E; Russo, Scott J

2017-01-01

Diagnostic criteria for mood disorders including major depressive disorder (MDD) largely ignore biological factors in favor of behavioral symptoms. Compounding this paucity of psychiatric biomarkers is a need for therapeutics to adequately treat the 30–50% of MDD patients who are unresponsive to traditional antidepressant medications. Interestingly, MDD is highly prevalent in patients suffering from chronic inflammatory conditions, and MDD patients exhibit higher levels of circulating pro-inflammatory cytokines. Together, these clinical findings suggest a role for the immune system in vulnerability to stress-related psychiatric illness. A growing body of literature also implicates the immune system in stress resilience and coping. In this review, we discuss the mechanisms by which peripheral and central immune cells act on the brain to affect stress-related neurobiological and neuroendocrine responses. We specifically focus on the roles of pro-inflammatory cytokine signaling, peripheral monocyte infiltration, microglial activation, and hypothalamic-pituitary-adrenal axis hyperactivity in stress vulnerability. We also highlight recent evidence suggesting that adaptive immune responses and treatment with immune modulators (exogenous glucocorticoids, humanized antibodies against cytokines) may decrease depressive symptoms and thus represent an attractive alternative to the current antidepressant treatments. PMID:27291462

Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission

PubMed Central

Du, Xiaona; Hao, Han; Gigout, Sylvain; Huang, Dongyang; Yang, Yuehui; Li, Li; Wang, Caixue; Sundt, Danielle; Jaffe, David B.; Zhang, Hailin; Gamper, Nikita

2014-01-01

Peripheral sensory ganglia contain somata of afferent fibres conveying somatosensory inputs to the central nervous system. Growing evidence suggests that the somatic/perisomatic region of sensory neurons can influence peripheral sensory transmission. Control of resting membrane potential (Erest) is an important mechanism regulating excitability, but surprisingly little is known about how Erest is regulated in sensory neuron somata or how changes in somatic/perisomatic Erest affect peripheral sensory transmission. We first evaluated the influence of several major ion channels on Erest in cultured small-diameter, mostly capsaicin-sensitive (presumed nociceptive) dorsal root ganglion (DRG) neurons. The strongest and most prevalent effect on Erest was achieved by modulating M channels, K2P and 4-aminopiridine-sensitive KV channels, while hyperpolarization-activated cyclic nucleotide-gated, voltage-gated Na+, and T-type Ca2+ channels to a lesser extent also contributed to Erest. Second, we investigated how varying somatic/perisomatic membrane potential, by manipulating ion channels of sensory neurons within the DRG, affected peripheral nociceptive transmission in vivo. Acute focal application of M or KATP channel enhancers or a hyperpolarization-activated cyclic nucleotide-gated channel blocker to L5 DRG in vivo significantly alleviated pain induced by hind paw injection of bradykinin. Finally, we show with computational modelling how somatic/perisomatic hyperpolarization, in concert with the low-pass filtering properties of the t-junction within the DRG, can interfere with action potential propagation. Our study deciphers a complement of ion channels that sets the somatic Erest of nociceptive neurons and provides strong evidence for a robust filtering role of the somatic and perisomatic compartments of peripheral nociceptive neuron. PMID:25168672

Peripheral nerve block in patients with Ehlers-Danlos syndrome, hypermobility type: a case series.

PubMed

Neice, Andrew E; Stubblefield, Eryn E; Woodworth, Glenn E; Aziz, Michael F

2016-09-01

Ehlers-Danlos syndrome (EDS) is an inherited disease characterized by defects in various collagens or their post translational modification, with an incidence estimated at 1 in 5000. Performance of peripheral nerve block in patients with EDS is controversial, due to easy bruising and hematoma formation after injections as well as reports of reduced block efficacy. The objective of this study was to review the charts of EDS patients who had received peripheral nerve block for any evidence of complications or reduced efficacy. Case series, chart review. Academic medical center. Patients with a confirmed or probable diagnosis of EDS who had received a peripheral nerve block in the last 3 years were identified by searching our institutions electronic medical record system. The patients were classified by their subtype of EDS. Patients with no diagnosed subtype were given a probable subtype based on a chart review of the patient's symptoms. Patient charts were reviewed for any evidence of complications or reduced block efficacy. A total of 21 regional anesthetics, on 16 unique patients were identified, 10 of which had a EDS subtype diagnosis. The majority of these patients had a diagnosis of hypermobility-type EDS. No block complications were noted in any patients. Two block failures requiring repeat block were noted, and four patients reported uncontrolled pain on postoperative day one despite successful placement of a peripheral nerve catheter. Additionally, blocks were performed without incident in patients with classical-type and vascular-type EDS although the number was so small that no conclusions can be drawn about relative safety of regional anesthesia in these groups. This series fails to show an increased risk of complications of peripheral nerve blockade in patients with hypermobility-type EDS. Copyright © 2016 Elsevier Inc. All rights reserved.

VIBROTACTILE THRESHOLD AND PIN-PRICK SENSITIVITY AS INDICATORS OF SUBCLINICAL CHANGES IN SOMATOSENSORY FUNCTION: EFFECTS OF ENVIRONMENTAL EXPOSURE TO ARSENIC IN DRINKING WATER.

EPA Science Inventory

Peripheral neuropathy is a classical symptom of arsenic poisoning. Nerve conduction velocity (NCV) is the preferred measure for clinical assessment of peripheral neuropathy, but this method is not practical for field studies. Alternative methods available for assessing functi...

[Vasculitic Peripheral Neuropathies: Clinical Features and Diagnostic Laboratory Tests].

PubMed

Ogata, Katsuhisa

2016-03-01

Vasculitic peripheral neuropathy (VPN) occurs due to ischemic changes of peripheral nerves, resulting from a deficit of vascular blood supply due to damaged vasa nervorum leading to vasculitis. VPN usually manifests as sensorimotor or sensory disturbances accompanied by pain, presenting as a type of multiple mononeuropathy, with a scattered distribution in distal limbs. VPN may also present as a mononeuropathy, distal symmetric polyneuropathy, plexopathy, or radiculopathy. The rapidity of VPN is variable, ranging from days to months, with symptoms occasionally changing with the appearance of new lesions. Careful history taking and neurological examination provides an exact diagnosis. The most common cause of VPN is primary vasculitis predominantly affecting small vessels, including vasa nervorum, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and polyarteritis nodosa. Similar vasculitic processes can also result from a systemic collagen disorder or secondary vasculitis. Electrophysiological studies and pathological investigation of biopsied peripheral nerves and muscles are important for diagnosis of vasculitis. Serological tests, including ANCA, are useful for diagnosis of vasculitis. Accurate neurological examinations are essential for diagnosis and evaluation of clinical course.

Phenytoin: neuroprotection or neurotoxicity?

PubMed

Keppel Hesselink, Jan M; Kopsky, David J

2017-06-01

Phenytoin is an 80-year young molecule and new indications are still emerging. The neuroprotective potential of phenytoin has been evaluated for decades. Recently, a positive phase II trial supported its further development in the treatment of optic neuritis in multiple sclerosis. In 1942, however, peripheral neuritis was first reported to be an adverse event of phenytoin, and since then a small but steady stream of publications discussed peripheral polyneuropathy as being a possible adverse event of phenytoin. We have reviewed the literature and concluded there is some supportive evidence for a reversible polyneuropathy after the oral use of phenytoin, though with no evidence for clear neurotoxicity on the level of peripheral nerves. This is probably due to the fact that the pharmacological effects of phenytoin, based on the stabilizing effect of the voltage-gated sodium channels, make impairment of nerve conduction in asymptomatic and symptomatic reversible polyneuropathies plausible. Clear toxically-induced phenytoin-related polyneuropathies, however, are extremely rare and are always related to high dose or high plasma levels of phenytoin, mostly developing during many years of therapy. We could only find one case of a probable reversible chronic phenytoin intoxication resulting in a biopsy proven axonal atrophy with secondary demyelination and signs of remyelination. All case series and case reports published are insufficient in detail to prove a clear causal relation between phenytoin intake and the induction of a peripheral polyneuropathy. Phenytoin does not lead to irreversible toxicity of the peripheral nerves and might, on the other hand, have neuroprotective properties.

Hypothyroidism: Can It Cause Peripheral Neuropathy?

MedlinePlus

... of Privacy Practices Notice of Nondiscrimination Manage Cookies Advertising Mayo Clinic is a not-for-profit organization and proceeds from Web advertising help support our mission. Mayo Clinic does not ...

Peripheral Avascular Retina in a Term Male Neonate With Microvillus Inclusion Disease and Pancreatic Insufficiency.

PubMed

Paulus, Yannis M; Alcorn, Deborah M; Gaynon, Michael; Moshfeghi, Darius M

2015-05-01

The authors present the first case of peripheral avascular retina in a term male neonate with pancreatic exocrine insufficiency, atypical microvillus inclusion disease, flat tympanograms, and recurrent urinary tract infections. Clinical examination showed avascular peripheral retina to posterior zone II temporally, with a flat stage 1-like demarcation line, and no plus disease. Genetic testing results were normal. The patient developed peripheral neovascularization and underwent panretinal photocoagulation. This case likely represents mild Norrie disease, familial exudative vitreoretinopathy, or incontinentia pigmenti due to a Wnt signaling abnormality. While these conditions are usually more severe, a variable spectrum of Wnt abnormalities exists throughout the body. Copyright 2015, SLACK Incorporated.

Florid cemento-osseous dysplasia and peripheral giant cell granuloma in a patient with neurofibromatosis 1.

PubMed

Sarmento, Dmitry José de Santana; Carvalho, Sérgio Henrique Gonçalves de; Araújo, José Cadmo Wanderley Peregrino de; Carvalho, Marianne de Vasconcelos; Silveira, Éricka Janine Dantas da

2017-01-01

We report a 35-year-old mulatto female patient with neurofibromatosis Type 1 who presented with facial asymmetry. The patient had two lesions: florid cemento-osseous dysplasia associated with peripheral giant cell granuloma. She was referred for surgical treatment of the peripheral giant cell granuloma and the florid cemento-osseous dysplasia was treated conservatively by a multidisciplinary team. So far, no changes have been observed in the patient's clinical status. We observed no recurrence of peripheral giant cell granuloma. To the best of our knowledge, the present case is the first report of a patient with neurofibromatosis Type 1 associated with a giant cell lesion and florid cemento-osseous dysplasia.

Florid cemento-osseous dysplasia and peripheral giant cell granuloma in a patient with neurofibromatosis 1*

PubMed Central

Sarmento, Dmitry José de Santana; de Carvalho, Sérgio Henrique Gonçalves; de Araújo Filho, José Cadmo Wanderley Peregrino; Carvalho, Marianne de Vasconcelos; da Silveira, Éricka Janine Dantas

2017-01-01

We report a 35-year-old mulatto female patient with neurofibromatosis Type 1 who presented with facial asymmetry. The patient had two lesions: florid cemento-osseous dysplasia associated with peripheral giant cell granuloma. She was referred for surgical treatment of the peripheral giant cell granuloma and the florid cemento-osseous dysplasia was treated conservatively by a multidisciplinary team. So far, no changes have been observed in the patient's clinical status. We observed no recurrence of peripheral giant cell granuloma. To the best of our knowledge, the present case is the first report of a patient with neurofibromatosis Type 1 associated with a giant cell lesion and florid cemento-osseous dysplasia. PMID:28538890

Iron Homeostasis in Peripheral Nervous System, Still a Black Box?

PubMed Central

Taveggia, Carla

2014-01-01

Abstract Significance: Iron is the most abundant transition metal in biology and an essential cofactor for many cellular enzymes. Iron homeostasis impairment is also a component of peripheral neuropathies. Recent Advances: During the past years, much effort has been paid to understand the molecular mechanism involved in maintaining systemic iron homeostasis in mammals. This has been stimulated by the evidence that iron dyshomeostasis is an initial cause of several disorders, including genetic and sporadic neurodegenerative disorders. Critical Issues: However, very little has been done to investigate the physiological role of iron in peripheral nervous system (PNS), despite the development of suitable cellular and animal models. Future Directions: To stimulate research on iron metabolism and peripheral neuropathy, we provide a summary of the knowledge on iron homeostasis in the PNS, on its transport across the blood–nerve barrier, its involvement in myelination, and we identify unresolved questions. Furthermore, we comment on the role of iron in iron-related disorder with peripheral component, in demyelinating and metabolic peripheral neuropathies. Antioxid. Redox Signal. 21, 634–648. PMID:24409826

Ultrasound-Guided Regional Anesthesia and Patient Safety: Update of an Evidence-Based Analysis.

