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2.
BJOG ; 128(12): 2034-2043, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34047446

RESUMO

OBJECTIVE: To compare clinical characteristics and outcomes in patients undergoing excision of polypropylene urogynaecological mesh for pain, mesh exposure or both. DESIGN: Prospective, longitudinal cohort. SETTING: Academic tertiary referral centre. POPULATION: Women undergoing complete vaginal mesh excision for mesh exposure and/or pain. METHODS: Clinical and patient-reported outcomes assessing pain (visual analog scale, VAS), bother (Pelvic Floor Distress Inventory, PFDI) and functional impact (Pelvic Functional Impact Questionnaire, PFIQ) were collected at baseline, 6, 12 and 24 months after complete mesh excision. Outcomes were compared by mesh type (sling, prolapse [transvaginal or sacrocolpopexy mesh], both) and complication (pain, exposure, both). MAIN OUTCOME MEASURES: 'Much better' or 'Very much better' on Patient Global Impression of Improvement (PGI-I) up to 2 years after removal. RESULTS: Of 173 women, 48 underwent removal for pain, 27 for exposure and 98 for exposure plus pain. 'Moderate to severe' baseline symptoms were reported by 75%; the most prevalent and severe symptom was dyspareunia. Patients with pain alone were most bothered (PFDI median 234.2, interquartile range 83, P = 0.02) and had the highest functional impact (PFIQ median 181, interquartile range 138, P < 0.001). After excision, only 33.3% of women with pain alone reported 'improved' symptoms (PGI-I), versus 73.9% with exposure, 58.3% with exposure plus pain (P = 0.03) with no differences in PGI-I by mesh type. VAS scores decreased in all groups, but PFDI and PFIQ did not improve in pain patients. CONCLUSIONS: In women experiencing a pain complication after urogynaecological mesh insertion, mesh removal often does not improve symptoms. TWEETABLE ABSTRACT: Only 33% of women with pain complications have improved symptoms after urogynaecological mesh removal.


Assuntos
Remoção de Dispositivo/métodos , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Dor Pós-Operatória/cirurgia , Telas Cirúrgicas/efeitos adversos , Vagina/cirurgia , Idoso , Dispareunia/etiologia , Feminino , Procedimentos Cirúrgicos em Ginecologia/instrumentação , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/etiologia , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Prolapso de Órgão Pélvico/cirurgia , Polipropilenos , Estudos Prospectivos , Resultado do Tratamento , Vagina/patologia
4.
Br J Anaesth ; 121(1): 38-44, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29935592

RESUMO

BACKGROUND: The Standardising Endpoints for Perioperative Medicine group was established to derive an appropriate set of endpoints for use in clinical trials related to anaesthesia and perioperative medicine. Anaesthetic or analgesic technique during cancer surgery with curative intent may influence the risk of recurrence or metastasis. However, given the current equipoise in the existing literature, prospective, randomised, controlled trials are necessary to test this hypothesis. As such, a cancer subgroup was formed to derive endpoints related to research in onco-anaesthesia based on a current evidence base, international consensus and expert guidance. METHODS: We undertook a systematic review to identify measures of oncological outcome used in the oncological, surgical, and wider literature. A multiround Delphi consensus process that included up to 89 clinician-researchers was then used to refine a recommended list of endpoints. RESULTS: We identified 90 studies in a literature search, which were the basis for a preliminary list of nine outcome measures and their definitions. A further two were added during the Delphi process. Response rates for Delphi rounds one, two, and three were 88% (n=9), 82% (n=73), and 100% (n=10), respectively. A final list of 10 defined endpoints was refined and developed, of which six secured approval by ≥70% of the group: cancer health related quality of life, days alive and out of hospital at 90 days, time to tumour progression, disease-free survival, cancer-specific survival, and overall survival (and 5-yr overall survival). CONCLUSION: Standardised endpoints in clinical outcomes studies will support benchmarking and pooling (meta-analysis) of trials. It is therefore recommended that one or more of these consensus-derived endpoints should be considered for inclusion in clinical trials evaluating a causal effect of anaesthesia-analgesia technique on oncological outcomes.


