RESUMO
BACKGROUND: The COVID-19 pandemic challenged healthcare systems worldwide and disrupted primary care, particularly prevention, screening, and lifestyle counselling. BETTER WISE is a comprehensive and structured approach that proactively addresses cancer and chronic disease prevention and screening (CCDPS), including cancer survivorship and screening for poverty and lifestyle risks for patients aged 40 to 65. Patients from 13 primary care clinics (urban, rural, and remote) in Alberta, Ontario, and Newfoundland & Labrador, Canada were invited for a 1-hour visit with a prevention practitioner (PP), a member of the primary care team with specialized training in CCDPS to provide patients an overview of eligible screening and assist with lifestyle counselling. This qualitative sub-study describes how the COVID-19 pandemic impacted BETTER WISE in a constantly changing medical landscape. METHODS: We conducted 17 focus groups and 48 key informant interviews with a total of 132 primary care providers (PPs, physicians, allied health professionals, and clinic staff) over three different time points to better understand their perspectives on the BETTER WISE project. We also received 585 patient feedback forms of the 1005 patients who agreed to participate in the study. We also collected field notes and memos and employed thematic analysis using a constant comparative method focused on the impact of the pandemic on BETTER WISE. RESULTS: We identified four themes related to how the COVID-19 pandemic impacted the BETTER WISE study: 1) Switch of in-person visits to visits over the phone; 2) Lack of access to preventive care and delays of screening tests; 3) Changes in primary care providers' availability and priorities; 4) Mental health impacts of the pandemic on patients and primary care providers. CONCLUSIONS: The COVID-19 pandemic had and, at the time of writing, continues to have an impact on primary care, particularly on prevention, screening, and lifestyle counselling. Despite structural, procedural, and personal challenges throughout different waves of the pandemic, the primary care clinics participating in BETTER WISE were able to complete the study. Our results underscore the importance of the role of primary care providers in adapting to changing circumstances and support of patients in these challenging times. TRIAL REGISTRATION: This qualitative study is a sub-component of the BETTER WISE pragmatic, cRCT, trial registration ISRCTN21333761 (date of registration 19/12/2016).
Assuntos
COVID-19 , Humanos , Pandemias , Pesquisa Qualitativa , Grupos Focais , Doença Crônica , AlbertaRESUMO
BACKGROUND: The BETTER (Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Primary Care) intervention was designed to integrate the approach to chronic disease prevention and screening in primary care and demonstrated effective in a previous randomized trial. METHODS: We tested the effectiveness of the BETTER HEALTH intervention, a public health adaptation of BETTER, at improving participation in chronic disease prevention and screening actions for residents of low-income neighbourhoods in a cluster randomized trial, with ten low-income neighbourhoods in Durham Region Ontario randomized to immediate intervention vs. wait-list. The unit of analysis was the individual, and eligible participants were adults age 40-64 years residing in the neighbourhoods. Public health nurses trained as "prevention practitioners" held one prevention-focused visit with each participant. They provided participants with a tailored prevention prescription and supported them to set health-related goals. The primary outcome was a composite index: the number of evidence-based actions achieved at six months as a proportion of those for which participants were eligible at baseline. RESULTS: Of 126 participants (60 in immediate arm; 66 in wait-list arm), 125 were included in analyses (1 participant withdrew consent). In both arms, participants were eligible for a mean of 8.6 actions at baseline. At follow-up, participants in the immediate intervention arm met 64.5% of actions for which they were eligible versus 42.1% in the wait-list arm (rate ratio 1.53 [95% confidence interval 1.22-1.84]). CONCLUSION: Public health nurses using the BETTER HEALTH intervention led to a higher proportion of identified evidence-based prevention and screening actions achieved at six months for people living with socioeconomic disadvantage. TRIAL REGISTRATION: NCT03052959 , registered February 10, 2017.