PubMed

Neal, Joseph M

2016-01-01

In 2010, the American Society of Regional Anesthesia and Pain Medicine's evidence-based medicine assessment of ultrasound (US)-guided regional anesthesia (UGRA) analyzed the effect of this nerve localization technology on patient safety. That analysis focused on 4 important regional anesthesia complications: peripheral nerve injury, local anesthetic systemic toxicity (LAST), hemidiaphragmatic paresis (HDP), and pneumothorax. In the intervening 5 years, further research has allowed us to refine our original conclusions. This update reviews previous findings and critically evaluates new literature published since late 2009 that compares the patient safety attributes of UGRA with those of traditional nerve localization methods. As with the previous version of this exercise, analysis focused on randomized controlled trials that compared UGRA with an alternative neural localization method and case series of more than 500 patients. The Jadad score was used to grade individual study quality, and conclusions were graded as to strength of evidence. Of those randomized controlled trials identified by our search techniques, 28 compared the incidence of postoperative nerve symptoms, 27 assessed LAST parameters, 7 studied HDP, and 9 reported the incidence of pneumothorax. The current analysis strengthens our original conclusions that US guidance has no significant effect on the incidence of postoperative neurologic symptoms and that UGRA reduces the incidence and intensity of HDP but does so in an unpredictable manner. Conversely, emerging evidence supports the effectiveness of US guidance for reducing LAST across its clinical presentation continuum. The predicted frequency of pneumothorax has grown smaller in tandem with increased experience with US-guided supraclavicular block. This evidence-based review summarizes both the power and the limitations of UGRA as a tool for improving patient safety. Since the original 2010 publication of this analysis, evidence has continued to support the concept that ultrasound (US) guidance does not meaningfully affect the incidence of peripheral nerve injury (PNI) associated with regional anesthesia. Similar confirmatory evidence attests to US guidance reducing the incidence and intensity of hemidiaphragmatic paresis (HDP) but not eliminating it. Literature published since late 2009 reports the effective role of US guidance in reducing the incidence of local anesthetic systemic toxicity and allows calculation of a lower predicted frequency of pneumothorax associated with US-guided supraclavicular blocks.

[The Efficacy of Near-Infrared Devices in Facilitating Peripheral Intravenous Access in Children: A Systematic Review and Subgroup Meta-Analysis].

PubMed

Kuo, Chia-Chi; Feng, I-Jung; Lee, Wei-Jing

2017-10-01

Peripheral intravenous access is a common and invasive procedure that is performed in pediatric clinical settings. Children often have difficult intravenous-access problems that may not only increase staff stress but also affect the timeliness of immediate treatments. To determine the efficacy of near-infrared devices in facilitating peripheral intravenous access in children, using a systematic review and meta-analysis. Six databases, namely the Index to Taiwan Periodical Literature System, Airiti Library, CINAHL, Cochrane Library, PubMed/MEDLINE, and ProQuest were searched for related articles that were published between the earliest year available and February 2017. The search was limited to studies on populations of children that used either a randomized controlled trial or controlled clinical trial approach and used the key words "near-infrared devices" AND "peripheral intravenous access." The 12 articles that met these criteria were included in the analysis. The Cochrane Collaboration bias assessment tool was used to assess the methodological quality. In addition, RevMan 5.3.5 software was used to conduct the meta-analysis. The near-infrared devices did not significantly improve the first-attempt success rate, number of attempts, or the procedural time of peripheral intravenous access in children. However, the subgroup analysis of difficult intravenous-access factors revealed a significant improvement in the first-attempt success rate of children with difficult intravenous access scores (OR = 1.83, p = .03). Near-infrared devices may improve the first-attempt success rate in children with difficult intravenous access by allowing healthcare professionals to visualize the peripheral veins. Therefore, we suggest that the difficult intravenous-access score be used as a screening tool to suggest when to apply near-infrared devices to children with difficult peripheral intravenous access in order to maximize efficacy of treatment.

Correlation of total serum immunoglobulin E level, sputum, and peripheral eosinophil count in assessing the clinical severity in bronchial asthma.

PubMed

Kumar, Roshan M; Pajanivel, R; Koteeswaran, G; Menon, Surendra K; Charles, Pravin Mv

2017-01-01

Asthma is a chronic inflammatory disorder of the airway with involvement of various cellular populations and release of many inflammatory mediators. Eosinophils and serum immunoglobulin E (IgE) are considered a good marker of airway inflammation in asthma. The correlation of clinical assessment with various markers of airway inflammation in asthma is not well established in the Indian population. This study aims to study the correlation of serum IgE, sputum eosinophil count, and peripheral eosinophil count with clinical severity of Asthma. This is a cross-sectional study involving 76 stable asthmatic patients of 18-60 years of age attending the pulmonary medicine OPD. Spirometry measured at baseline. Participants were categorized according to the GINA criteria based on clinical symptoms and pulmonary function test. Blood samples were collected for peripheral eosinophil count, serum IgE levels, and sputum samples for eosinophil count. All three parameters were compared with severity of asthma. The correlation of sputum eosinophil count, peripheral eosinophil count, and serum IgE with severity of asthma was analyzed by Pearson's Chi-square test, Fisher's exact test, and the correlation coefficient was reported together with standard error of the estimate. The mean age of patients in our study was 37.42 years and 56.6% were male. There was a significant inverse correlation between serum IgE levels and predicted forced expiratory volume 1 s (FEV1). Sputum eosinophilia was significantly seen in severe persistent asthma patients (19.7%). There was a significant inverse correlation between sputum eosinophil count and predicted FEV1and forced vital capacity. We also found there was a significant association between peripheral eosinophil count, sputum eosinophil count, and elevated serum IgE (g100 IU/mL) with severe persistent asthma. The assessment of sputum eosinophil count is simple, inexpensive, noninvasive, and direct measurement of airway inflammation. It could be the preferred method in monitoring airway inflammation and guided management in day-to-day practice.

Trial Watch: Adoptive cell transfer for oncological indications

PubMed Central

Aranda, Fernando; Buqué, Aitziber; Bloy, Norma; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Fridman, Wolf Hervé; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2015-01-01

One particular paradigm of anticancer immunotherapy relies on the administration of (potentially) tumor-reactive immune effector cells. Generally, these cells are obtained from autologous peripheral blood lymphocytes (PBLs) ex vivo (in the context of appropriate expansion, activation and targeting protocols), and re-infused into lymphodepleted patients along with immunostimulatory agents. In spite of the consistent progress achieved throughout the past two decades in this field, no adoptive cell transfer (ACT)-based immunotherapeutic regimen is currently approved by regulatory agencies for use in cancer patients. Nonetheless, the interest of oncologists in ACT-based immunotherapy continues to increase. Accumulating clinical evidence indicates indeed that specific paradigms of ACT, such as the infusion of chimeric antigen receptor (CAR)-expressing autologous T cells, are associated with elevated rates of durable responses in patients affected by various neoplasms. In line with this notion, clinical trials investigating the safety and therapeutic activity of ACT in cancer patients are being initiated at an ever increasing pace. Here, we review recent preclinical and clinical advances in the development of ACT-based immunotherapy for oncological indications. PMID:26451319

Unilateral pigmentary degeneration of the retina associated with heterochromia iridis.

PubMed

Grisanti, S; Diestelhorst, M; Lebek, J; Walter, P; Heimann, K

1998-12-01

For the past 5 years, a 56-year-old patient has been displaying monocular progressive pigmentary changes in the left eye. Heterochromy of the left eye has been known since childhood. The other eye is clinically and functionally normal. The patient was adopted and he has no children. Therefore, we have no family history. The patient was examined clinically and by means of electroretinography, electrooculography, perimetry, computer tomography, pulsatile ocular blood flow (POBF) measurement, serology and Doppler sonography. Electrophysiology displayed a considerable reduction of scotopic and photopic ERGs, a reduced dark-through, and a reduced light-rise in the left eye, whereas the fellow eye was normal. The visual field was limited to 5 deg around the fixation point, and a peripheral crescent-shaped arch encircled the temporal-inferior quadrant concomitant to the pigmentary changes. By computer tomography and Doppler sonography a vascular affection was excluded. The left eye displayed lower POBF values. All serological tests were found negative. The clinical picture and negative exclusion criteria indicate a unilateral retinitis pigmentosa. However, with regard to the literature an unequivocal diagnosis can only be made upon hereditary evidence.

Trial Watch: Adoptive cell transfer for oncological indications.

PubMed

Aranda, Fernando; Buqué, Aitziber; Bloy, Norma; Castoldi, Francesca; Eggermont, Alexander; Cremer, Isabelle; Fridman, Wolf Hervé; Fucikova, Jitka; Galon, Jérôme; Spisek, Radek; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2015-11-01

One particular paradigm of anticancer immunotherapy relies on the administration of (potentially) tumor-reactive immune effector cells. Generally, these cells are obtained from autologous peripheral blood lymphocytes (PBLs) ex vivo (in the context of appropriate expansion, activation and targeting protocols), and re-infused into lymphodepleted patients along with immunostimulatory agents. In spite of the consistent progress achieved throughout the past two decades in this field, no adoptive cell transfer (ACT)-based immunotherapeutic regimen is currently approved by regulatory agencies for use in cancer patients. Nonetheless, the interest of oncologists in ACT-based immunotherapy continues to increase. Accumulating clinical evidence indicates indeed that specific paradigms of ACT, such as the infusion of chimeric antigen receptor (CAR)-expressing autologous T cells, are associated with elevated rates of durable responses in patients affected by various neoplasms. In line with this notion, clinical trials investigating the safety and therapeutic activity of ACT in cancer patients are being initiated at an ever increasing pace. Here, we review recent preclinical and clinical advances in the development of ACT-based immunotherapy for oncological indications.

Laquinimod dampens hyperactive cytokine production in Huntington's disease patient myeloid cells.

PubMed

Dobson, Lucianne; Träger, Ulrike; Farmer, Ruth; Hayardeny, Liat; Loupe, Pippa; Hayden, Michael R; Tabrizi, Sarah J

2016-06-01

Huntington's disease (HD) is a neurodegenerative condition characterized by pathology in the brain and peripheral tissues. Hyperactivity of the innate immune system, due in part to NFκB pathway dysregulation, is an early and active component of HD. Evidence suggests targeting immune disruption may slow disease progression. Laquinimod is an orally active immunomodulator that down-regulates proinflammatory cytokine production in peripheral blood mononuclear cells, and in the brain down-regulates astrocytic and microglial activation by modulating NFκB signalling. Laquinimod had beneficial effects on inflammation, brain atrophy and disease progression in multiple sclerosis (MS) in two phase III clinical trials. This study investigated the effects of laquinimod on hyperactive proinflammatory cytokine release and NFκB signalling in HD patient myeloid cell cultures. Monocytes from manifest (manHD) and pre-manifest (preHD) HD gene carriers and healthy volunteers (HV) were treated with laquinimod and stimulated with lipopolysaccharide. After 24 h pre-treatment with 5 μM laquinimod, manHD monocytes released lower levels of IL-1β, IL-5, IL-8, IL-10, IL-13 and TNFα in response to stimulation. PreHD monocytes released lower levels of IL-8, IL-10 and IL-13, with no reduction observed in HV monocytes. The effects of laquinimod on dysfunctional NFκB signalling in HD was assessed by inhibitor of kappa B (IκB) degradation kinetics, nuclear translocation of NFκB and interactions between IκB kinase (IKK) and HTT, in HD myeloid cells. No differences were observed between laquinimod-treated and untreated conditions. These results provide evidence that laquinimod dampens hyper-reactive cytokine release from manHD and preHD monocytes, with a much reduced effect on HV monocytes. Evidence suggests targeting CNS and peripheral immune disruption may slow Huntington's disease (HD) neurodegenerative processes. The effects of laquinimod, an orally active immunomodulator, on hyperactive cytokine release and dysfunctional NFκB signalling in stimulated myeloid cell cultures from pre-manifest and manifest HD gene carriers and healthy volunteers were investigated. Laquinimod dampened cytokine release but did not impact NFκB signalling. Read the Editorial Highlight for this article on page 670. © 2016 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota

PubMed Central

van den Hoogen, Ward J.; Laman, Jon D.; ’t Hart, Bert A.

2017-01-01

Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination, axonal damage, and symptoms such as fatigue and disability. Although the cause of MS is not known, the infiltration of peripherally activated immune cells into the CNS has a key pathogenic role. Accumulating evidence supports an important role of diet and gut microbiota in immune-mediated diseases. Preclinical as well as clinical studies suggest a role for gut microbiota and dietary components in MS. Here, we review these recent studies on gut microbiota and dietary interventions in MS and its animal model experimental autoimmune encephalomyelitis. We also propose directions for future research. PMID:28928747

Circadian Rhythm Disturbances in Mood Disorders: Insights into the Role of the Suprachiasmatic Nucleus

PubMed Central

2017-01-01

Circadian rhythm disturbances are a common symptom among individuals with mood disorders. The suprachiasmatic nucleus (SCN), in the ventral part of the anterior hypothalamus, orchestrates physiological and behavioral circadian rhythms. The SCN consists of self-sustaining oscillators and receives photic and nonphotic cues, which entrain the SCN to the external environment. In turn, through synaptic and hormonal mechanisms, the SCN can drive and synchronize circadian rhythms in extra-SCN brain regions and peripheral tissues. Thus, genetic or environmental perturbations of SCN rhythms could disrupt brain regions more closely related to mood regulation and cause mood disturbances. Here, we review clinical and preclinical studies that provide evidence both for and against a causal role for the SCN in mood disorders. PMID:29230328

Sexually transmitted pathogens in pregnant women in a rural South African community.