Assuntos
Determinação de Ponto Final/normas , Neoplasias/cirurgia , Assistência Perioperatória/normas , Cuidados Pós-Operatórios/normas , Consenso , Intervalo Livre de Doença , Humanos , Análise de Sobrevida , Resultado do Tratamento
5.
Br J Anaesth ; 116(6): 770-83, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27199310

RESUMO

BACKGROUND: Improvement of postoperative pain and other perioperative outcomes remain a significant challenge and a matter of debate among perioperative clinicians. This systematic review aims to evaluate the effects of perioperative i.v. lidocaine infusion on postoperative pain and recovery in patients undergoing various surgical procedures. METHODS: CENTRAL, MEDLINE, EMBASE, and CINAHL databases and ClinicalTrials.gov, and congress proceedings were searched for randomized controlled trials until May 2014, that compared patients who did or did not receive continuous perioperative i.v. lidocaine infusion. RESULTS: Forty-five trials (2802 participants) were included. Meta-analysis suggested that lidocaine reduced postoperative pain (visual analogue scale, 0 to 10 cm) at 1-4 h (MD -0.84, 95% CI -1.10 to -0.59) and at 24 h (MD -0.34, 95% CI -0.57 to -0.11) after surgery, but not at 48 h (MD -0.22, 95% CI -0.47 to 0.03). Subgroup analysis and trial sequential analysis suggested pain reduction for patients undergoing laparoscopic abdominal surgery or open abdominal surgery, but not for patients undergoing other surgeries. There was limited evidence of positive effects of lidocaine on postoperative gastrointestinal recovery, opioid requirements, postoperative nausea and vomiting, and length of hospital stay. There were limited data available on the effect of systemic lidocaine on adverse effects or surgical complications. Quality of evidence was limited as a result of inconsistency (heterogeneity) and indirectness (small studies). CONCLUSIONS: There is limited evidence suggesting that i.v. lidocaine may be a useful adjuvant during general anaesthesia because of its beneficial impact on several outcomes after surgery.


Assuntos
Anestésicos Locais/efeitos adversos , Anestésicos Locais/uso terapêutico , Lidocaína/efeitos adversos , Lidocaína/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Período de Recuperação da Anestesia , Humanos , Tempo de Internação
6.
Artigo em Inglês | MEDLINE | ID: mdl-29868212

RESUMO

BACKGROUND: Type 2 diabetes mellitus constitutes a global epidemic and a major burden on health care systems across the world. Prevention of this disease is essential, and the development of effective prevention strategies requires validated information on the disease burden and the risk factors. Embarking on a nationally representative cross-sectional study is challenging and costly. Few countries undertake this process regularly, if at all. METHOD: This paper sets out the evidence-based protocol of a recent cross-sectional study that was conducted in Malta. Data collection took place from November 2014 to January 2016. RESULTS: This study presents up-to-date national data on diabetes and its risk factors (such as obesity, smoking, physical activity and alcohol intake) that will soon be publicly available. CONCLUSION: This protocol was compiled so that the study can be replicated in other countries. The protocol contains step-by-step descriptions of the study design, including details on the population sampling, the permissions required and the validated measurement tools used.