Assuntos
Programas de Rastreamento , Saúde Pública , Adulto , Doença Crônica , Humanos , Pessoa de Meia-Idade , Ontário , Atenção Primária à SaúdeRESUMO
BACKGROUND: This qualitative study is a sub-component of BETTER WISE, a comprehensive and structured approach that proactively addresses chronic disease prevention, screening, and cancer survivorship, including screening for poverty and addressing lifestyle risks for patients aged 40 to 65. Patients (n = 527) from 13 primary care clinics (urban, rural, and remote) in Alberta, Ontario, and Newfoundland & Labrador, Canada agreed to participate in the study and were invited to a one-hour prevention visit delivered by a Prevention Practitioner (PP) as part of BETTER WISE. We identified the key components of a BETTER WISE prevention visit based on patients' and primary care providers' perspectives. METHODS: Primary care providers (PPs, physicians and their staff) participated in 14 focus groups and 19 key informant interviews to share their perspectives on the BETTER WISE project. Of 527 patients who agreed to participate in the study and were invited for a BETTER WISE prevention visit with a PP, we received 356 patient feedback forms. We also collected field notes and memos and employed thematic analysis using a constant comparative method focusing on the BETTER WISE prevention visit. RESULTS: We identified four key themes related to a BETTER WISE prevention visit: 1) Creating a safe environment and building trust with patients: PPs provided sufficient time and a safe space for patients to share what was important to them, including their concerns related to poverty, alcohol consumption, and mental health, topics that were often not shared with physicians; 2) Providing personalized health education: PPs used the BETTER WISE tools to provide patients with a personalized overview of their health status and eligible screening; 3) Non-judgmental empowering of patients: Instead of directing patients on what to do, PPs evoked patients' preferences and helped them to set goals (if desired); and 4) Integrating care for patients: PPs clarified information from patients' charts and surveys with physicians and helped patients to navigate resources within and outside of the primary care team. CONCLUSIONS: The results of this study underscore the importance of personalized, trusting, non-judgmental, and integrated relationships between primary care providers and patients to effectively address chronic disease prevention, screening, and cancer survivorship as demonstrated by the BETTER WISE prevention visits. TRIAL REGISTRATION: This qualitative study is a sub-component of the BETTER WISE pragmatic, cRCT, trial registration ISRCTN21333761 (date of registration 19/12/2016).
Assuntos
Programas de Rastreamento , Atenção Primária à Saúde , Doença Crônica , Humanos , Ontário , Pesquisa QualitativaRESUMO
BACKGROUND AND OBJECTIVE: Intraoperative hemodynamic stability is essential to safety and post-operative well-being of patients and should be optimized in closed-loop control of anesthesia. Cardiovascular changes inducing variations in pharmacokinetics may require dose modification. Rigorous investigational tools can strengthen current knowledge of the anesthesiologists and support clinical practice. We quantify the cardiovascular response of high-risk patients to closed-loop anesthesia and propose a new application of physiologically-based pharmacokinetic-pharmacodynamic (PBPK-PD) simulations to examine the effect of hemodynamic changes on the depth of hypnosis (DoH). METHODS: We evaluate clinical hemodynamic changes in response to anesthesia induction in high-risk patients from a study on closed-loop anesthesia. We develop and validate a PBPK-PD model to simulate the effect of changes in cardiac output (CO) on plasma levels and DoH. The wavelet-based anesthetic value for central nervous system monitoring index (WAVCNS) is used as clinical end-point of propofol hypnotic effect. RESULTS: The median (interquartile range, IQR) changes in CO and arterial pressure (AP), 3 min after induction of anesthesia, are 22.43 (14.82-36.0) % and 26.60 (22.39-35.33) % respectively. The decrease in heart rate (HR) is less marked, i.e. 8.82 (4.94-12.68) %. The cardiovascular response is comparable or less enhanced than in manual propofol induction studies. PBPK simulations show that the marked decrease in CO coincides with high predicted plasma levels and deep levels of hypnosis, i.e. WAVCNS < 40. PD model identification is improved using the PBPK model rather than a standard three-compartment PK model. PD simulations reveal that a 30% drop in CO can cause a 30% change in WAVCNS. CONCLUSIONS: Significant CO drops produce increased predicted plasma concentrations corresponding to deeper anesthesia, which is potentially dangerous for elderly patients. PBPK-PD model simulations allow studying and quantifying these effects to improve clinical practice.