PubMed Central

O'Farrell, N; Hoosen, A A; Kharsany, A B; van den Ende, J

1989-01-01

One hundred and ninety three consecutive pregnant women attending peripheral antenatal clinics attached to Ngwelezana Hospital, Empangeni, Kwa-Zulu, were examined for evidence of sexually transmitted pathogens. The following incidences were found: Trichomonas vaginalis 49.2% (95), Candida spp 38.3% (74), Chlamydia trachomatis 11.4% (22), Gardnerella vaginalis 6.2% (12), Neisseria gonorrhoeae 5.7% (11), positive syphilis serology results 11.9% (23), hepatitis B surface antigen 4.1% (eight). No woman had antibody to human immunodeficiency virus (HIV). Dyskaryotic smears were found in 20 (10.4%). Human papillomavirus (HPV) was detected cytologically in 11 (5.7%). The range of sexually transmitted pathogens found in this rural community was similar to that found in urban groups studied in South Africa. PMID:2807289

CHD risk equivalents and the metabolic syndrome. Trial evidence supports aggressive management.

PubMed

Thompson, Paul D

2003-08-01

Updated guidelines issued by the National Cholesterol Education Program's 2001 Adult Treatment Panel III (ATP III) reaffirm the importance of intensive management of low density lipoprotein cholesterol (LDL-C) in patients with established coronary heart disease (CHD). Clinical studies also show that diabetes, peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease are CHD risk equivalents that require intensive therapeutic lifestyle changes and drug therapy to prevent associated morbidity and mortality. Likewise, the metabolic syndrome is a secondary target of treatment. Drug therapy usually starts with an LDL-C-lowering agent, such as a statin. If LDL-C and non-high-density lipoprotein cholesterol goals are not achieved, statin therapy should be intensified or a fibrate or niacin should be added.

Peripheral calcifying cystic odontogenic tumour of the maxillary gingiva.

PubMed

de Lima, Ana Paula; Kitakawa, Dárcio; Almeida, Janete Dias; Brandão, Adriana Aigotti Haberbeck; Anbinder, Ana Lia

2012-08-23

Odontogenic tumors are lesions that are derived from remnants of the components of the developing tooth germ. The calcifying cystic odontogenic tumor or calcifying odontogenic cyst is a benign cystic neoplasm of odontogenic origin that is characterized by an ameloblastoma-like epithelium and ghost cells. Calcifying cystic odontogenic tumor may be centrally or peripherally located, and its ghost cells may exhibit calcification, as first described by Gorlin in 1962. Most peripheral calcifying cystic odontogenic tumors are located in the anterior gingiva of the mandible or maxilla. Authors report a rare case of a peripheral calcifying cystic odontogenic tumor of the maxillary gingiva. A 39-year-old male patient presented with a fibrous mass on the attached buccal gingiva of the upper left cuspid teeth. It was 0.7-cm-diameter, painless and it was clinically diagnosed as a peripheral ossifying fibroma. After an excisional biopsy, the diagnosis was peripheric calcifying cystic odontogenic tumor. The patient was monitored for five years following the excision, and no recurrence was detected. All biopsy material must be sent for histological examination. If the histological examination of gingival lesions with innocuous appearance is not performed, the frequency of peripheral calcifying cystic odontogenic tumor and other peripheral odontogenic tumors may be underestimated.

Reclaiming the Periphery: Automated Kinetic Perimetry for Measuring Peripheral Visual Fields in Patients With Glaucoma.

PubMed

Mönter, Vera M; Crabb, David P; Artes, Paul H

2017-02-01

Peripheral vision is important for mobility, balance, and guidance of attention, but standard perimetry examines only <20% of the entire visual field. We report on the relation between central and peripheral visual field damage, and on retest variability, with a simple approach for automated kinetic perimetry (AKP) of the peripheral field. Thirty patients with glaucoma (median age 68, range 59-83 years; median Mean Deviation -8.0, range -16.3-0.1 dB) performed AKP and static automated perimetry (SAP) (German Adaptive Threshold Estimation strategy, 24-2 test). Automated kinetic perimetry consisted of a fully automated measurement of a single isopter (III.1.e). Central and peripheral visual fields were measured twice on the same day. Peripheral and central visual fields were only moderately related (Spearman's ρ, 0.51). Approximately 90% of test-retest differences in mean isopter radius were < ±4 deg. Relative to the range of measurements in this sample, the retest variability of AKP was similar to that of SAP. Patients with similar central visual field loss can have strikingly different peripheral visual fields, and therefore measuring the peripheral visual field may add clinically valuable information.

Electroacupuncture for chemotherapy-induced peripheral neuropathy: study protocol for a pilot multicentre randomized, patient-assessor-blinded, controlled trial

PubMed Central

2013-01-01

Background Chemotherapy-induced peripheral neuropathy (CIPN) is the main dose-limiting side effect of neurotoxic chemotherapeutic agents. CIPN can lead not only to loss of physical function, difficulties in activities of daily living (ADLs), and decreased quality of life, but also to dose reduction, delay or even cessation of treatment. Currently, there are few proven effective treatments for CIPN. This randomized controlled clinical trial is designed to evaluate the effects and safety of electroacupuncture (EA) for patients with CIPN. Methods/design This is a multicenter, two-armed, parallel-design, patient-assessor-blinded, randomized, sham-controlled clinical trial. Forty eligible patients with CIPN will be randomized in a ratio of 1:1 to the EA or sham EA arms. During the treatment phase, patients will undergo eight sessions of verum EA or sham EA twice weekly for four weeks, and then will be followed-up for eight weeks. Electrical stimulation in the EA group will consist of a mixed frequency of 2/120 Hz and 80% of bearable intensity. Sham EA will be applied to non-acupoints, with shallow needle insertion and no current. All outcomes and analyses of results will be assessed by researchers blinded to treatment allocation. The effects of EA on CIPN will be evaluated according to both subjective and objective outcome measures. The primary outcome measure will be the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire to assess CIPN (QLQ-CIPN20). The secondary outcome measures will be the results on the numerical rating scale, the Semmes-Weinstein monofilament test, the nerve conduction study, and the EORTC QLQ-C30, as well as the patient’s global impression of change and adverse events. Safety will be assessed at each visit. Discussion The results of this on-going study will provide clinical evidence for the effects and safety of EA for CIPN compared with sham EA. Trial registration Clinical Research Information Service: KCT0000506 PMID:23945074

Neuropeptides, neurogenic inflammation and complex regional pain syndrome (CRPS).

PubMed

Birklein, Frank; Schmelz, Martin

2008-06-06

This review explains symptoms and nature of neuropeptide signaling and its importance for clinical symptoms of CRPS. Neurogenic inflammation regularly accompanies excitation of primary afferent nociceptors. It has two major components-plasma extravasation and vasodilatation. The most important mediators are the calcitonin gene-related peptide (CGRP) and substance P (SP). After peripheral trauma immune reaction (e.g. cytokines) and the attempts of the tissue to regenerate (e.g. growth factors) sensitize nociceptors and amplify neurogenic inflammation. This cascade of events has been demonstrated in rat models of CRPS. Clinical findings in these animals strongly resemble clinical findings in CRPS, and can be prevented by anti-cytokine and anti-neuropeptide treatment. In CRPS patients, there is meanwhile also plenty of evidence that neurogenic inflammation contributes to clinical presentation. Increased cytokine production was demonstrated, as well as facilitated neurogenic inflammation. Very recently even "non-inflammatory" signs of CRPS (hyperhidrosis, cold skin) have been linked to neuropeptide signaling. Surprisingly, there was even moderately increased neurogenic inflammation in unaffected body regions. This favors the possibility that CRPS patients share genetic similarities. The future search for genetic commonalities will help us to further unravel the "mystery" CRPS.

Evidence of immunosuppression by Demodex canis.

PubMed

Barriga, O O; al-Khalidi, N W; Martin, S; Wyman, M

1992-04-01

Three clinically normal beagles, 3 beagles with localized demodectic mange (LDM), and 3 beagles with generalized demodectic mange (GDM) were investigated simultaneously 1-3 and 4-6 weeks from the appearance of the clinical signs. Blood clinical examination and reactivity of peripheral lymphocytes to Con A and PHA were investigated in the first instance, and reactivity to Con A, PHA, and LPS in the second. Eight aliquots were used in each blastogenesis assay for each dog. All dogs were negative for rheumatoid factor. The results of blastogenesis showed that many observations were distributed non-normally, and that not all dogs in each group responded homogeneously. Comparison of blastogenesis results between dogs demands careful statistical analysis. Responses to mitogens were normal in all dogs at 1-3 weeks except for the LDM dogs that showed an increased response to PHA. Only the response to Con A was moderately inhibited in the LDM dogs at 4-6 weeks. All responses were severely depressed in the GDM dogs at 4-6 weeks. This means that immunosuppression follows rather than precedes the clinical manifestations of GDM, and implies that the phenomenon is induced by the parasite or the host's reaction to it.

Non-conventional features of peripheral serotonin signalling - the gut and beyond.

PubMed

Spohn, Stephanie N; Mawe, Gary M

2017-07-01

Serotonin was first discovered in the gut, and its conventional actions as an intercellular signalling molecule in the intrinsic and extrinsic enteric reflexes are well recognized, as are a number of serotonin signalling pharmacotherapeutic targets for treatment of nausea, diarrhoea or constipation. The latest discoveries have greatly broadened our understanding of non-conventional actions of peripheral serotonin within the gastrointestinal tract and in a number of other tissues. For example, it is now clear that bacteria within the lumen of the bowel influence serotonin synthesis and release by enterochromaffin cells. Also, serotonin can act both as a pro-inflammatory and anti-inflammatory signalling molecule in the intestinal mucosa via activation of serotonin receptors (5-HT 7 or 5-HT 4 receptors, respectively). For decades, serotonin receptors have been known to exist in a variety of tissues other than the gut, but studies have now provided strong evidence for physiological roles of serotonin in several important processes, including haematopoiesis, metabolic homeostasis and bone metabolism. Furthermore, evidence for serotonin synthesis in peripheral tissues outside of the gut is emerging. In this Review, we expand the discussion beyond gastrointestinal functions to highlight the roles of peripheral serotonin in colitis, haematopoiesis, energy and bone metabolism, and how serotonin is influenced by the gut microbiota.

Unseen but present danger: improving the safe prescribing of anti-embolism stockings (AES).

PubMed

Bradley, Alison

2014-01-01

A strong evidence base exists supporting thromboprophylaxis for venous thromboembolism (VTE) in surgical patients. Given the ageing population, obesity epidemic, and rise in type 2 diabetes, VTE and peripheral vascular disease (PAD) are likely to become an escalating problem. PAD is a contraindication to the use of anti-embolism stockings (AES). Half of those patients diagnosed with PAD report no symptoms, potentially underestimating its prevalence. Implementation of guidelines for thromboprophylaxis, including the safe prescribing of AES, is therefore imperative. The aims of this project were to establish whether thromboprophylaxis was being prescribed correctly, and appropriately, to all surgical inpatients. This included documented evidence that peripheral pulses had been examined - and, in the case of diabetic patients, that there was documentation of full peripheral neurovascular examination - before AES were prescribed. Data were collected from case notes of all surgical inpatients. Foundation year 1 doctors (FY1s) completed a questionnaire assessing their knowledge of local guidelines. Teaching sessions and posters summarising local guidelines were delivered to FY1s. Appropriate pharmacological prescribing improved from 57.69% to 100%. AES were appropriately prescribed for 65.38% of patients. Post intervention this increased to 79.17%. 0% had documented peripheral neurovascular examination. This increased to 50% post intervention.

Electrically stimulated signals from a long-term Regenerative Peripheral Nerve Interface.

PubMed

Langhals, Nicholas B; Woo, Shoshana L; Moon, Jana D; Larson, John V; Leach, Michelle K; Cederna, Paul S; Urbanchek, Melanie G

2014-01-01

Despite modern technological advances, the most widely available prostheses provide little functional recovery beyond basic grasping. Although sophisticated upper extremity prostheses are available, optimal prosthetic interfaces which give patients high-fidelity control of these artificial limbs are limited. We have developed a novel Regenerative Peripheral Nerve Interface (RPNI), which consists of a unit of free muscle that has been neurotized by a transected peripheral nerve. In conjunction with a biocompatible electrode on the muscle surface, the RPNI facilitates signal transduction from a residual peripheral nerve to a neuroprosthetic limb. The purpose of this study was to explore signal quality and reliability in an RPNI following an extended period of implantation. Following a 14-month maturation period, electromyographic signal generation was evaluated via electrical stimulation of the innervating nerve. The long-term RPNI was viable and healthy, as demonstrated by evoked compound muscle action potentials as well as histological tissue analysis. Signals exceeding 4 mV were successfully acquired and amplitudes were consistent across multiple repetitions of applied stimuli. There were no evident signs of muscle denervation, significant scar tissue, or muscle necrosis. This study provides further evidence that after a maturation period exceeding 1 year, reliable and consistent signals can still be acquired from an RPNI.

Anatomic evidence for peripheral neural processing in mammalian graviceptors

NASA Technical Reports Server (NTRS)

Ross, M. D.

1985-01-01

Ultrastructural study of utricular and saccular maculas demonstrates that their innervation patterns are complex. There is a clustering of type I and type II hair cells based upon a sharing of afferents, a system of efferent-type beaded fibers that is of intramacular (mostly calyceal) origin, and a plexus-like arrangement of afferents and efferents at many sites in the neuroepithelium. Results suggest that information concerning linear acceleration is processed peripherally, beginning at the hair cell level, before being sent to the central nervous system. The findings may supply a structural basis for peripheral adaptation to a constant stimulus, and for lateral inhibition to improve signal relative to noise.