7.
Knee Surg Sports Traumatol Arthrosc ; 23(12): 3614-22, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25173508

RESUMO

PURPOSE: Anterior cruciate ligament (ACL) rupture is the most common complete ligamentous injury in the knee. Many studies explored ACL graft integration and maturation, but only a few assessed the application of platelet rich fibrin matrix (PRFM) as augmentation for ACL reconstruction. The main aim of this study was to test the PRFM augmentation in terms of graft-bone integration and knee stability. The secondary aim was to investigate patient-reported functional status. METHODS: Prospective evaluation has been done in two consecutive series of patients who underwent ACL reconstruction with semitendinosus and gracilis (STG) grafts: 14 patients were operated with PRFM augmentation and 14 patients without PRFM augmentation. Objective clinical evaluation (Rolimeter) and MRI evaluation were performed at 1 year from surgery. Subjective evaluation (IKDC) was performed pre-operatively and at 6 months, 1 and 2 years from surgery. RESULTS: A statistically significant difference was not detected between the two groups in terms of MRI and objective clinical evaluation, although PRFM-augmented patients showed a statistically significant higher clinical improvement. CONCLUSIONS: The procedure described for PRFM augmentation in ACL STG reconstruction does not improve radiologic graft integration and knee stability after 1 year and should not be used by clinicians to this purpose. However, it may result in a short-term improvement of patient-reported knee function, and future research should focus on further developing PRP treatment to optimize ACL clinical outcome. LEVEL OF EVIDENCE: III.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior/métodos , Ligamento Cruzado Anterior/cirurgia , Fibrina , Traumatismos do Joelho/cirurgia , Plasma Rico em Plaquetas , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Instabilidade Articular/fisiopatologia , Articulação do Joelho/patologia , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ruptura
8.
Clin Radiol ; 68(10): 1065-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23810694

RESUMO

AIM: To describe the initial pilot phase of the 2009 Scottish Audit of Surgical Mortality (SASM), which includes outcomes and difficulties that arose during any interventional radiology (IR) procedure performed on patients in this audit over an 18 month period. MATERIALS AND METHODS: Approximately 40 consultant interventional radiologists from all units in Scotland elected to participate in the audit. Each response was then peer reviewed after anonymisation of the patient and institution. If a relevant ACON (area for consideration or area of concern) was generated, this was checked by one of the other reviewers before communication with the original reporting radiologist and colleagues. There was then a right of reply by the reporting unit before formal documentation was sent out. RESULTS: Initial results were analysed after 18 months period, during which time 95 forms relating to deaths of surgical inpatients were sent to interventional radiologists identified as having been involved in an IR procedure at some time during the patient's admission. Seventy-one forms had been returned by July 2010, of which 46 had gone through the entire SASM process. From these, 10 ACONs were attributed. Anonymised case vignettes and reports from these were used as educational tools. CONCLUSION: Involvement with SASM is a useful process. Significant safety issues and learning points were identified in the pilot. The majority of ACONs identified by the audit were in patients who had undergone percutaneous biliary interventions.


Assuntos
Radiografia Intervencionista/mortalidade , Procedimentos Cirúrgicos Operatórios/mortalidade , Feminino , Humanos , Masculino , Projetos Piloto , Escócia/epidemiologia
9.
Musculoskelet Surg ; 95 Suppl 1: S49-54, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21503723

RESUMO

Proximal humeral fractures were managed with primary hemiarthroplasty in 57 patients, 53 women (93%) and 4 men (7%) aged 51-87 years (mean 72.2). The mean follow-up period was 52 months (range 12-98), and the mean Constant score was 59.2 (range 38-76). Patients were very satisfied (n = 19); satisfied (n = 32) or dissatisfied with the outcome (n = 5). One patient required early revision surgery. Surgical treatment of three- and four-part fractures of the proximal humerus with hemiarthroplasty is a safe and effective approach, the outcome of which appears to be related to the quality of the anatomical reconstruction of the tuberosities.


Assuntos
Artroplastia de Substituição , Prótese Articular , Fraturas do Ombro/cirurgia , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Substituição/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Br J Anaesth ; 104(4): 490-5, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20167584