Assuntos
Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/farmacocinética , Débito Cardíaco , Propofol/administração & dosagem , Propofol/farmacocinética , Idoso , Algoritmos , Anestesia , Vias de Administração de Medicamentos , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Elders living with polypharmacy may be taking medications that do not benefit them. Polypharmacy can be associated with elevated risks of poor health, reduced quality of life, high care costs, and persistently complex care needs. While many medications could be problematic, this project targets medications that should be deprescribed for most elders and for which guidelines and evidence-based deprescribing tools are available. These are termed potentially inappropriate prescriptions (PIPs) and are as follows: proton pump inhibitors, benzodiazepines, antipsychotics, and sulfonylureas. Implementation strategies for deprescribing PIPs in complex older patient populations are needed. METHODS: This will be a pragmatic cluster randomized controlled trial in community-based primary care practices across Canada. Eligible practices provide comprehensive primary care and have at least one physician that consents to participate. Community-dwelling patients aged 65 years and older with ten or more unique medication prescriptions in the past year will be included. The objective is to assess whether the intervention reduces targeted PIPs for these patients compared with usual care. The intervention, Structured Process Informed by Data, Evidence and Research (SPIDER), is a collaboration between quality improvement (QI) and research programs. Primary care teams will form interprofessional Learning Collaboratives and work with QI coaches to review electronic medical record data provided by their regional Practice Based Research Networks (PBRNs), identify areas of improvement, and develop and implement changes. The study will be tested for feasibility in three PBRNs (Toronto, Montreal, and Edmonton) using prospective single-arm mixed methods. Findings will then guide a pragmatic cluster randomized controlled trial in five PBRNs (Calgary, Winnipeg, Ottawa, Montreal, and Halifax). Seven practices per PBRN will be recruited for each arm. The analysis will be by intention to treat. Ten percent of patients who have at least one PIP at baseline will be randomly selected to participate in the assessment of patient experience and self-reported outcomes. Qualitative methods will be used to explore patient and physician experience and evaluate SPIDER's processes. CONCLUSION: We are testing SPIDER in a primary care population with complex care needs. This could provide a widely applicable model for care improvement. TRIAL REGISTRATION: Clinicaltrials.gov NCT03689049 ; registered September 28, 2018.
Assuntos
Polimedicação , Atenção Primária à Saúde/normas , Melhoria de Qualidade , Idoso , Idoso de 80 Anos ou mais , Canadá , Humanos , Prescrição Inadequada , Masculino , Qualidade de Vida , Projetos de PesquisaRESUMO
INTRODUCTION: Electronic medical record (EMR) databases have become increasingly popular for secondary purposes, such as health research. The Canadian Primary Care Sentinel Surveillance Network (CPCSSN) is the first and only pan-Canadian primary care EMR data repository, with de-identified health information for almost two million Canadians. Comprehensive and freely available documentation describing the data 'lifecycle' is important for assessing potential data quality issues and appropriate interpretation of research findings. Here, we describe the flow and transformation of CPCSSN data in the province of Alberta. APPROACH: In Alberta, the data originate from 54 publicly-funded primary care settings, including one community pediatric clinic, with 318 providers contributing de-identified EMR data for 410,951 patients (as of December 2018). Data extraction methods have been developed for five different EMR systems, and include both backend and automated frontend extractions. The raw EMR data are transformed according to specific rules, including trimming implausible values, converting values and free text to standard terminologies or classification systems, and structuring the data into a common CPCSSN format. Following local data extraction and processing, the data are transferred to a central repository and made available for research and disease surveillance. CONCLUSION: This paper aims to provide important contextual information to future CPCSSN data users.
RESUMO
BACKGROUND: Currently, the specific role of family physicians (fps) in the care of people with cancer is not well defined. Our goal was to explore physician perspectives and contextual factors related to the coordination of cancer care and the role of fps. METHODS: Using a constructivist grounded theory approach, we conducted telephone interviews with 58 primary and cancer specialist health care providers from across Canada. RESULTS: The participants-21 fps, 15 surgeons, 12 medical oncologists, 6 radiation oncologists, and 4 general practitioners in oncology-were asked to describe both the role that fps currently play and the role that, in their opinion, fps should play in the future care of cancer patients across the cancer continuum. Participants identified 3 key roles: coordinating cancer care, managing comorbidities, and providing psychosocial care to patients and their families. However, fps and specialists discussed many challenges that prevent fps from fully performing those roles: â The fps described communication problems resulting from not being kept "in the loop" because they weren't copied on patient reports and also the lack of clearly defined roles for all the various health care providers involved in providing care to cancer patients.â The specialists expressed concerns about a lack of patient access to fp care, leaving specialists to fill the care gaps. The fps and specialists both recommended additional training and education for fps in survivorship care, cancer screening, genetic testing, and new cancer treatments. CONCLUSIONS: Better communication, more collaboration, and further education are needed to enhance the role of fps in the care of cancer patients.