Carpal tunnel syndrome: just a peripheral neuropathy?

PubMed

Fernández-de-Las-Peñas, César; Plaza-Manzano, Gustavo

2018-06-05

Carpal tunnel syndrome (CTS) is considered just a peripheral neuropathy of the upper extremity associated to the compression of the median nerve. There is evidence suggesting the presence of complex sensitization mechanisms in CTS. These processes are manifested by symptoms in extra-median regions and the presence of bilateral sensory and motor impairments. These sensory and motor changes are not associated to electrodiagnostic findings. The presence of sensitization mechanisms suggests that CTS should not be considered just as a peripheral neuropathy. The presence of altered nociceptive gain processing should be considered for therapeutic management of CTS by considering the application of therapeutic interventions that modulate nociceptive barrage into the CNS.

Common questions about the diagnosis and management of fibromyalgia.

PubMed

Kodner, Charles

2015-04-01

Fibromyalgia has a distinct pathophysiology involving central amplification of peripheral sensory signals. Core symptoms are chronic widespread pain, fatigue, and sleep disturbance. Most patients with fibromyalgia have muscle pain and tenderness, forgetfulness or problems concentrating, and significant functional limitations. Fibromyalgia is diagnosed using an updated set of clinical criteria that no longer depend on tender point examination; laboratory testing may rule out other disorders that commonly present with fatigue, such as anemia and thyroid disease. Patients with fibromyalgia should be evaluated for comorbid functional pain syndromes and mood disorders. Management of fibromyalgia should include patient education, symptom relief, and regular aerobic physical activity. Serotoninnorepinephrine reuptake inhibitors, tricyclic antidepressants, antiepileptics, and muscle relaxants have the strongest evidence of benefit for improving pain, fatigue, sleep symptoms, and quality of life. Multiple complementary and alternative medicine therapies have been used but have limited evidence of effectiveness. Opioids should be used to relieve pain in carefully selected patients only if alternative therapies are ineffective.

A focused exercise regimen improves clinical measures of balance in patients with peripheral neuropathy.

PubMed

Richardson, J K; Sandman, D; Vela, S

2001-02-01

To determine the effect of a specific exercise regimen on clinical measures of postural stability and confidence in a population with peripheral neuropathy (PN). Prospective, controlled, single blind study. Outpatient clinic of a university hospital. Twenty subjects with diabetes mellitus and electrodiagnostically confirmed PN. Ten subjects underwent a 3-week intervention exercise regimen designed to increase rapidly available distal strength and balance. The other 10 subjects performed a control exercise regimen. Unipedal stance time, functional reach, tandem stance time, and score on the activities-specific balance and confidence (ABC) scale. The intervention subjects, but not the control subjects, showed significant improvement in all 3 clinical measures of balance and nonsignificant improvement on the ABC scale. A brief, specific exercise regimen improved clinical measures of balance in patients with diabetic PN. Further studies are needed to determine if this result translates into a lower fall frequency in this high-risk population.

Foot Kinetics and Kinematics Profile in Type 2 Diabetes Mellitus with Peripheral Neuropathy: A Hospital Based Study from South India.

PubMed

Hazari, Animesh; Maiya, Arun G; N, Shivashankara K

2018-02-01

A kinetic change in thefoot like altered plantar pressure is the most common etiological risk factor for causing foot ulcers among people with diabetes mellitus. Kinematic alterations in joint angle and spatiotemporal parameters of the gait have also been frequently observed in participants with diabetes peripheral neuropathy. Diabetes peripheral neuropathy is the most common long-term standing complication of type 2 diabetes mellitus. It leads to various micro and macrovascular related complication of the foot. There is a gap in theliteraturefor biomechanical evaluation and assessment in type 2 diabetes mellitus with peripheral neuropathy in Indian population. The aim of the study was to assess and determine the biomechanical changes including kinetics and kinematics of foot among diabetic peripheral neuropathy. The cross-sectional study was conducted at Diabetic Foot Clinic, Kasturba Hospital, Manipal University, Manipal, Karnataka, India. A total of 120 participants with type 2 diabetes mellitus and peripheral neuropathywere recruited under the purposive sampling method. Participants with any active ulceration or amputation were excluded from the study. The mean age, height, weight, body mass index, duration of diabetes was 57±14 year, 164±11cm, 61±18kg, 24± 3, 12±7 year respectively. There were significant changes in overall biomechanical profile along with clinical manifestations of diabetes peripheral neuropathy.The regression analysis showed statistical significance for dynamic maximum plantar pressure at forefoot with age, weight, height, duration of diabetes, body mass index, knee & ankle joint angle at toe-off phase of gait cycle,pinprick sensation and ankle reflex (R=.71,R =.55, F (12, 108)=521.9 kPa, p=.002) Conclusions: From the present study, we conclude that people with type 2 diabetes mellitus and peripheral neuropathy have significant changes in their foot kinetics and kinematicsparameters. Therefore, they could be at higher risk of foot ulceration with underlying neuropathy and biomechanically associated problems.

Peripheral Sensory Neuropathy and associated factors among adult diabetes mellitus patients in Bahr Dar, Ethiopia.

PubMed

Jember, Gashaw; Melsew, Yayehirad Alemu; Fisseha, Berihu; Sany, Kedir; Gelaw, Asmare Yitayeh; Janakiraman, Balamurugan

2017-01-01

Diabetic sensory neuropathy is a common form of microvascular complication among diabetic patients. The swiftly growing population of people living with diabetes in Ethiopia and lack of elaborated scientific data on peripheral sensory neuropathy among diabetic population in Ethiopia prompted this work. This study was set out to assess the enormity and associated factors of peripheral sensory neuropathy among diabetes patients attending chronic illness clinic of Felege Hiwot Regional Referral Hospital, Bahr Dar, Northwest Ethiopia. An institution based cross-sectional study was conducted at Felege Hiwot Referral Hospital chronic illness clinic using Michigan neuropathy screening instrument tool for diabetic peripheral sensory neuropathy on 408 diabetic patients during 2016. Data were collected using interview, patient record review, anthropometric measurements and physical examination. Both bivariate and multivariate binary logistic regression was employed to identify factors associated with peripheral sensory neuropathy. Odds ratios with their 95% CI and P value less than 0.05 used to determine statistically significant associations. A total of 368 patients were included with the mean age of 49 ± 14.3 years. The overall prevalence of Peripheral Sensory Neuropathy was found to be 52.2%. The major associated factors identified by multivariate analysis were age >50 years: AOR: 3.0 CI [1.11, 7.89]; overweight and obese: AOR: 7.3 CI [3.57, 14.99]; duration of DM: AOR: 3.4 CI [1.75, 6.60]; not involved in physical exercise: AOR: 4.8 CI [1.90, 7.89]; male gender: AOR: 2.4 CI [1.18, 5.05]. Almost half of the diabetic patients who attended Felege Hiwot regional referral hospital during study period were found to present with peripheral sensory neuropathy. Socio-demographic and bio characteristics like patients age, Body Mass Index, level of physical activity and marital status were significantly associated with diabetic peripheral sensory neuropathy.

Somatosensory evoked potentials in the assessment of peripheral neuropathies: Commented results of a survey among French-speaking practitioners and recommendations for practice.

PubMed

Morizot-Koutlidis, R; André-Obadia, N; Antoine, J-C; Attarian, S; Ayache, S S; Azabou, E; Benaderette, S; Camdessanché, J-P; Cassereau, J; Convers, P; d'Anglejean, J; Delval, A; Durand, M-C; Etard, O; Fayet, G; Fournier, E; Franques, J; Gavaret, M; Guehl, D; Guerit, J-M; Krim, E; Kubis, N; Lacour, A; Lozeron, P; Mauguière, F; Merle, P-E; Mesrati, F; Mutschler, V; Nicolas, G; Nordine, T; Pautot, V; Péréon, Y; Petiot, P; Pouget, J; Praline, J; Salhi, H; Trébuchon, A; Tyvaert, L; Vial, C; Zola, J-M; Zyss, J; Lefaucheur, J-P

2015-05-01

Somatosensory evoked potentials (SSEPs) are increasingly performed for the assessment of peripheral neuropathies, but no practical guidelines have yet been established in this specific application. To determine the relevant indication criteria and optimal technical parameters for SSEP recording in peripheral neuropathy investigation. A survey was conducted among the French-speaking practitioners with experience of SSEP recording in the context of peripheral neuropathies. The results of the survey were analyzed and discussed to provide recommendations for practice. SSEPs appear to be a second-line test when electroneuromyographic investigation is not sufficiently conclusive, providing complementary and valuable information on central and proximal peripheral conduction in the somatosensory pathways. Guidelines for a standardized recording protocol, including the various parameters to be measured, are proposed. We hope that these proposals will help to recognize the value of this technique in peripheral neuropathy assessment in clinical practice. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Topical amitriptyline and ketamine for the treatment of neuropathic pain.

PubMed

Mercadante, Sebastiano

2015-01-01

A neuropathy is a disturbance of function or pathological change in nerves. In some cases, peripheral neuropathic pain may occur due to a lesion or disease of the peripheral somatosensory nervous system. Efficacy of different agents for peripheral neuropathic pain conditions is less than optimal. The administration of topical analgesics might be an option, due to the potential of reduced adverse effects and increased patient compliance. There is major interest in compounding topical analgesics for peripheral neuropathic pain, but several challenges remain for this approach. Topical analgesics have the potential to be a valuable additional approach for the management of peripheral neuropathic pain. Topical amitriptyline-ketamine combination (AK) is a promising agent for peripheral neuropathic pain conditions. Some studies have shown its efficacy in neuropathic pain conditions. However, this data was not uniformely obtained and its role remains still controversial. Efficacy may depend on many factors, including the choice of the vehicle, the concentration, the pain site, and specific diseases. More studies are necessary to support the use of AK in clinical practice.

Imaging Stem Cell Therapy for the Treatment of Peripheral Arterial Disease

PubMed Central

Ransohoff, Julia D.; Wu, Joseph C.

2013-01-01

Arteriosclerotic cardiovascular diseases are among the leading causes of morbidity and mortality worldwide. Therapeutic angiogenesis aims to treat ischemic myocardial and peripheral tissues by delivery of recombinant proteins, genes, or cells to promote neoangiogenesis. Concerns regarding the safety, side effects, and efficacy of protein and gene transfer studies have led to the development of cell-based therapies as alternative approaches to induce vascular regeneration and to improve function of damaged tissue. Cell-based therapies may be improved by the application of imaging technologies that allow investigators to track the location, engraftment, and survival of the administered cell population. The past decade of investigations has produced promising clinical data regarding cell therapy, but design of trials and evaluation of treatments stand to be improved by emerging insight from imaging studies. Here, we provide an overview of pre-clinical and clinical experience using cell-based therapies to promote vascular regeneration in the treatment of peripheral arterial disease. We also review four major imaging modalities and underscore the importance of in vivo analysis of cell fate for a full understanding of functional outcomes. PMID:22239638

Splenic marginal zone lymphoma.

PubMed

Piris, Miguel A; Onaindía, Arantza; Mollejo, Manuela

Splenic marginal zone lymphoma (SMZL) is an indolent small B-cell lymphoma involving the spleen and bone marrow characterized by a micronodular tumoral infiltration that replaces the preexisting lymphoid follicles and shows marginal zone differentiation as a distinctive finding. SMZL cases are characterized by prominent splenomegaly and bone marrow and peripheral blood infiltration. Cells in peripheral blood show a villous cytology. Bone marrow and peripheral blood characteristic features usually allow a diagnosis of SMZL to be performed. Mutational spectrum of SMZL identifies specific findings, such as 7q loss and NOTCH2 and KLF2 mutations, both genes related with marginal zone differentiation. There is a striking clinical variability in SMZL cases, dependent of the tumoral load and performance status. Specific molecular markers such as 7q loss, p53 loss/mutation, NOTCH2 and KLF2 mutations have been found to be associated with the clinical variability. Distinction from Monoclonal B-cell lymphocytosis with marginal zone phenotype is still an open issue that requires identification of precise and specific thresholds with clinical meaning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evidence that shock-induced immune suppression is mediated by adrenal hormones and peripheral beta-adrenergic receptors.

PubMed

Cunnick, J E; Lysle, D T; Kucinski, B J; Rabin, B S

1990-07-01

Our previous work has demonstrated that presentations of mild foot-shock to Lewis rats induces a suppression of splenic and peripheral blood lymphocyte responses to nonspecific T-cell mitogens. The present study demonstrated that adrenalectomy prevented the shock-induced suppression of the mitogenic response of peripheral blood T-cells but did not attenuate the suppression of splenic T-cells. Conversely, the beta-adrenergic receptor antagonists, propranolol and nadolol, attenuated the shock-induced suppression of splenic T-cells in a dose-dependent manner but did not attenuate suppression of the blood mitogen response. These data indicate that distinct mechanisms mediate the shock-induced suppression of T-cell responsiveness to mitogens in the spleen and the peripheral blood. The results indicate that the peripheral release of catecholamines is responsible for splenic immune suppression and that adrenal hormones, which do not interact with beta-adrenergic receptors, are responsible for shock-induced suppression of blood mitogenic responses.