RESUMO

BACKGROUND: The aim of this study was to determine whether the ED(50) dose of bupivacaine 0.5% for supraclavicular brachial plexus block increases with increasing body mass index (BMI). METHODS: This double-blind, non-randomized trial followed an up-and-down sequential allocation design. Adult patients undergoing elective upper limb surgery under ultrasound-guided supraclavicular brachial block were recruited. A preliminary study was used to guide the dosing schedule for the main study in which patients were divided into three groups according to their BMI (Group A, BMI >27 kg m(-2); Group B, BMI 24-27 kg m(-2); Group C, BMI <24 kg m(-2)). The study design and analysis followed Dixon's small sample model using a 'nominal' sample size of six per group. RESULTS: Twenty-one patients were recruited to the preliminary study. Using isotonic regression, the ED(50) for bupivacaine 0.5% was estimated to be 8.9 ml [95% confidence interval (CI) 7.8-15.9]. In comparison, the ED(50) volume was found to be 10.8 ml (95% CI 5.9-19.7) using the Dixon-Massey formula. In the main study, six patients were recruited in each group with mean (range) BMI of 31.5 (27.2-38.8) kg m(-2) in Group A, 25.6 (24.4-26.3) kg m(-2) in Group B, and 21.6 (19.7-23.8) kg m(-2) in Group C. The ED(50) (95% CI) for Groups A, B, and C were 8.9 (6.2-12.7), 10.7 (7.5-15.4), and 13.4 (9.3-19.1) ml, respectively (P=0.05 for Group A vs Group C). CONCLUSIONS: Our study demonstrates that the ED(50) of bupivacaine 0.5% does not increase with an increase in BMI. We found evidence of a possible inverse relationship between ED(50) and BMI.


Assuntos
Anestésicos Locais/administração & dosagem , Índice de Massa Corporal , Plexo Braquial/efeitos dos fármacos , Bupivacaína/administração & dosagem , Bloqueio Nervoso/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestésicos Locais/farmacologia , Plexo Braquial/ultraestrutura , Bupivacaína/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ultrassonografia de Intervenção , Extremidade Superior/cirurgia
11.
Cochrane Database Syst Rev ; (4): CD003006, 2005 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-16235310

RESUMO

BACKGROUND: Spinal anaesthesia has been in use since the turn of the late nineteenth century. During the last decade there has been an increase in the number of reports implicating lidocaine as a possible cause of temporary and permanent neurologic complications after spinal anaesthesia. Follow-up of patients who received uncomplicated spinal anaesthesia revealed that some of them developed pain in the lower extremities after an initial full recovery. This painful condition that occurs in the immediate postoperative period was named "transient neurologic symptoms" (TNS). OBJECTIVES: To study the frequency of TNS and neurologic complications after spinal anaesthesia with lidocaine, compared to other local anaesthetics. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (CENTRAL), (The Cochrane Library, Issue 1, 2005); MEDLINE (1966 to January 2005); EMBASE (1980 to week 6, 2005); LILACS (March 2005); and handsearched the reference lists of trials and review articles. SELECTION CRITERIA: We included all randomized and pseudo-randomized studies comparing the frequency of TNS and of neurologic complications after spinal anaesthesia with lidocaine as compared to other local anaesthetics. DATA COLLECTION AND ANALYSIS: Two authors independently evaluated the quality of the relevant studies and extracted the data from the included studies. MAIN RESULTS: Fifteen trials, reporting 1437 patients, 120 of whom developed transient neurologic symptoms, were included in the analysis. The use of lidocaine for spinal anaesthesia increased the risk of developing TNS. There was no evidence that this painful condition was associated with any neurologic pathology; the symptoms disappeared spontaneously by the fifth postoperative day. The relative risk (RR) for developing TNS after spinal anaesthesia with lidocaine as compared to other local anaesthetics (bupivacaine, prilocaine, procaine, levobupivacaine and ropivacaine) was 7.16 (95% confidence interval (CI) 4.02, 12.75). AUTHORS' CONCLUSIONS: The risk of developing TNS after spinal anaesthesia with lidocaine was significantly higher than when bupivacaine, prilocaine and procaine were used. The term "TNS", which implies a positive neurologic finding, should not be used for this painful condition. One study about the impact of TNS on patient satisfaction and functional impairment demonstrated that non-TNS patients were more satisfied and had less functional impairment after surgery than TNS patients, but this did not influence their willingness to recommend spinal anaesthesia.