RESUMO
BACKGROUND: Family physicians (fps) play a role in aspects of personalized medicine in cancer, including assessment of increased risk because of family history. Little is known about the potential role of fps in supporting cancer patients who undergo tumour gene expression profile (gep) testing. METHODS: We conducted a mixed-methods study with qualitative and quantitative components. Qualitative data from focus groups and interviews with fps and cancer specialists about the role of fps in breast cancer gep testing were obtained during studies conducted within the pan-Canadian canimpact research program. We determined the number of visits by breast cancer patients to a fp between the first medical oncology visit and the start of chemotherapy, a period when patients might be considering results of gep testing. RESULTS: The fps and cancer specialists felt that ordering gep tests and explaining the results was the role of the oncologist. A new fp role was identified relating to the fp-patient relationship: supporting patients in making adjuvant therapy decisions informed by gep tests by considering the patient's comorbid conditions, social situation, and preferences. Lack of fp knowledge and resources, and challenges in fp-oncologist communication were seen as significant barriers to that role. Between 28% and 38% of patients visited a fp between the first oncology visit and the start of chemotherapy. CONCLUSIONS: Our findings suggest an emerging role for fps in supporting patients who are making adjuvant treatment decisions after receiving the results of gep testing. For success in this new role, education and point-of-care tools, together with more effective communication strategies between fps and oncologists, are needed.
RESUMO
The aim of this study was to evaluate fixation stability using two different fixation targets with the Nidek MP1 microperimeter. Twenty-nine healthy subjects with a mean age of 26.53 ± 7.35 years and visual acuity ≥0.0 logMAR were enrolled in this study. Fifty-eight eyes of 29 patients without ophthalmic and/or systemic disease underwent a fixation test with the MP1 microperimeter. Fixation stability related to a red cross (central) and/or a red circle (pericentral) target was quantified using either Fujii classification or by calculating the bivariate contour ellipse area (BCEA). For statistical analysis, BCEA values were converted into their logarithms (logBCEA) and all data obtained were analyzed using paired Student's t test. The inclination values of the axis of BCEA were analyzed with Chi squared test. The mean values of logBCEA and the mean values of the major and minor axis of the ellipses related to the cross and the circle fixation target were significantly different (68.2 %, p = 0.00; 95.4 %, p = 0.00; 99.6 %, p = 0.00, respectively) for each BCEA standard deviation. Fixation was significantly less stable for the pericentral fixation target in normal subjects, indicating an advantage for central fixation targets. These results are of particular interest when evaluation of changes in fixation is needed.
Assuntos
Fixação Ocular/fisiologia , Testes de Campo Visual/métodos , Campos Visuais/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Acuidade Visual , Adulto JovemRESUMO
A new project was recently initiated for the realization of the "Land Unit and Soil Capability Map of Sardinia" at a scale of 1:50,000 to support land use planning. In this study, we outline the general structure of the project and the methods used in the activities that have been thus far conducted. A GIS approach was used. We used the soil-landscape paradigm for the prediction of soil classes and their spatial distribution or the prediction of soil properties based on landscape features. The work is divided into two main phases. In the first phase, the available digital data on land cover, geology and topography were processed and classified according to their influence on weathering processes and soil properties. The methods used in the interpretation are based on consolidated and generalized knowledge about the influence of geology, topography and land cover on soil properties. The existing soil data (areal and point data) were collected, reviewed, validated and standardized according to international and national guidelines. Point data considered to be usable were input into a specific database created for the project. Using expert interpretation, all digital data were merged to produce a first draft of the Land Unit Map. During the second phase, this map will be implemented with the existing soil data and verified in the field if also needed with new soil data collection, and the final Land Unit Map will be produced. The Land Unit and Soil Capability Map will be produced by classifying the land units using a reference matching table of land capability classes created for this project.