Analysis of the peripheral immune response in patients with neurocysticercosis: evidence for T cell reactivity to parasite glycoprotein and vesicular fluid antigens.

PubMed

Restrepo, B I; Aguilar, M I; Melby, P C; Teale, J M

2001-10-01

In neurocysticercosis (NCC), it is thought that the long-term survival of the parasite within the human brain is due in part to the ability of the cestode to suppress the local immune response. When the parasite dies, the immunosuppression is apparently lost and a strong local inflammatory response then develops. In contrast, little is known about the immunologic response that may occur in the peripheral immune system of these patients. In this study, the status of the peripheral (extracerebral) cellular and humoral response was evaluated in patients with a history of NCC. The in vitro proliferation of peripheral blood mononuclear cells to mitogens and foreign antigens was similar in patients and controls. Importantly, a substantive response was elicited by two Taenia solium metacestode antigens. In addition, 8 of 10 patients had a detectable humoral response to the antigenic glycoproteins of the cestode. Considering both the cellular and humoral response, all of the patients with NCC presented an active peripheral immunity.

Peripheral formalin injection induces unique spinal cord microglial phenotypic changes

PubMed Central

Fu, Kai-Yuan; Tan, Yong-Hui; Sung, Backil; Mao, Jianren

2014-01-01

Microglia are resident immune cells of brain and activated by peripheral tissue injury. In the present study, we investigated the possible induction of several microglial surface immunomolecules in the spinal cord, including leukocyte common antigen (LCA/CD45), MHC class I antigen, MHC class II antigen, Fc receptor, and CD11c following formalin injection into the rat’s hind paw. CD45 and MHC class I were upregulated in the activated microglia, which was evident on day 3 with the peak expression on day 7 following peripheral formalin injection. There was a very low basal expression of MHC class II, CD11c, and the Fc receptor, which did not change after the formalin injection. These results, for the first time, indicate that peripheral formalin injection can induce phenotypic changes of microglia with distinct upregulation of CD45 and MHC class I antigen. The data suggest that phenotypic changes of the activated microglia may be a unique pattern of central changes following peripheral tissue injury. PMID:19015000

The Diabetes Telephone Study: Design and challenges of a pragmatic cluster randomized trial to improve diabetic peripheral neuropathy treatment.

PubMed

Adams, Alyce S; Bayliss, Elizabeth A; Schmittdiel, Julie A; Altschuler, Andrea; Dyer, Wendy; Neugebauer, Romain; Jaffe, Marc; Young, Joseph D; Kim, Eileen; Grant, Richard W

2016-06-01

Challenges to effective pharmacologic management of symptomatic diabetic peripheral neuropathy include the limited effectiveness of available medicines, frequent side effects, and the need for ongoing symptom assessment and treatment titration for maximal effectiveness. We present here the rationale and implementation challenges of the Diabetes Telephone Study, a randomized trial designed to improve medication treatment, titration, and quality of life among patients with symptomatic diabetic peripheral neuropathy. We implemented a pragmatic cluster randomized controlled trial to test the effectiveness of an automated interactive voice response tool designed to provide physicians with real-time patient-reported data about responses to newly prescribed diabetic peripheral neuropathy medicines. A total of 1834 primary care physicians treating patients in the diabetes registry at Kaiser Permanente Northern California were randomized into the intervention or control arm. In September 2014, we began identification and recruitment of patients assigned to physicians in the intervention group who receive three brief interactive calls every 2 months after a medication is prescribed to alleviate diabetic peripheral neuropathy symptoms. These calls provide patients with the opportunity to report on symptoms, side effects, self-titration of medication dose and overall satisfaction with treatment. We plan to compare changes in self-reported quality of life between the intervention group and patients in the control group who receive three non-interactive automated educational phone calls. Successful implementation of this clinical trial required robust stakeholder engagement to help tailor the intervention and to address pragmatic concerns such as provider time constraints. As of 27 October 2015, we had screened 2078 patients, 1447 of whom were eligible for participation. We consented and enrolled 1206 or 83% of those eligible. Among those enrolled, 53% are women and the mean age is 67 (standard deviation = 12) years. The racial ethnic make-up is 56% White, 8% Asian, 13% Black or African American, and 19% Hispanic or Latino. Innovative strategies are needed to guide improvements in healthcare delivery for patients with symptomatic diabetic peripheral neuropathy. This trial aims to assess whether real-time collection and clinical feedback of patient treatment experiences can reduce patient symptom burden. Implementation of a clinical trial closely involving clinical care required researchers to partner with clinicians. If successful, this intervention provides a critical information feedback loop that would optimize diabetic peripheral neuropathy medication titration through widely available interactive voice response technology. © The Author(s) 2016.

Clinical Forms of Canine Visceral Leishmaniasis in Naturally Leishmania infantum–Infected Dogs and Related Myelogram and Hemogram Changes

PubMed Central

Roatt, Bruno Mendes; Aguiar-Soares, Rodrigo Dian de Oliveira; Reis, Levi Eduardo Soares; Carvalho, Maria das Graças; Carneiro, Cláudia Martins; Giunchetti, Rodolfo Cordeiro; Bouillet, Leoneide Erica Maduro; Lemos, Denise Silveira; Coura-Vital, Wendel; Reis, Alexandre Barbosa

2013-01-01

Hematological analysis has limited applications for disease diagnosis in Leishmania infantum–infected dogs, but it can be very important in evaluating the clinical forms of the disease and in understanding the evolution of canine visceral leishmaniasis (CVL) pathogenesis. Recently, we demonstrated that alterations in leucopoiesis and erythropoiesis are related to clinical status and bone marrow parasite density in dogs naturally infected by L. infantum. To further characterize these alterations, we evaluated the association between the hematological parameters in bone marrow and peripheral blood alterations in groups of L. infantum–infected dogs: asymptomatic I (AD-I: serum negative/PCR+), asymptomatic II (AD-II: serum positive), oligosymptomatic (OD), and symptomatic (SD). Results were compared with those from noninfected dogs (NID). The SD group was found to present a decrease in erythropoietic lineage with concomitant reductions in erythrocytes, hemoglobin, and hematocrit parameters, resulting in anemia. The SD group also had increased neutrophils and precursors and decreased band eosinophils and eosinophils, leading to peripheral blood leucopenia. In the AD-II group, lymphocytosis occurred in both the peripheral blood and the bone marrow compartments. The SD group exhibited lymphocytosis in the bone marrow, with lymphopenia in the peripheral blood. In contrast, the AD-I group, showed no significant changes suggestive of CVL, presenting normal counts in bone marrow and peripheral blood. Our results showed for the first time that important changes in hematopoiesis and hematological parameters occur during ongoing CVL in naturally infected dogs, mainly in symptomatic disease. Taken together, our results based on myelogram and hemogram parameters enable better understanding of the pathogenesis of the anemia, lymphocytosis, and lymphopenia, as well as the leucopenia (eosinopenia and monocytopenia), that contribute to CVL prognosis. PMID:24376612

Six cases of sporadic schwannomatosis: Topographic distribution and outcomes of peripheral nerve tumors.

PubMed

Chick, G; Victor, J; Hollevoet, N

2017-10-01

The diagnosis of schwannomatosis is often overestimated and is based on the existence of multiple peripheral nerve tumors composed exclusively of schwannomas, in the absence of clinical signs of neurofibromatosis type 2 (NF2). Sporadic forms are much more frequent than familial forms. The objective of this study was to describe the distribution of peripheral nerve tumors and investigate the outcomes of schwannomas in the context of sporadic schwannomatosis. We conducted a retrospective study of patients who fulfilled clinical diagnostic criteria for sporadic schwannomatosis. Six patients were reviewed with a mean follow-up of 38.5months (27-60months). Patients' demographic, clinical, radiographic, and pathologic data were extracted. All patients underwent slit-lamp examination, enhanced brain magnetic resonance imaging (MRI) and a spinal MRI. Enucleation that preserved nerve continuity was performed in symptomatic patients. On average, patients were 36years of age at the time of diagnosis with no sex predominance. The topographic distribution of the peripheral nerve tumors was always unilateral and most frequently targeted the upper limb. In four cases, the tumors involved the same peripheral nerve exclusively. The average number of nerve tumors observed per patient was 4.7 (2-8). The outcome after enucleation was marked by the systematic appearance of new tumors. After enucleation, no recurrence or malignant transformation was observed at the final follow-up. There was no transition to a NF2 configuration. The absence of neurofibroma and NF2 criteria makes schwannomatosis a diagnosis of exclusion. While a good prognosis can be expected following enucleation, two risks related to neurofibromatosis type 3 (NF3) are worth monitoring: the transition to NF2, particularly in young patients, and the appearance of new tumors. Copyright © 2017 SFCM. Published by Elsevier Masson SAS. All rights reserved.

[Protocol for peripheral parenteral nutrition management ready to use in surgical patients].

PubMed

Pinzón Espitia, Olga Lucia; Varón Vega, Martha Liliana

2014-10-03

Patients undergoing elective surgery, require a comprehensive clinical treatment that tends to maintain or prevent deterioration of nutritional status and promote clinical outcomes, and in turn improve the safety of parenteral nutrition therapy through optimization of technology, as a option aimed at minimizing risk and lower operating costs in institutions providing health services. To review the literature in order to study the requirements and recommendations of peripheral parenteral nutritional support and / or complementary ready to use in people undergoing surgery. Data synthesis after reviewing the relevant literature, to allow the protocol design. The search was conducted in the following databases: PubMed, Medline, Embase and ScienceDirect. Peripheral parenteral nutrition is a ready to use alternative nutritional support that improves the contribution Protein-Energy and demonstrate improvements in patient safety, decrease costs and increase patient satisfaction. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Use of Silver Diamine Fluoride for Dental Caries Management in Children and Adolescents, Including Those with Special Health Care Needs.

PubMed

Crystal, Yasmi O; Marghalani, Abdullah A; Ureles, Steven D; Wright, John Timothy; Sulyanto, Rosalyn; Divaris, Kimon; Fontana, Margherita; Graham, Laurel

2017-09-15

This manuscript presents evidence-based guidance on the use of 38 percent silver diamine fluoride (SDF) for dental caries management in children and adolescents, including those with special health care needs. A guideline workgroup formed by the American Academy of Pediatric Dentistry developed guidance and an evidence-based recommendation regarding the application of 38 percent SDF to arrest cavitated caries lesions in primary teeth. The basis of the guideline's recommendation is evidence from an existing systematic review "Clinical trials of silver diamine fluoride in arresting caries among children: A systematic review." (JDR Clin Transl Res 2016;1[3]:201-10). A systematic search was conducted in PubMed®/MEDLINE, Embase®, Cochrane Central Register of Controlled Trials, and gray literature databases to identify randomized controlled trials and systematic reviews reporting on the effect of silver diamine fluoride and address peripheral issues such as adverse effects and cost. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of the evidence and the evidence-to-decision framework was employed to formulate a recommendation. The panel made a conditional recommendation regarding the use of 38 percent SDF for the arrest of cavitated caries lesions in primary teeth as part of a comprehensive caries management program. After taking into consideration the low cost of the treatment and the disease burden of caries, panel members were confident that the benefits of SDF application in the target populations outweigh its possible undesirable effects. Per GRADE, this is a conditional recommendation based on low-quality evidence. Conclusions and practical implications: The guideline intends to inform the clinical practices involving the application of 38 percent SDF to enhance dental caries management outcomes in children and adolescents, including those with special health care needs. These recommended practices are based upon the best available evidence to-date. A 38 percent SDF protocol is included in Appendix II.

Identification of e6a2 BCR-ABL fusion in a Philadelphia-positive CML with marked basophilia: implications for treatment strategy.

PubMed

Rohon, Peter; Divoka, Martina; Calabkova, Lenka; Mojzikova, Renata; Katrincsakova, Beata; Rusinakova, Zuzana; Lapcikova, Anna; Raida, Ludek; Faber, Edgar; Jarosova, Marie; Divoky, Vladimir; Indrak, Karel

2011-06-01

This is a case report of a 51 year old male with marked splenomegaly, basophilia, severe thrombocytopenia, anemia and high SFKL phosphorylation downstream of Bcr-Abl, investigated for association of the e6a2 BCR-ABL fusion gene and marked basophilia. The treatment strategy implications in patients with Philadelphia positive CML are described. RT-PCR and sequencing were carried out on the peripheral blood leukocytes to detect the type of BCR-ABL transcript. The BCR-ABL mutational status was assessed using sequencing of the RT-PCR products. The in vitro test of sensitivity to TKIs was based on detecting inhibited phosphorylation of the Crkl and Phospho-Src family kinases (SFK, Tyr416) using immunodetection. The cytogenetics revealed 90% of Ph+ (Philadelphia) cells in the bone marrow aspirate with no additional clonal chromosomal abnormalities at diagnosis. This correlated with an accelerated phase of the CML. Sequencing analysis of reverse transcribed and PCR amplified BCR-ABL transcript revealed a rare e6a2 fusion, with no evidence for Bcr-Abl kinase domain mutation. Western blot analysis showed high phosphorylation (activation) of Crkl and the Src family of kinases (P-SFK). In vitro test of sensitivity of the patients' leukemic cells to imatinib demonstrated sensitivity of Bcr-Abl tyrosine kinase to imatinib, as assessed by a decrease in phosphorylated Crkl and the disappearance of P-SFK, suggesting that P-Src reflects only the Bcr-Abl-dependent Src activity. The initial treatment strategy was reduced imatinib and search for an unrelated hematopoietic stem cell donor (according to the ELN recommendations). The patient was allografted with peripheral stem cells from an HLA- identical male donor but on day +70 graft failure occurred. He was allografted again with the peripheral stem cells from an HLA-identical female donor, engrafted on day +15 and showed 100% donor chimerism with no evidence of the e6a2 BCR-ABL fusion transcript on day +30. The clinical disease course in patients with the rare e6a2 BCR-ABL transcript variant is aggressive. This may be the result of increased kinase activity due to partial loss of the guanine exchange factor/dbl-like domain which mediates the interaction with several Ras-like G-proteins involved in cell proliferation, signal transduction, and cytoskeletal organization. For the above reasons, these patients should receive stem cell transplant immediately after a short course of treatment with imatinib/ dual Src/Abl kinase inhibitor or they should be registered in clinical trials with experimental agents.