Assuntos
Raquianestesia/efeitos adversos , Anestésicos Locais/efeitos adversos , Perna (Membro)/inervação , Lidocaína/efeitos adversos , Dor/induzido quimicamente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Anaesthesia ; 58(7): 703-6, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12886913

RESUMO

Patients in a teaching hospital in Scotland were given the opportunity to ask for further information relating to their peri-operative anaesthetic management. One investigator visited all of the patients pre-operatively and asked a standard list of anaesthetic-related questions. Our objectives were to determine what additional information patients would request before giving their consent to anaesthesia. The majority of patients (n=469, 67%) had no further questions at a point when so-called consent could have been obtained. Of the questions asked, 209 (66%) were related to anaesthesia and 93 (30%) to the proposed surgery. Only two patients in the group studied requested a full explanation of their peri-operative anaesthetic management. The question most commonly asked related to the duration of surgery, with less priority being given to questions relating to complications of anaesthesia.


Assuntos
Anestesia , Atitude Frente a Saúde , Consentimento Livre e Esclarecido , Educação de Pacientes como Assunto , Anestesia/efeitos adversos , Comunicação , Hospitais de Ensino , Humanos , Cuidados Pré-Operatórios , Estudos Prospectivos , Escócia
13.
Appl Environ Microbiol ; 67(9): 3785-94, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11525968

RESUMO

Solar evaporation ponds are commonly used to reduce the volume of seleniferous agricultural drainage water in the San Joaquin Valley, Calif. These hypersaline ponds pose an environmental health hazard because they are heavily contaminated with selenium (Se), mainly in the form of selenate. Se in the ponds may be removed by microbial Se volatilization, a bioremediation process whereby toxic, bioavailable selenate is converted to relatively nontoxic dimethylselenide gas. In order to identify microbes that may be used for Se bioremediation, a 16S ribosomal DNA phylogenetic analysis of an aerobic hypersaline pond in the San Joaquin Valley showed that a previously unaffiliated group of uncultured bacteria (belonging to the order Cytophagales) was dominant, followed by a group of cultured gamma-Proteobacteria which was closely related to Halomonas species. Se K-edge X-ray absorption spectroscopy of selenate-treated bacterial isolates showed that they accumulated a mixture of predominantly selenate and a selenomethionine-like species, consistent with the idea that selenate was assimilated via the S assimilation pathway. One of these bacterial isolates (Halomonas-like strain MPD-51) was the best candidate for the bioremediation of hypersaline evaporation ponds contaminated with high Se concentrations because it tolerated 2 M selenate and 32.5% NaCl, grew rapidly in media containing selenate, and accumulated and volatilized Se at high rates (1.65 microg of Se g of protein(-1) x h(-1)), compared to other cultured bacterial isolates.


Assuntos
Bacteroidetes/classificação , Gammaproteobacteria/classificação , Selênio/metabolismo , Cloreto de Sódio , Microbiologia da Água , Poluentes Químicos da Água/metabolismo , Agricultura , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Bacteroidetes/fisiologia , Biodegradação Ambiental , DNA Ribossômico/análise , Gammaproteobacteria/genética , Gammaproteobacteria/isolamento & purificação , Gammaproteobacteria/fisiologia , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 16S
14.
J Cataract Refract Surg ; 26(6): 810-6, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10889424