Assuntos
Bases de Dados Factuais , Sistemas de Informação Geográfica , Solo , Fenômenos Geológicos , ItáliaRESUMO
Supraventricular tachycardia (SVT), being atrioventricular reentry the underlying mechanism, is the most frequently tachyarrhythmia requiring a medical treatment in infants with no cardiac disease. The acute treatment of a single episode of SVT has generally an excellent prognosis. An antiarrhythmic prophylaxis of SVT recurrences is usually recommended during the first year of life. Although many efficient drugs are available for the SVT treatment, a careful risk-benefit analysis of each single case should suggest the correct drug choice.
Assuntos
Antiarrítmicos/uso terapêutico , Comportamento de Escolha , Tomada de Decisões , Taquicardia Supraventricular/congênito , Taquicardia Supraventricular/tratamento farmacológico , Antiarrítmicos/administração & dosagem , Antiarrítmicos/efeitos adversos , Quimioprevenção/métodos , Relação Dose-Resposta a Droga , Humanos , Recém-Nascido , Medição de RiscoRESUMO
A retrospective study to detect specific Y chromosome microdeletions and to evaluate sperm ultrastructural characteristics in infertile men was set up. We selected 219 infertile men referred to Regional Referral Center for Male Infertility, Siena, Italy for semen analysis from January 1999 to April 2004. Family history, lymphocyte karyotype determination, Y microdeletion screening, physical examination, hormonal assays, semen analysis were carried out. Sperm concentration and progressive motility, ultrastructural analysis of sperm organelles, PCR amplification of sequence tagged sites for Y microdeletion screening were performed. Different Y-chromosome deletions were found, mainly in the AZFb and AZFc regions. Severe alterations of sperm ultrastructure, affecting whole sperm population, were detected in carriers of Y-deletions. Our data confirms the highest frequency of Y deletions in azoospermic patients. In all other patients with Y microdeletions, sperm ultrastructural defects affected the whole sperm population and were mainly related to apoptosis or immaturity.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Y/genética , Infertilidade Masculina/genética , Espermatozoides/ultraestrutura , Adolescente , Adulto , Humanos , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatozoides/fisiologiaRESUMO
OBJECTIVE: This study investigated the in vitro effects of hyaluronic acid (HA) of molecular weight (MW) 500-730 kDa on human articular chondrocytes cultivated for 48 h in the presence of interleukin-1beta (IL-1beta) with and without hydrostatic cyclical pressure. DESIGN: The effects of 10 and 100 microg/ml HA with and without IL-1beta were assessed in the culture medium of cells exposed to pressurization cycles in the form of sinusoidal waves (minimum pressure 1MPa, maximum pressure 5MPa) at a frequency of 0.25Hz for 3h, by the immunoenzymatic method on microplates for the quantitative measurement of human proteoglycans (PG) and by the Griess method for nitrites (NO). Morphological analyses were performed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). RESULTS: The presence of IL-1beta determines a significant decrease in PG and a significant increase in NO concentrations measured in the culture medium. When the cells are cultured in the presence of IL-1beta and HA at the two concentrations, a statistically significant restoration of PG and a decrease in NO levels are observed. Under pressurization conditions, we observed that the PG concentration in the medium of cells presented a very significant increase in all the conditions used in the study, except for IL-1beta alone. NO production decreased very significantly in the presence of IL-1beta+HA 10 and IL-1beta+HA 100. The results of metabolic evaluation are confirmed by morphological findings obtained by TEM and SEM. CONCLUSIONS: These in vitro studies confirm both the protective role of HA (MW 500-730 kDa), which counteracts the IL-1beta-induced effects, and the importance of pressure on chondrocyte metabolism and morphology.