Serum Uric Acid Levels and Diabetic Peripheral Neuropathy in Type 2 Diabetes: a Systematic Review and Meta-analysis.

PubMed

Yu, Shuai; Chen, Ying; Hou, Xu; Xu, Donghua; Che, Kui; Li, Changgui; Yan, Shengli; Wang, Yangang; Wang, Bin

2016-03-01

Previous studies suggested a possible association between serum uric acid levels and peripheral neuropathy in patients with type 2 diabetes, but no definite evidence was available. A systematic review and meta-analysis of relevant studies were performed to comprehensively estimate the association. Pubmed, Web of Science, Embase, and China Biology Medicine (CBM) databases were searched for eligible studies. Study-specific data were combined using random-effect or fixed-effect models of meta-analysis according to between-study heterogeneity. Twelve studies were finally included into the meta-analysis, which involved a total of 1388 type 2 diabetic patients with peripheral neuropathy and 4746 patients without peripheral neuropathy. Meta-analysis showed that there were obvious increased serum uric acid levels in diabetic patients with peripheral neuropathy (weighted mean difference [WMD] = 50.03 μmol/L, 95% confidence interval [95%CI] 22.14-77.93, P = 0.0004). Hyperuricemia was also significantly associated with increased risk of peripheral neuropathy in patients with type 2 diabetes (risk ratio [RR] = 2.83, 95%CI 2.13-3.76, P < 0.00001). Meta-analysis of two studies with adjusted risk estimates showed that hyperuricemia was independently associated with increased risk of peripheral neuropathy in type 2 diabetic patients (RR = 1.95, 95%CI 1.23-3.11, P = 0.005). Type 2 diabetic patients with peripheral neuropathy have obvious increased serum uric acid levels, and hyperuricemia is associated with increased risk of peripheral neuropathy. Further prospective cohort studies are needed to validate the impact of serum uric acid levels on peripheral neuropathy risk.

Neurotoxicity Associated with Platinum-Based Anti-Cancer Agents: What are the Implications of Copper Transporters?

PubMed

Stojanovska, Vanesa; McQuade, Rachel; Rybalka, Emma; Nurgali, Kulmira

2017-01-01

Platinum-based anti-cancer agents, which include cisplatin, carboplatin and oxaliplatin, are an important class of drugs used in clinical setting to treat a variety of cancers. The cytotoxic efficacy of these drugs is mediated by the formation of inter-strand and intrastrand crosslinks, or platinum adducts on nuclear DNA. There is also evidence demonstrating that mitochondrial DNA is susceptible to platinum-adduct damage in dorsal root ganglia neurons. Although all platinum-based agents form similar DNA adducts, they are quite different in terms of activation, systemic toxicity and tolerance. Platinum-based agents are well known for their neurotoxicity and gastrointestinal side-effects which are major causes for dose limitation and treatment discontinuation compromising the efficacy of anti-cancer treatment. Accumulating evidence in non-neuronal cells shows that the copper transport system is associated with platinum drug sensitivity and resistance. There is minimal research concerning the role of copper transporters within the central and peripheral nervous systems. It is unclear whether neurons are more sensitive to platinum-based drugs, are insufficient in drug clearance, or whether platinum accumulation affects intracellular copper status and coppermediated functions. Understanding these mechanisms is important as neurotoxicity is the predominant side-effect of platinum-based chemotherapy. This review highlights the role of copper transpor ters in drug influx, differences in drug activation and side-effects caused by platinum-based agents, as well as their association with central and peripheral neuropathies and gastrointestinal toxicities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Adoptive transfer of MART-1 T cell receptor transgenic lymphocytes and dendritic cell vaccination in patients with metastatic melanoma

PubMed Central

Chodon, Thinle; Comin-Anduix, Begonya; Chmielowski, Bartosz; Koya, Richard C; Wu, Zhongqi; Auerbach, Martin; Ng, Charles; Avramis, Earl; Seja, Elizabeth; Villanueva, Arturo; McCannel, Tara A.; Ishiyama, Akira; Czernin, Johannes; Radu, Caius G.; Wang, Xiaoyan; Gjertson, David W.; Cochran, Alistair J.; Cornetta, Kenneth; Wong, Deborah J.L.; Kaplan-lefko, Paula; Hamid, Omid; Samlowski, Wolfram; Cohen, Peter A.; Daniels, Gregory A.; Mukherji, Bijay; Yang, Lili; Zack, Jerome A.; Kohn, Donald B.; Heath, James R.; Glaspy, John A.; Witte, Owen N.; Baltimore, David; Economou, James S.; Ribas, Antoni

2014-01-01

Purpose It has been demonstrated that large numbers of tumor-specific T cells for adoptive cell transfer (ACT) can be manufactured by retroviral genetic engineering of autologous peripheral blood lymphocytes and expanding them over several weeks. In mouse models, this therapy is optimized when administered with dendritic cell (DC) vaccination. We developed a short one-week manufacture protocol to determine the feasibility, safety and antitumor efficacy of this double cell therapy. Experimnetal Design A clinical trial (NCT00910650) adoptively transferring MART-1 T cell receptor (TCR) transgenic lymphocytes together with MART-1 peptide pulsed DC vaccination in HLA-A2.1 patients with metastatic melanoma. Autologous TCR transgenic cells were manufactured in 6 to 7 days using retroviral vector gene transfer, and re-infused with (n = 10) or without (n = 3) prior cryopreservation. Results 14 patients with metastatic melanoma were enrolled and nine out of 13 treated patients (69%) showed evidence of tumor regression. Peripheral blood reconstitution with MART-1-specific T cells peaked within two weeks of ACT indicating rapid in vivo expansion. Administration of freshly manufactured TCR transgenic T cells resulted in a higher persistence of MART-1-specific T cells in the blood as compared to cryopreserved. Evidence that DC vaccination could cause further in vivo expansion was only observed with ACT using non-cryopreserved T cells. Conclusion Double cell therapy with ACT of TCR engineered T cells with a very short ex vivo manipulation and DC vaccines is feasible and results in antitumor activity, but improvements are needed to maintain tumor responses. PMID:24634374

Role of the vagus nerve in the development and treatment of diet‐induced obesity

PubMed Central

2016-01-01

Abstract This review highlights evidence for a role of the vagus nerve in the development of obesity and how targeting the vagus nerve with neuromodulation or pharmacology can be used as a therapeutic treatment of obesity. The vagus nerve innervating the gut plays an important role in controlling metabolism. It communicates peripheral information about the volume and type of nutrients between the gut and the brain. Depending on the nutritional status, vagal afferent neurons express two different neurochemical phenotypes that can inhibit or stimulate food intake. Chronic ingestion of calorie‐rich diets reduces sensitivity of vagal afferent neurons to peripheral signals and their constitutive expression of orexigenic receptors and neuropeptides. This disruption of vagal afferent signalling is sufficient to drive hyperphagia and obesity. Furthermore neuromodulation of the vagus nerve can be used in the treatment of obesity. Although the mechanisms are poorly understood, vagal nerve stimulation prevents weight gain in response to a high‐fat diet. In small clinical studies, in patients with depression or epilepsy, vagal nerve stimulation has been demonstrated to promote weight loss. Vagal blockade, which inhibits the vagus nerve, results in significant weight loss. Vagal blockade is proposed to inhibit aberrant orexigenic signals arising in obesity as a putative mechanism of vagal blockade‐induced weight loss. Approaches and molecular targets to develop future pharmacotherapy targeted to the vagus nerve for the treatment of obesity are proposed. In conclusion there is strong evidence that the vagus nerve is involved in the development of obesity and it is proving to be an attractive target for the treatment of obesity. PMID:26959077

The European Society of Regional Anaesthesia and Pain Therapy/American Society of Regional Anesthesia and Pain Medicine Recommendations on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia.

PubMed

Suresh, Santhanam; Ecoffey, Claude; Bosenberg, Adrian; Lonnqvist, Per-Anne; de Oliveira, Gildasio S; de Leon Casasola, Oscar; de Andrés, José; Ivani, Giorgio

2018-02-01

Dosage of local anesthetics (LAs) used for regional anesthesia in children is not well determined. In order to evaluate and come to a consensus regarding some of these controversial topics, The European Society of Regional Anaesthesia and Pain Therapy (ESRA) and the American Society of Regional Anesthesia and Pain Medicine (ASRA) developed a Joint Committee Practice Advisory on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia. Representatives from both ASRA and ESRA composed the joint committee practice advisory. Evidence-based recommendations were based on a systematic search of the literature. In cases where no literature was available, expert opinion was elicited. Spinal anesthesia with bupivacaine can be performed with a dose of 1 mg/kg for newborn and/or infant and a dose of 0.5 mg/kg in older children (>1 year of age). Tetracaine 0.5% is recommended for spinal anesthesia (dose, 0.07-0.13 mL/kg). Ultrasound-guided upper-extremity peripheral nerve blocks (eg, axillary, infraclavicular, interscalene, supraclavicular) in children can be performed successfully and safely using a recommended LA dose of bupivacaine or ropivacaine of 0.5 to 1.5 mg/kg. Dexmedetomidine can be used as an adjunct to prolong the duration of peripheral nerve blocks in children. High-level evidence is not yet available to guide dosage of LA used in regional blocks in children. The ASRA/ESRA recommendations intend to provide guidance in order to reduce the large variability of LA dosage currently observed in clinical practice.

Ultra-Widefield Steering-Based SD-OCT Imaging of the Retinal Periphery

PubMed Central

Choudhry, Netan; Golding, John; Manry, Matthew W.; Rao, Rajesh C.

2016-01-01

Objective To describe the spectral-domain optical coherence tomography (SD-OCT) features of peripheral retinal findings using an ultra-widefield (UWF) steering technique to image the retinal periphery. Design Observational study. Participants 68 patients (68 eyes) with 19 peripheral retinal features. Main Outcome Measures SD-OCT-based structural features. Methods Nineteen peripheral retinal features including: vortex vein, congenital hypertrophy of the retinal pigment epithelium (CHRPE), pars plana, ora serrata pearl, typical cystoid degeneration (TCD), cystic retinal tuft, meridional fold, lattice and cobblestone degeneration, retinal hole, retinal tear, rhegmatogenous retinal detachment (RRD), typical degenerative senile retinoschisis, peripheral laser coagulation scars, ora tooth, cryopexy scars (retinal tear and treated retinoblastoma scar), bone spicules, white without pressure, and peripheral drusen were identified by peripheral clinical examination. Near infrared (NIR) scanning laser ophthalmoscopy (SLO) images and SD-OCT of these entities were registered to UWF color photographs. Results SD-OCT resolved structural features of all peripheral findings. Dilated hyporeflective tubular structures within the choroid were observed in the vortex vein. Loss of retinal lamination, neural retinal attenuation, RPE loss or hypertrophy were seen in several entities including CHRPE, ora serrata pearl, TCD, cystic retinal tuft, meridional fold, lattice and cobblestone degenerations. Hyporeflective intraretinal spaces, indicating cystoid or schitic fluid, were seen in ora serrata pearl, ora tooth, TCD, cystic retinal tuft, meridional fold, retinal hole, and typical degenerative senile retinoschisis. The vitreoretinal interface, which often consisted of lamellae-like structures of the condensed cortical vitreous near or adherent to the neural retina, appeared clearly in most peripheral findings, confirming its association with many low-risk and vision-threatening pathologies such as lattice degeneration, meridional folds, retinal breaks, and RRDs. Conclusions UWF steering technique-based SD-OCT imaging of the retinal periphery is feasible with current commercially available devices, and provides detailed anatomical information of the peripheral retina, including benign and pathological entities, not previously imaged. This imaging technique may deepen our structural understanding of these entities, their potentially associated macular and systemic pathologies, and may influence decision-making in clinical practice, particularly in areas with teleretinal capabilities but poor access to retinal specialists. PMID:26992837

Diagnosis and therapeutic options for peripheral vasculitic neuropathy

PubMed Central

2015-01-01

Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen. Standard treatments include steroids, azathioprine, methotrexate and cyclophosphamide. More recently the B-cell antibody rituximab and intravenous immunoglobulins have shown to be effective in some vasculitic neuropathy types. PMID:25829955

Overview of pediatric peripheral facial nerve paralysis: analysis of 40 patients.