RESUMO

PURPOSE: To determine the relationship between various intraocular lens (IOL) types and the incidence of unwanted light images. SETTING: The Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. METHODS: A telephone questionnaire was administered to 302 postoperative patients who had received 1 of 6 commonly used IOLs between January and September 1998. Patients were included only if they had uneventful cataract surgery, no additional ocular pathology, and a postoperative best corrected visual acuity of 20/25 or better. A control group of 50 patients with the diagnosis of presbyopia only also participated in the questionnaire. Patients reported on incidence of glare, light sensitivity, and unwanted images. The data were analyzed for statistically significant relationships between incidence of photopsias and IOL type. RESULTS: The AcrySof 5.5 mm, AcrySof 6.0 mm, and SI-40 groups reported significantly more unwanted images than the control group (P =.0014). The 2 AcrySof groups also reported a greater incidence of light to the side causing a central flash, and the SI-40 group, a higher incidence of glare. The control group was more likely to experience symptoms of glare than any pseudophakic group. Overall, a mean of 49% of patients reported some light-related phenomenon postoperatively. The majority in all groups reported being satisfied with their eyesight despite the light-related problems. CONCLUSIONS: A significant number of pseudophakic patients reported symptoms of dysphotopsia. Patients who received an acrylic IOL with flattened edges were at increased risk of experiencing images associated with edge reflections. The SI-40 lens group, although less than the AcrySof groups, reported a higher incidence of glare than the non-AcrySof groups; however, it also had the highest number of patients still driving at night. The phakic population commonly experienced glare reported as more severe than several of the IOL groups.


Assuntos
Cristalino , Lentes Intraoculares/classificação , Pseudofacia/complicações , Transtornos da Visão/etiologia , Idoso , Extração de Catarata , Humanos , Incidência , Implante de Lente Intraocular , Luz , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários , Transtornos da Visão/fisiopatologia , Acuidade Visual
15.
Anesth Analg ; 90(5): 1162-6, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10781472

RESUMO

This study compares intrathecal (IT) fentanyl with IV ondansetron for preventing intraoperative nausea and vomiting during cesarean deliveries performed with spinal anesthesia. Thirty healthy parturients presenting for elective cesarean delivery with standardized bupivacaine spinal anesthesia were randomized to receive 20 microg IT fentanyl (Group F) or 4 mg IV ondansetron (Group O) by using double-blinded methodology. At eight specific intervals during the surgery, a blinded observer questioned the patient about nausea (1 = nausea, 0 = no nausea), observed for the presence of retching or vomiting (1 = vomiting or retching, 0 = no vomiting or retching), and recorded a verbal pain score (0-10, 0 = no pain, 10 = worst pain imaginable). Cumulative nausea, vomiting, and pain scores were calculated as the sum of the eight measurements. Intraoperative nausea was decreased in the IT fentanyl group compared with the IV ondansetron group: the median (interquartile range) difference in nausea scores was 1 (1, 2), P = 0.03. The incidence of vomiting and treatment for vomiting was not different (P = 0.7). The IT fentanyl group had a lower cumulative perioperative pain score than the IV ondansetron group; the median difference in the cumulative pain score was 12 (8, 16) (P = 0.0007). The IT fentanyl group required less supplementary intraoperative analgesia. The median difference in the cumulative fentanyl dose was 100 (75, 100) microg fentanyl, (P = 0.0002).


Assuntos
Adjuvantes Anestésicos/administração & dosagem , Analgésicos Opioides/administração & dosagem , Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Antieméticos/administração & dosagem , Cesárea , Fentanila/administração & dosagem , Ondansetron/administração & dosagem , Náusea e Vômito Pós-Operatórios/prevenção & controle , Adulto , Método Duplo-Cego , Feminino , Humanos , Injeções Intravenosas , Injeções Espinhais , Náusea e Vômito Pós-Operatórios/etiologia , Gravidez
16.
Anesthesiology ; 92(3): 665-73, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10719944