Assuntos
Adjuvantes Imunológicos/farmacologia , Cartilagem Articular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Ácido Hialurônico/farmacologia , Óxido Nítrico/biossíntese , Osteoartrite do Joelho/metabolismo , Proteoglicanas/biossíntese , Idoso , Cartilagem Articular/patologia , Células Cultivadas , Condrócitos/metabolismo , Condrócitos/patologia , Meios de Cultura , Relação Dose-Resposta a Droga , Humanos , Pressão Hidrostática , Interleucina-1/farmacologia , Microscopia Eletrônica/métodos , Microscopia Eletrônica de Varredura/métodos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Asthenozoospermia may sometimes be related to genetic structural defects of the sperm tail detectable by transmission electron microscopy. Dysplasia of the fibrous sheath (DFS) is a genetic sperm defect, characterized by dysplastic development of the axonemal and periaxonemal cytoskeleton. We report the case of an infertile man with normal sperm count and total sperm immotility in which dysplasia of the fibrous sheath, Akap3, Akap4 gene deletions, meiotic segregation of chromosomes 18, X and Y and Y microdeletions were investigated. METHODS: A 32-year-old man with a 3-year history of primary infertility presented at our Regional Referral Center for Male Infertility. Family medical history, lymphocyte karyotype, PCR analysis, physical examination, hormone assays and semen analysis were performed. RESULTS: Ultrastructural sperm evaluation showed dysplasia of the fibrous sheath. Immunostaining of AKAP4 protein was negative in sperm tails. PCR analysis revealed intragenic deletions of the Akap3 and Akap4 genes. Fluorescence in situ hybridization on sperm showed a high frequency of XY disomy. CONCLUSION: In this infertile patient, our results suggest a possible relationship between dysplasia of the fibrous sheath, partial deletions in the Akap3 and Akap4 genes and absence of AKAP4 protein in the fibrous sheath. These findings, however, were not detected in another four patients with dysplasia of the fibrous sheath. Our results require future confirmatory molecular analyses.
Assuntos
Deleção de Genes , Infertilidade Masculina/genética , Espermatozoides/patologia , Espermatozoides/ultraestrutura , Proteínas de Ancoragem à Quinase A , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Cromossomos Humanos Par 18/ultraestrutura , Cromossomos Humanos X/ultraestrutura , Cromossomos Humanos Y/ultraestrutura , Primers do DNA/química , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Meiose , Microscopia Eletrônica , Microscopia de Fluorescência , Oligospermia/diagnóstico , Oligospermia/genética , Reação em Cadeia da Polimerase , Precursores de Proteínas/genética , Raios UltravioletaRESUMO
We report the case of a patient who developed notalgia paresthetica during the recovery from a neuralgic amyotrophy. A 23-year-old woman had a typical neuralgic amyotrophy (severe shoulder pain, followed by a long thoracic nerve palsy); five months after the onset of pain, when scapular winging was improving, she began to feel a burning sensation in a restricted interscapular area, on the same side. Electromyography was consistent with a long thoracic nerve neuropathy, with minor neurogenic changes in deltoid and biceps brachii. Radiography of the spine was unremarkable. The notalgia paresthetica disappeared shortly before the complete recovery of scapular winging. The abnormal activation of shoulder girdle and spine extensor muscles during the time of long thoracic nerve palsy may explain the association between the two disorders.
Assuntos
Neurite do Plexo Braquial/complicações , Ombro/patologia , Adulto , Eletromiografia , Feminino , Humanos , Parestesia/complicações , Escápula/patologiaRESUMO
OBJECTIVES: Patients with peripheral facial palsy (PFP) may present with transient hyperkinetic movement disorders in the side contralateral to the paralysis. One possible cause of such enhanced motor activity is sensitization of reflex responses to afferent inputs from the unprotected cornea. We hypothesized that if this sensitization occurs, the size of the orbicularis oculi (OOc) responses induced by afferents from the ophthalmic branch of the paralyzed side would be larger than those induced by afferents from the contralateral side. METHODS: In 68 patients with complete PFP and in a group of 30 age-matched control subjects we recorded the response of the OOc muscle of one side to electrical stimulation of the supraorbital nerve of both sides, and calculated the ratio between R2c and R2 (R2c/R2). RESULTS: The mean R2c/R2 ratio was significantly larger in patients than in control subjects (unpaired t test, P<0.05). Larger R2c than R2 responses were observed in 23.1% of control subjects and in 80.9% of patients (chi(2)=13.3, P<0.01). CONCLUSIONS: Our results suggest that patients with PFP have an enhanced blink reflex gain to inputs from the paralyzed side compared to those of the non-paralyzed side. Sensitization of the blink reflex polysynaptic pathways to inputs carried by afferent fibers from the ophthalmic branch of the paralyzed side can play a role in inducing an abnormal facial motor behavior after PFP.