PubMed

Özkale, Yasemin; Erol, İlknur; Saygı, Semra; Yılmaz, İsmail

2015-02-01

Peripheral facial nerve paralysis in children might be an alarming sign of serious disease such as malignancy, systemic disease, congenital anomalies, trauma, infection, middle ear surgery, and hypertension. The cases of 40 consecutive children and adolescents who were diagnosed with peripheral facial nerve paralysis at Baskent University Adana Hospital Pediatrics and Pediatric Neurology Unit between January 2010 and January 2013 were retrospectively evaluated. We determined that the most common cause was Bell palsy, followed by infection, tumor lesion, and suspected chemotherapy toxicity. We noted that younger patients had generally poorer outcome than older patients regardless of disease etiology. Peripheral facial nerve paralysis has been reported in many countries in America and Europe; however, knowledge about its clinical features, microbiology, neuroimaging, and treatment in Turkey is incomplete. The present study demonstrated that Bell palsy and infection were the most common etiologies of peripheral facial nerve paralysis. © The Author(s) 2014.

Stem cell and peripheral nerve injury and repair.

PubMed

Dong, Ming-min; Yi, Tian-hua

2010-10-01

Peripheral motor nerve injuries are a significant source of morbidity. Neural stem cells (NSCs), a group of relatively primitive cells, possess self-renewal ability and multidifferentiation potential. NSCs may be successfully separated from the human embryo and central nervous system (CNS) and differentiated into mature neurons and gliacytes by in vitro induction or transplantation into the body and may be differentiated into Schwann-like cells under specific conditions. It has been demonstrated that the ability of peripheral nerves to regenerate is mainly attributable to Schwann cells. NSC transplantation can promote peripheral nerve regeneration and provide a new means for treatment of peripheral nerve injury. In recent years, the study of NSCs has become a focus of many laboratories, but the biological characteristics and differentiation regulation mechanisms are not fully clear. In this article, we provide a brief review of NSC characteristics, cultivation, oriented differentiation, and clinical application. © Thieme Medical Publishers.

Necrotizing Fasciitis as a Complication of a Continuous Sciatic Nerve Catheter Using the Lateral Popliteal Approach.

PubMed

Dott, Daltry; Canlas, Christopher; Sobey, Christopher; Obremskey, William; Thomson, Andrew Brian

Necrotizing fasciitis is an infection of the soft tissue that is characterized by rapidly spreading inflammation and subsequent necrosis. It is a rare complication of peripheral nerve blocks. We report a rare case of necrotizing fasciitis after placement of a peripheral nerve catheter. A 58-year-old woman presented for an elective right second metatarsal resection and received a sciatic nerve catheter for postoperative pain control. On postoperative day 7, clinical examination and imaging supported the diagnosis of necrotizing fasciitis. Multiple reports have been published of necrotizing fasciitis after single-shot peripheral nerve block injections, neuraxial anesthesia, and intramuscular injections. This case highlights the potential for the rare complication of necrotizing fasciitis after peripheral nerve catheter placement.

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society--first revision.

PubMed

2010-12-01

A European Federation of Neurological Societies/Peripheral Nerve Society consensus guideline on the definition, investigation, and treatment of multifocal motor neuropathy (MMN) was published in 2006. The aim is to revise this guideline. Disease experts considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed to in an iterative fashion. The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for MMN, investigations to be considered, and principal recommendations for treatment. © 2010 Peripheral Nerve Society.

Peripheral nerve conduits: technology update

PubMed Central

Arslantunali, D; Dursun, T; Yucel, D; Hasirci, N; Hasirci, V

2014-01-01

Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented. PMID:25489251

Vincristine-induced neuropathy in pediatric patients with acute lymphoblastic leukemia in Oman: Frequent autonomic and more severe cranial nerve involvement.

PubMed

Nazir, Hanan F; AlFutaisi, Amna; Zacharia, Mathew; Elshinawy, Mohamed; Mevada, Surekha T; Alrawas, Abdulhakim; Khater, Doaa; Jaju, Deepali; Wali, Yasser

2017-12-01

Vincristine (VCR) induced peripheral neuropathy is a common complication in children with acute lymphoblastic leukemia (ALL). A retrospective data analysis over an interval of 10 years (2006-2016) of all children with ALL seen at Sultan Qaboos University Hospital was carried out. Electronic medical records of eligible patients were reviewed. Patients with clinical evidence of neuropathy and abnormal nerve conduction studies (NCSs) were included in the study. Nineteen (nine females and 10 males) out of 103 pediatric patients developed VCR-related neuropathy, and their age ranged between 2.5 and 14 years. Symptoms started after 2-11 doses of VCR. All 19 patients had documented peripheral neuropathy on NCSs. The autonomic nervous system and cranial nerves affection was relatively common in our patients; two presented with bradycardia, two patients with unexplained tachycardia, and five had abdominal pain and constipation, complicated by typhlitis in two patients. One patient developed unilateral hearing loss. Two patients developed severe life-threatening cranial nerve involvement with bilateral ptosis and recurrent laryngeal nerve involvement presented as vocal cord paralysis, hoarseness of voice, frequent chocking, and aspiration episodes. Peripheral neuropathy was the commonest form of VCR-related neuropathy. Autonomic neuropathy was relatively common in our patients. Cranial neuropathy is a serious side effect of VCR that can be severe, involving multiple cranial nerves and needs prompt recognition and management. Concomitant administration of pyridoxine and pyridostigmine does not seem to protect against further neurological damage in some patients. © 2017 Wiley Periodicals, Inc.

Long-term engraftment, graft-vs.-host disease, and immunologic reconstitution after experimental transplantation of allogeneic peripheral blood cells from G-CSF-treated donors.

PubMed

Pan, L; Bressler, S; Cooke, K R; Krenger, W; Karandikar, M; Ferrara, J L

1996-10-01

Peripheral blood cells (PBPC) are an alternative source of bone marrow for allogeneic transplantation. Reports from recent clinical trials granulocyte colony-stimulating factor (G-CSF)-mobilized PBPC for allogeneic transplantation show incidence and severity of graft-vs.-host disease (GVHD) similar to those observed in conventional bone marrow transplantation (BMT), despite the presence of 10- to 20-fold more T cell in the PBPC inoculum. In the present study, we examined the effects of pretreatment of donors with G-CSF on GVHD, long-term engraftment, and lymphocyte reconstitution in a murine parent-->F1 model (B6.Ly-5a-->B6d2F1) using splenocytes as a source of peripheral progenitor cells. Recipients of splenocytes from G-CSF-treated donors experienced less mortality from acute GVHD and showed sustained weight gain by day 100 after transplantation. At that time, there was no histological evidence od GVHD in either liver or gut. Recipients of splenocytes from G-CSF-treated donors showed complete donor engraftment within 1 month, which was sustained until the end of the observation period. In contrast, recipients of T cell-depleted splenocytes showed slower donor engraftment and persistent donor/host chimerism. In addition, lymphocyte phenotype and function in mice receiving splenocytes from G-CSF-treated donors was significantly restored by day 100 after transplantation. Thus, the use of G-CSF-mobilized PBPC may provide significant advantages to conventional BMT by reducing GVHD without impairing long-term engraftment and immunologic reconstruction.

High Resolution Melting Analysis is Very Useful to Identify BRCA1 c.4964_4982del19 (rs80359876) Founder Calabrian Pathogenic Variant on Peripheral Blood and Buccal Swab DNA.

PubMed

Minucci, Angelo; De Bonis, Maria; De Paolis, Elisa; Gentile, Leonarda; Santonocito, Concetta; Concolino, Paola; Mignone, Flavio; Capoluongo, Ettore

2017-04-01

Detection of pathogenic variants in hereditary breast and ovarian cancer-related breast cancer type 1 and type 2 susceptibility proteins (BRCA1/2) genes is an effective strategy in cancer prevention and treatment. Some ethnic and geographical regions show different BRCA1/2 mutation spectrum and prevalence. In Italy, elucidation of founder effect in BRCA1/2 genes can have an impact on the management of hereditary cancer families on a healthcare system level, making genetic testing more affordable and cost effective in certain regions. The purpose of this paper is to develop a rapid, low-cost, high-throughput single-tube technology for genotyping the Italian founder mutation c.4964_4982del19 (rs80359876) in the BRCA1 gene, starting from peripheral blood and/or buccal swab DNA. Heterozygote samples for c.4964_4982del19 variant were easily and unambiguously identified by the altered shape of the melting curves and were clearly distinguished by a change in melting temperature that differed by approximately 5 °C. The same results were obtained both with DNA from peripheral blood than buccal swab. We provide evidence about application of high-resolution melting analysis (HRMA) in unambiguously genotyping of the founder BRCA1 c.4964_4982del19 variant (rs80359876) in individuals from the Calabria region of Italy. In fact, HRMA was confirmed to be particularly suitable for the identification of BRCA1 c.4964_4982del19 variant, making this approach useful in clinical molecular diagnostics.

Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch

PubMed Central

Anand, P.; Bley, K.

2011-01-01

Summary Topical capsaicin formulations are used for pain management. Safety and modest efficacy of low-concentration capsaicin formulations, which require repeated daily self-administration, are supported by meta-analyses of numerous studies. A high-concentration capsaicin 8% patch (Qutenza™) was recently approved in the EU and USA. A single 60-min application in patients with neuropathic pain produced effective pain relief for up to 12 weeks. Advantages of the high-concentration capsaicin patch include longer duration of effect, patient compliance, and low risk for systemic effects or drug–drug interactions. The mechanism of action of topical capsaicin has been ascribed to depletion of substance P. However, experimental and clinical studies show that depletion of substance P from nociceptors is only a correlate of capsaicin treatment and has little, if any, causative role in pain relief. Rather, topical capsaicin acts in the skin to attenuate cutaneous hypersensitivity and reduce pain by a process best described as ‘defunctionalization’ of nociceptor fibres. Defunctionalization is due to a number of effects that include temporary loss of membrane potential, inability to transport neurotrophic factors leading to altered phenotype, and reversible retraction of epidermal and dermal nerve fibre terminals. Peripheral neuropathic hypersensitivity is mediated by diverse mechanisms, including altered expression of the capsaicin receptor TRPV1 or other key ion channels in affected or intact adjacent peripheral nociceptive nerve fibres, aberrant re-innervation, and collateral sprouting, all of which are defunctionalized by topical capsaicin. Evidence suggests that the utility of topical capsaicin may extend beyond painful peripheral neuropathies. PMID:21852280

Balance and Gait Impairment: Sensor-Based Assessment for Patients With Peripheral Neuropathy.

PubMed

Campbell, Grace; Skubic, Marjorie A

2018-06-01

Individuals with peripheral neuropathy (PN) frequently experience balance and gait impairments that can lead to poor physical function, falls, and injury. Nurses are aware that patients with cancer experience balance and gait impairments but are unsure of optimal assessment and management strategies. This article reviews options for balance and gait assessment for patients diagnosed with cancer experiencing PN, describes advantages and limitations of the various options, and highlights innovative, clinically feasible technologies to improve clinical assessment and management. The literature was reviewed to identify and assess the gold standard quantitative measures for assessing balance and gait. Gold standard quantitative measures are burdensome for patients and not often used in clinical practice. Sensor-based technologies improve balance and gait assessment options by calculating precise impairment measures during performance of simple clinical tests at the point of care.

Factors associated with developing a fear of falling in subjects with primary open-angle glaucoma.

PubMed

Adachi, Sayaka; Yuki, Kenya; Awano-Tanabe, Sachiko; Ono, Takeshi; Shiba, Daisuke; Murata, Hiroshi; Asaoka, Ryo; Tsubota, Kazuo

2018-02-13

To investigate the relationship between clinical risk factors, including visual field (VF) defects and visual acuity, and a fear of falling, among patients with primary open-angle glaucoma (POAG). All participants answered the following question at a baseline ophthalmic examination: Are you afraid of falling? The same question was then answered every 12 months for 3 years. A binocular integrated visual field was calculated by merging a patient's monocular Humphrey field analyzer VFs, using the 'best sensitivity' method. The means of total deviation values in the whole, superior peripheral, superior central, inferior central, and inferior peripheral VFs were calculated. The relationship between these mean VF measurements, and various clinical factors, against patients' baseline fear of falling and future fear of falling was analyzed using multiple logistic regression. Among 392 POAG subjects, 342 patients (87.2%) responded to the fear of falling question at least twice in the 3 years study period. The optimal regression model for patients' baseline fear of falling included age, gender, mean of total deviation values in the inferior peripheral VF and number of previous falls. The optimal regression equation for future fear of falling included age, gender, mean of total deviation values in the inferior peripheral VF and number of previous falls. Defects in the inferior peripheral VF area are significantly related to the development of a fear of falling.

Longitudinal peripheral blood transcriptional analysis of a patient with severe Ebola virus disease.