RESUMO

BACKGROUND: Oral transmucosal fentanyl citrate (OTFC) is a solid form of fentanyl that delivers the drug through the oral mucosa. The clinical utility of multiple doses of OTFC in the treatment of "breakthrough" cancer pain is under evaluation. The aim of this study was to test the hypothesis that the pharmacokinetics of OTFC do not change with multiple dosing. METHODS: Twelve healthy adult volunteers received intravenous fentanyl (15 microg/kg) or OTFC (three consecutive doses of 800 microg) on separate study sessions. Arterial blood samples were collected for determination of fentanyl plasma concentration by radioimmunoassay. The descriptive pharmacokinetic parameters (maximum concentration, minimum concentration, and time to maximum concentration) were identified from the raw data and subjected to a nonparametric analysis of variance. Population pharmacokinetic models for all subjects and separate models for each subject were developed to estimate the pharmacokinetic parameters of fentanyl after multiple OTFC doses. RESULTS: The shapes of the profiles of plasma concentration versus time for each dose of OTFC were grossly similar. No change was noted for maximum concentration or time to maximum concentration over the three doses, while minimum concentration did show a significantly increasing trend. Terminal half-lives for intravenous fentanyl and OTFC were similar. A two-compartment population pharmacokinetic model adequately represented the central tendency of the data from all subjects. Individual subject data were best described by either two- or three-compartment pharmacokinetic models. These models demonstrated rapid and substantial absorption of OTFC that did not change systematically with time and multiple dosing. CONCLUSIONS: The pharmacokinetics of OTFC were similar among subjects and did not change with multiple dosing. Multiple OTFC dosing regimens within the dosage schedule examined in this study can thus be formulated without concern about nonlinear accumulation.


Assuntos
Analgésicos Opioides/farmacocinética , Fentanila/farmacocinética , Administração Oral , Adolescente , Adulto , Analgésicos Opioides/administração & dosagem , Feminino , Fentanila/administração & dosagem , Meia-Vida , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Mucosa Bucal/metabolismo , Dinâmica não Linear , População , Radioimunoensaio
17.
Transfusion ; 38(11-12): 1046-50, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9838936

RESUMO

BACKGROUND: The yield of CD34-positive cells obtained from an apheresis procedure is determined, in part, by the efficiency of collection. Optimization of the efficiency of CD34-positive peripheral blood cell collection requires identification of predictive factors. STUDY DESIGN AND METHODS: Demographic, stem cell collection, mobilization, and disease-related measures from autologous and allogeneic donors undergoing 252 progenitor cell apheresis procedures were retrospectively reviewed. Statistical relationships between CD34 collection efficiency and the various measures were determined by correlation and multiple linear regression analysis. RESULTS: CD34 collection efficiency inversely correlated with the peripheral white cell count, hematocrit, and serum albumin concentration (R2 = 0.29). White cell count was the single best predictor of CD34 efficiency (R2 = 0.19). Donor groups with cytopenias (patients vs. normal donors; increased cycles of prior chemotherapy; bone marrow involvement; chemotherapy plus growth factor mobilization) had higher collection efficiencies. Only 29 percent of the variability in the data could be attributed to white cell count, hematocrit, and albumin concentration. The majority of the remaining variability was due to unexplained differences between donors. CONCLUSION: CD34 collection efficiencies show considerable variation. Higher peripheral white cell counts, hematocrits, and/or albumin concentrations result in decreased CD34 collection efficiency, but most of the variability in the data is not accounted for by these three factors.


Assuntos
Antígenos CD34/sangue , Remoção de Componentes Sanguíneos/métodos , Coleta de Amostras Sanguíneas/métodos , Separação Celular/instrumentação , Células-Tronco Hematopoéticas/imunologia , Adolescente , Adulto , Idoso , Contagem de Células , Feminino , Células-Tronco Hematopoéticas/citologia , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Estatísticas não Paramétricas
18.
RNA ; 4(8): 937-47, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9701285

RESUMO

The RNA subunit of bacterial ribonuclease P is a catalytic RNA that cleaves precursor tRNAs to generate mature tRNA 5' ends. A self-cleaving RNase P RNA-substrate conjugate was used in modification-interference analysis to identify purine N-7 and ribose 2'-hydroxyl functional groups that are critical to catalysis. We identify six adenine N-7 groups and only one 2'-hydroxyl that, when substituted with 7-deazaadenine or 2'-deoxy analogues, respectively, reduce the RNase P catalytic rate approximately 10-fold at pH 8 and limiting concentration of magnesium. Two sites of low-level interference by phosphorothioate modification were detected in addition to the four sites of strong interference documented previously. These modification-interference results, the absolute phylogenetic conservation of these functional groups in bacterial RNase P RNA, their proximity to the substrate-phosphate in the tertiary structure of the ribozyme-substrate complex, and the importance of some of the sites for binding of catalytic magnesium all implicate these functional groups as components of the RNase P active site. Five of the 7-deazaadenine interferences are suppressed at pH 6, where the hydrolytic step is rate-limiting, or at saturating concentrations of magnesium. We propose, therefore, that these base functional groups are specifically engaged in the catalytic center of RNase P RNA, possibly by involvement in magnesium-dependent folding. One 7-deazaadenine interference and one 2'-deoxy-interference, although partially suppressed at pH 6, are not suppressed at saturating magnesium concentrations. This implicates these groups in magnesium-independent folding of the catalytic substructure of the ribozyme.