Assuntos
Paralisia de Bell/fisiopatologia , Piscadela/fisiologia , Neurônios Aferentes/fisiologia , Órbita/inervação , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Órbita/fisiologia , Paralisia/fisiopatologiaRESUMO
OBJECTIVES: Patients with primary palmar hyperhidrosis (PPH) might exhibit hyperexcitability of the reflex circuits involved in sweating. We hypothesized that this hyperexcitability could become evident in the study of the excitability recovery curve of the sympathetic sudomotor skin response (SSR). METHODS: In 10 patients with PPH and 10 healthy volunteers used as control subjects, we recorded the SSR in the palm of the right hand to pairs of median nerve electrical shocks separated by inter-stimuli intervals (ISIs) ranging from 0.5 to 3.5 s. The amplitude of the SSR generated by the second stimulus (SSR2) was expressed as a percentage of that generated by the first (SSR1), and compared between control subjects and patients for each ISI. RESULTS: None of the control subjects showed a recovery of the SSR for ISIs of 1.5 s or less. On the contrary, patients showed a statistically significant enhancement of the SSR excitability recovery curve, with onset of recovery at 1.5 s in 5 patients. Two patients showed a double peak response to single electrical stimulation and were not considered in the calculation of the SSR recovery curve. Mean excitability recovery percentages were larger in patients than in control subjects at ISIs of 2, 2.5 and 3 s. CONCLUSIONS: The enhancement of the SSR recovery curve in patients with PPH suggests hyperexcitability of the somatosympathetic polisynaptic pathway involved in sweating. This could partly underlie the pathophysiology of PPH.
Assuntos
Hiperidrose/fisiopatologia , Fenômenos Fisiológicos da Pele , Sistema Nervoso Simpático/fisiologia , Adulto , Análise de Variância , Estimulação Elétrica , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Reação/fisiologiaRESUMO
The acrosome, a complex organelle, plays a key regulatory role in the sperm-egg interaction. We have previously shown that ascorbic acid affects both motility and spectrin protein patterns in sperm. In this study, we further characterized the changes in spectrin in sperm challenged with ascorbic acid, using SDS-PAGE, western blots, and immunofluorescence. Ascorbic acid shifts spectrin to a higher-molecular-weight species based on western blot studies. This shift in the spectrin band correlates with a striking series of changes in spectrin immunofluorescence patterns. Upon ascorbic acid challenge, spectrin localization changes, eventually resulting in the formation of vesicles. These vesicles can reach sizes up to five times the original volume of the sperm cell and sometimes show multiple spikes. These findings indicate that a novel process is taking place in the acrosome upon ascorbic acid challenge and suggest that the cytoskeleton may be a useful target for studying and hopefully controlling the sperm-egg interaction.
Assuntos
Acrossomo/metabolismo , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Espectrina/metabolismo , Acrossomo/efeitos dos fármacos , Animais , Bovinos , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Eletroforese em Gel de Poliacrilamida , Imunofluorescência , Masculino , Espectrina/análiseRESUMO
Diphenylhydantoic acid (DPHA) is a degradation product in parenteral formulations of the anticonvulsant phenytoin and the prodrug fosphenytoin. DPHA has also been reported to be a minor metabolite of phenytoin. Levels found in the urine of various species, including humans, after oral or intravenous (iv) phenytoin ranged from undetected to a few percent of administered dose. In the present analysis, the toxicologic profile of DPHA was integrated with exposure data in order to characterize its safety under recommended clinical regimens of fosphenytoin administration. In preclinical safety studies, DPHA was without effect in the Ames assay and at concentrations up to 3000 microg/plate in the presence or absence of metabolic activation, and in the in vitro micronucleus test with acute and 2-week repeated dose studies in Wistar rats at iv doses up to 15 mg/kg. In 4-week studies conducted in rats and dogs receiving fosphenytoin containing DPHA levels up to 1.1%, and in an in vitro structural chromosome aberration test with DPHA levels up to 2.0%, all findings were consistent with known effects of phenytoin (such as CNS signs and increased liver weight), and none were attributed to DPHA. Reports in the literature indicate that in murine in vivo and in vitro models, DPHA has much lower potential for reproductive toxicity than phenytoin. A no-observed-effect level (NOEL) of 15 mg/kg established from the 2-week study in rats was used with probabilistic techniques to estimate tolerable daily doses (TDDs) of DPHA. In this approach, interspecies correction was performed by allometrically scaling the NOEL based on a distributional power of body weight while intraindividual variability was accounted for by selecting the lower percentiles of the population-based distribution of TDDs. The results indicate that a DPHA content limit of 3.0% in an administered dose of fosphenytoin is unlikely to cause adverse effects in patients.