PubMed

Kash, John C; Walters, Kathie-Anne; Kindrachuk, Jason; Baxter, David; Scherler, Kelsey; Janosko, Krisztina B; Adams, Rick D; Herbert, Andrew S; James, Rebekah M; Stonier, Spencer W; Memoli, Matthew J; Dye, John M; Davey, Richard T; Chertow, Daniel S; Taubenberger, Jeffery K

2017-04-12

The 2013-2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was unprecedented in the number of documented cases, but there have been few published reports on immune responses in clinical cases and their relationships with the course of illness and severity of Ebola virus disease. Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia, fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although experimental treatments are in development, there are no current U.S. Food and Drug Administration-approved vaccines or therapies. We report a detailed study of host gene expression as measured by microarray in daily peripheral blood samples collected from a patient with severe Ebola virus disease. This individual was provided with supportive care without experimental therapies at the National Institutes of Health Clinical Center from before onset of critical illness to recovery. Pearson analysis of daily gene expression signatures revealed marked gene expression changes in peripheral blood leukocytes that correlated with changes in serum and peripheral blood leukocytes, viral load, antibody responses, coagulopathy, multiple organ dysfunction, and then recovery. This study revealed marked shifts in immune and antiviral responses that preceded changes in medical condition, indicating that clearance of replicating Ebola virus from peripheral blood leukocytes is likely important for systemic viral clearance. Copyright © 2017, American Association for the Advancement of Science.

Atherectomy using a solid-state laser at 355 nm wavelength.

PubMed

Herzog, Amir; Oszkinis, Grzegorz; Planer, David; Ziaja, Krzysztof; Kruszyna, Łukasz; Stanisić, Michał Goran; Ziaja, Damian; Ishaaya, Amiel A; Kuczmik, Wacław

2017-10-01

Peripheral arterial disease (PAD), caused by atherosclerotic processes, is allied with an increased risk of ischemic events, limb loss, and death. Recently, the use of a solid-state laser at 355 nm within a hybrid catheter was suggested for that purpose. In this work, short nanosecond pulses of a solid-state laser at 355 nm delivered through a hybrid catheter, composed of optical fibers and a blunt mechanical blade, are used to conduct a pre-clinical study and two clinical cases. The pre-clinical study consisted of an atherosclerotic calcified cadaveric leg and a porcine in vivo trial within the iliac artery, respectively. The clinical cases include chronic total occlusions with a calcified lesion. The occluded cadaveric leg is recanalized successfully and no evidence of thermal necrosis is indicated in the histopathology analysis of the porcine study. No arterial wall damage is demonstrated on the animals' treated arteries and no significant impact on blood count and biochemistry analysis is noted in the animal trial. Successful recanalization of the occluded arteries followed by balloon angioplasty is obtained in both clinical cases. Our work constitutes a proof of concept for using a solid-state pulsed laser at 355 nm in atherectomy. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improving understanding of trigger points and widespread pressure pain sensitivity in tension-type headache patients: clinical implications.

PubMed

Fernández-De-Las-Peñas, César; Arendt-Nielsen, Lars

2017-09-01

The underlying etiology of tension type headache (TTH) is not understood. The current paper highlights the etiologic role of muscle trigger points (TrPs) to the development and maintenance of central sensitization in TTH and its clinical repercussion for proper management of these patients. Areas covered: A literature search on Pub Med for English-language published papers between 1990 and May 2017 to provide the most updated data on the topic was conducted. Current literature suggests that the referred pain elicited by active trigger points (TrPs) contributes to the manifestations of TTH. There is also evidence supporting that TrPs represent a peripheral source of nociception and thereby a driver in the development of central sensitization. In fact, TrPs have been found to be associated with widespread pressure pain sensitivity in TTH. Temporal and spatial summation of TrP nociception suggests that inactivating TrP in the neck, head and shoulder muscles could help these patients; however, current evidence supporting the therapeutic role of TrPs in TTH is conflicting. Expert commentary: Understanding the role of TrPs in TTH in widespread pain sensitization may help to develop better management regimes and possibly prevent TTH from developing into more chronic conditions.

Role of cytokines and treatment algorithms in retinopathy of prematurity.

PubMed

Hartnett, M Elizabeth

2017-05-01

Currently, severe retinopathy of prematurity (ROP) is diagnosed by clinical evaluation and not a laboratory test. Laser is still considered standard care. However, anti-vascular endothelial growth factor (VEGF) agents are being used and there are questions whether and/or if to use them, what dose or type of agent should be considered and what agent may be most beneficial in specific cases. Also unclear are the effects of laser or anti-VEGF on severe ROP, refractive outcomes or infant development. This article reviews recent studies related to these questions and other trials for severe ROP. Imaging studies identify biomarkers of risk (plus disease, stage 3 ROP, and ROP in zone I). Intravitreal bevacizumab or ranibizumab are reported effective in treating aggressive posterior ROP in small series. Recurrences and effects on myopia vary among studies. Use of anti-VEGF agents affects cytokines in the infant blood and reduces systemic VEGF for up to 2 months, raising potential safety concerns. The effects of treatment vary based on infant size and are not comparable. Evidence for most studies is not high. Studies support experimental evidence that inhibiting VEGF reduces stage 3 ROP and peripheral avascular retina. Ongoing large-scale clinical trials may provide clarity for best treatments of severe ROP. Current guidelines hold for screening and treatment for type 1 ROP.

Concordance of vitamin D peripheral levels in infertile couples' partners.

PubMed

Paffoni, Alessio; Ferrari, Stefania; Mangiarini, Alice; Noli, Stefania; Bulfoni, Alessandro; Vigano, Paola; Parazzini, Fabio; Somigliana, Edgardo

2017-08-01

A large number of evidence supports the role of vitamin D insufficiency in both women and men infertility. However, no studies have evaluated the rate of concordance of vitamin D status between the partners. This finding might open new scenarios in the interpretation of the available data linking vitamin D insufficiency and infertility. In the present cross-sectional study, 103 consecutive infertile couples were recruited between April and May 2014. Both partners concomitantly provided a serum sample for the assessment of 25-hydroxy-vitamin D [25-(OH)-D]. Vitamin D insufficiency was defined as serum 25-(OH)-D <20 ng/ml. One hundred-fifty subjects (73 women and 77 males) were 25-(OH)-D insufficient, corresponding to a rate of 73%. Overall, concordance was observed in 73 couples (71%), thus higher than the expected 61% (0.732 + 0.272) based on chance (p = 0.007). The Pearson coefficient of correlation R2 between the partners of the couples was 0.52 (p < 0.001). No statistically significant differences emerged when evaluating the rate of 25-(OH)-D insufficiency according to the causes of infertility. Serum 25-(OH)-D correlates within the partners of infertile couples. Further evidence is warranted to determine the clinical relevance and possible clinical applications of this finding.

Difference of Morphology and Immunophenotype between Central and Peripheral Squamous Cell Carcinomas of the Lung

PubMed Central

Hayashi, Tomayoshi; Sano, Hisao; Egashira, Ryoko; Tabata, Kazuhiro; Tanaka, Tomonori; Kashima, Yukio; Nunomura, Sayuri

2013-01-01

Background. Recent agents, that is, pemetrexed and bevacizumab, have shown reproductive negative association between squamous histology. According to these agents' effectiveness, ruling out of the squamous histology is a significant issue for surgical pathologists. Several articles have proposed the distinction of peripheral type from central type of squamous cell carcinoma (SqCC) due to its similarity to adenocarcinoma, although little evidence to support the difference between these two types was published. In this study, we compared the clinicopathologic findings of central and peripheral pulmonary SqCCs. Material and Methods. 15 central and 35 peripheral types of SqCC from 2005 to 2010 were examined. Twelve morphological features were scored based on their intensity in the original H&E slides, and then, tissue microarray holding triplicated cores from 43 cases was immunohistochemically examined for cytokeratin (CK)7, CK14, TTF-1, Napsin A, p63, CK34βE12, CK5/6, and p53. Result. Most of the histological findings did not separate central and peripheral SqCCs; only the presence of emphysema, interstitial fibrosis, and entrapped pneumocytes inside the tumor showed statistic predominance in peripheral SqCC. This is the first immunophenotypic research in the central and peripheral types of SqCC. PMID:24069587

Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury.

PubMed

Au, Ngan Pan Bennett; Kumar, Gajendra; Asthana, Pallavi; Tin, Chung; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

2016-05-27

Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury.

Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot study of gene expression in peripheral blood.

PubMed

Aspler, Anne L; Bolshin, Carly; Vernon, Suzanne D; Broderick, Gordon

2008-09-26

Genomic profiling of peripheral blood reveals altered immunity in chronic fatigue syndrome (CFS) however interpretation remains challenging without immune demographic context. The object of this work is to identify modulation of specific immune functional components and restructuring of co-expression networks characteristic of CFS using the quantitative genomics of peripheral blood. Gene sets were constructed a priori for CD4+ T cells, CD8+ T cells, CD19+ B cells, CD14+ monocytes and CD16+ neutrophils from published data. A group of 111 women were classified using empiric case definition (U.S. Centers for Disease Control and Prevention) and unsupervised latent cluster analysis (LCA). Microarray profiles of peripheral blood were analyzed for expression of leukocyte-specific gene sets and characteristic changes in co-expression identified from topological evaluation of linear correlation networks. Median expression for a set of 6 genes preferentially up-regulated in CD19+ B cells was significantly lower in CFS (p = 0.01) due mainly to PTPRK and TSPAN3 expression. Although no other gene set was differentially expressed at p < 0.05, patterns of co-expression in each group differed markedly. Significant co-expression of CD14+ monocyte with CD16+ neutrophil (p = 0.01) and CD19+ B cell sets (p = 0.00) characterized CFS and fatigue phenotype groups. Also in CFS was a significant negative correlation between CD8+ and both CD19+ up-regulated (p = 0.02) and NK gene sets (p = 0.08). These patterns were absent in controls. Dissection of blood microarray profiles points to B cell dysfunction with coordinated immune activation supporting persistent inflammation and antibody-mediated NK cell modulation of T cell activity. This has clinical implications as the CD19+ genes identified could provide robust and biologically meaningful basis for the early detection and unambiguous phenotyping of CFS.

Elevated Levels of Peripheral Kynurenine Decrease Bone Strength in Rats with Chronic Kidney Disease

PubMed Central

Kalaska, Bartlomiej; Pawlak, Krystyna; Domaniewski, Tomasz; Oksztulska-Kolanek, Ewa; Znorko, Beata; Roszczenko, Alicja; Rogalska, Joanna; Brzoska, Malgorzata M.; Lipowicz, Pawel; Doroszko, Michal; Pryczynicz, Anna; Pawlak, Dariusz

2017-01-01

The diagnosis and treatment of bone disorders in patients with chronic kidney disease (CKD) represent a clinical challenge. CKD leads to mineral and bone complications starting early in the course of renal failure. Recently, we have observed the positive relationship between intensified central kynurenine turnover and bone strength in rats with subtotal 5/6 nephrectomy (5/6 Nx)-induced CKD. The aim of the present study was to determine the association between peripheral kynurenine pathway metabolites and bone strength in rats with 5/6 Nx-induced CKD. The animals were sacrificed 1 and 3 months after 5/6 Nx or sham operation. Nephrectomized rats presented higher concentrations of serum creatinine, urea nitrogen, and parathyroid hormone both 1 and 3 months after nephrectomy. These animals revealed higher concentrations of kynurenine and 3-hydroxykynurenine in the serum and higher gene expression of aryl hydrocarbon receptor (AhR) as a physiological receptor for kynurenine and AhR-dependent cytochrome in the bone tissue. Furthermore, nephrectomy significantly increased the number of osteoclasts in the bone without affecting their resorptive activity measured in serum. These changes were particularly evident in rats 1 month after 5/6 Nx. The main bone biomechanical parameters of the tibia were unchanged between nephrectomized and sham-operated rats but were significantly increased in older compared to younger animals. A similar trend was observed for geometrical parameters measured with calipers, bone mineral density based on Archimedes' method and image of bone microarchitecture obtained from micro-computed tomography analyses of tibial cortical bone. In nephrectomized animals, peripheral kynurenine levels correlated negatively with the main parameters of bone biomechanics, bone geometry, and bone mineral density values. In conclusion, our data suggest that CKD-induced elevated levels of peripheral kynurenine cause pathological changes in bone structure via AhR pathway. This finding opens new opportunities for the treatment/prevention of osteoporosis in CKD. PMID:29163188

Pericarditis as presenting manifestation of acute nonlymphocytic leukemia in a young child.

PubMed

Chu, J Y; Demello, D; O'Connor, D M; Chen, S C; Gale, G B

1983-07-15

A case of acute nonlymphocytic leukemia presenting as pericarditis is reported in a five-year-old boy. Initially, a clinical diagnosis of viral pericarditis was made, because the child did not demonstrate hematologic or clinical manifestations of leukemia. Acute undifferentiated or lymphocytic leukemia. Acute undifferentiated or lymphocytic leukemia was diagnosed one week after admission when his peripheral blood count became abnormal. The patient did not respond to vincristine and prednisone. When cytochemical evaluation indicated acute myelomonocytic leukemia, employment of cytosine arabinoside and 6-thioguanine was instituted and the child began to improve. Currently, he is still in good remission and has no evidence of recurrence of pericarditis, 1 1/2 years after his initial presentation. In reviewing the literature, we found 17 patients who had leukemic pericardial effusion with cardiac tamponade. There are three reported cases of young children with pericardial effusion as the initial manifestation of acute lymphocytic leukemia, but no reported cases due to nonlymphocytic leukemia, as in this child.