Assuntos
Endorribonucleases/metabolismo , Precursores de RNA/metabolismo , RNA Bacteriano/metabolismo , RNA Catalítico/metabolismo , RNA de Transferência/metabolismo , Sequência de Bases , Sítios de Ligação , Desoxirribonucleotídeos/química , Endorribonucleases/química , Endorribonucleases/efeitos dos fármacos , Guanosina/análogos & derivados , Guanosina/química , Concentração de Íons de Hidrogênio , Magnésio/farmacologia , Modelos Moleculares , Dados de Sequência Molecular , Ressonância Magnética Nuclear Biomolecular , Conformação de Ácido Nucleico , Purinas/química , Processamento Pós-Transcricional do RNA , RNA Bacteriano/química , RNA Bacteriano/efeitos dos fármacos , RNA Catalítico/química , RNA Catalítico/efeitos dos fármacos , Ribonuclease P , Tionucleotídeos , Tubercidina/química
20.
Ophthalmology ; 103(8): 1196-203, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8764787

RESUMO

PURPOSE: To evaluate and compare the efficacy of topical and retrobulbar anesthesia for cataract extraction with intraocular lens implantation. METHODS: One hundred thirty-eight patients prospectively were assigned to the topical (group 1; n = 69) or retrobulbar (group 2; n = 69) anesthesia groups by permuted block restricted randomization. Group 1 received topical 0.75% bupivacaine and intravenous midazolam and fentanyl for anesthesia. Group 2 received intravenous methohexital followed by retrobulbar block with an equal mixture of 2% lidocaine and 0.75% bupivacaine plus hyaluronidase (150 U). A visual pain analogue scale was used to assess the degree of pain during the administration of anesthesia, during surgery, and post-operatively. The degree to which eye movement, touch, and light caused patient discomfort was assessed. Complications and surgical conditions were recorded. RESULTS: There was no difference in the surgical conditions (P = 0.5) or pain during surgery (P = 0.35) between the two groups. There was more discomfort during administration of topical anesthesia (P < 0.0001) and postoperatively (P < 0.05) in the topical group. Chemosis, subconjunctival hemorrhage, and eyelid hemorrhage were seen almost exclusively in the retrobulbar group. One patient in group 2 had a retrobulbar hemorrhage. Although eyeball movement and squeezing of the eyelids were present more frequently in the topical group, neither was a problem to the surgeon. CONCLUSION: Topical anesthesia can be used safely for cataract extraction. The degree of patient discomfort is only marginally higher during administration of the anesthesia and postoperatively. However, surgical training and patient preparation are the keys to the safe use of topical anesthesia.


Assuntos
Anestesia/métodos , Anestésicos Locais/administração & dosagem , Extração de Catarata , Administração Tópica , Idoso , Idoso de 80 Anos ou mais , Anestésicos Intravenosos/administração & dosagem , Bloqueio Nervoso Autônomo/métodos , Bupivacaína/administração & dosagem , Combinação de Medicamentos , Movimentos Oculares , Humanos , Hialuronoglucosaminidase/administração & dosagem , Complicações Intraoperatórias , Lentes Intraoculares , Lidocaína/administração & dosagem , Pessoa de Meia-Idade , Soluções Oftálmicas , Órbita/efeitos dos fármacos , Medição da Dor , Complicações Pós-Operatórias , Estudos Prospectivos
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