RESUMO
Healthcare workers (HCWs) have increased exposure and subsequent risk of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This case-control study was conducted to investigate the contemporaneous risks associated with confirmed SARS-CoV-2 infection amongst HCWs following in-work exposure to a confirmed coronavirus disease-2019 (COVID-19) case. We assessed the influence of demographic (age, sex, nationality, high risk co-morbidities and vaccination status) and work-related factors (job role, exposure location, contact type, personal protective equipment (PPE) use) on infection risk following nosocomial SARS-CoV-2 exposure. All contact tracing records within the hospital site during waves 1-3 of the COVID-19 pandemic in Ireland were screened to identify exposure events, cases and controls. In total, 285 cases and 1526 controls were enrolled, as a result of 1811 in-work exposure events with 745 index cases. We demonstrate that male sex, Eastern European nationality, exposure location, PPE use and vaccination status all impact the likelihood of SARS-CoV-2 infection following nosocomial SARS-CoV-2 exposure. The findings draw attention to the need for continuing emphasis on PPE use and its persisting benefit in the era of COVID-19 vaccinations. We suggest that non-work-related factors may influence infection risk seen in certain ethnic groups and that infection risk in high-risk HCW roles (e.g. nursing) may be the result of repeated exposures rather than risks inherent to a single event.
Assuntos
COVID-19 , Infecção Hospitalar , Masculino , Humanos , Pandemias , COVID-19/epidemiologia , SARS-CoV-2 , Estudos de Casos e Controles , Irlanda/epidemiologia , Infecção Hospitalar/epidemiologia , Pessoal de Saúde , Fatores de Risco , HospitaisRESUMO
OBJECTIVE: To assess the overall prognosis of patients with ampullary carcinomas and evaluate the presentation, diagnosis, pathology and management of these potentially highly curable tumours, attempting to relate these factors to overall survival. PATIENTS AND METHODS: Forty patients with ampullary carcinoma were reviewed. Age, Sex, nature and duration of history, laboratory information at admission, results of diagnostic radiology, endoscopic retrograde cholangiopancreatograms and pathological findings were considered. Both curative and palliative management strategies were reviewed. RESULTS: The overall median survival was 19 months. The median duration of history was 5.9 +/- 5.4. weeks, with no significant difference in survival between patients with short and those with long histories (P = 0.46). Twenty nine (73%) patients were potentially resectable, but only 15 (37%) underwent potentially curative surgery. The difference in survival between the Whipple's (13) and the endoscopically stented (20 ) groups was not significant (p = 0.08). The Whipple's group were significantly younger than the stented group (P = 0.001) and had a significant operative morbidity, re-operation rate (38%) and post-operative mortality (15%). Only five of 13 patients were alive following Whipple's treatment after a mean follow-up of 18.9 months. Sphincterotomy before Whipple's treatment improved survival significantly (P = 0.04); absence of jaundice, exophytic macroscopic appearance, well-differentiated tumours and early stage were also associated with good survival. Endoscopic retrograde cholangiopancreatography has a high diagnostic yield and a low associated morbidity and mortality, with endoscopic papillectomy aiding cannulation while effective palliation was provided through stenting, endoscopic papillectomy and laser debulking of obstructing tumours. Little benefit was obtained from chemoradiotherapy. CONCLUSION: Despite the potential for curative resection in patients with ampullary carcinoma, the majority of such patients are unsuitable for curative surgery on grounds of age, general health status or advanced disease; since only 37% of patients undergo potentially curative surgery the condition has a poor prognosis.
Assuntos
Ampola Hepatopancreática , Neoplasias do Ducto Colédoco/mortalidade , Idoso , Colangiopancreatografia Retrógrada Endoscópica , Neoplasias do Ducto Colédoco/patologia , Neoplasias do Ducto Colédoco/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reoperação , Fatores Sexuais , Stents , Taxa de SobrevidaRESUMO
The lens crystallins were analyzed in normal dogs and Miniature offSchnauzer dogs with congenital cataract formation. There was an increase in the relative proportions of alpha and beta L-crystallin and a decrease in the beta H and gamma-crystallin with increasing age in the noncataractous lens. These trends were advanced in the age-matched cataractous lenses. "Advanced aging" trends were also noted in various polypeptide components of beta-crystallin. Specifically, the appearance of a 29K band as well as a reversal of the 26K to 27.6K ratio occurred at an earlier age in the cataractous lens than in the clear lens. Three subunits of approximately 19K, 20K, and 21.5K were present on SDS-PAGE for alpha-crystallin from the cataractous lens as opposed to only two of 19K and 21.5K from the clear lens. However, if the protein was not heated following resolubilization in buffer containing 2% SDS and 5% 2-mercaptoethanol, only two subunits of 20K and 21.5K were evident in both clear and cataractous lenses. The electrophoretic behavior observed for both alpha and gamma-crystallins did not appear to be age related.
Assuntos
Catarata/metabolismo , Cristalinas/isolamento & purificação , Cristalino/metabolismo , Fatores Etários , Animais , Catarata/genética , Cães , Eletroforese em Gel de Poliacrilamida , Focalização Isoelétrica , Peso MolecularRESUMO
Adult female dogs or pony mares were subjected to a nonlethal dose of CCl4 (0.5 ml/kg of body weight). Amounts of several plasma enzymes thought to be indicative of hepatic disease were monitored. Plasma enzymes alanine aminotransferase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), arginase, gamma-glutamyltransferase (GGT), and iditol dehydrogenase (ID), as well as total plasma bilirubin, were determined in these animals before and after the administration of the CCl4. In the dog, GGT was not significantly increased, whereas ALP values were increased during days 1 to 6. In the pony, GGT was significantly increased during the entire course of the study, whereas ALP exhibited only small, transient (though significant) increases. Responses of ID, AST, and ALP were unremarkable when compared between the pony and the dog. Total bilirubin was significantly (P less than or equal to 0.05) increased from days 1 to 4 (pony) or days 5 to 8 (dog) after the CCl4 dose, but subsequently returned to or decreased below base-line values. Animals did not have evidence of icterus at any time. Seemingly, the dog and the pony are distinct clinical entities, and only the appropriate laboratory tests for each species should be used to provide information for the clinicopathologic evaluation of hepatic disease.
Assuntos
Tetracloreto de Carbono/farmacologia , Cães/metabolismo , Cavalos/metabolismo , Fígado/efeitos dos fármacos , Fosfatase Alcalina/sangue , Animais , Arginase/sangue , Bilirrubina/sangue , Doenças do Cão/enzimologia , Feminino , Doenças dos Cavalos/enzimologia , L-Iditol 2-Desidrogenase/sangue , Fígado/enzimologia , Hepatopatias/enzimologia , Hepatopatias/veterinária , Transferases/sangueRESUMO
Biliary excretion of bilirubin, including the conjugate composition, was studied during feeding and during a 2.5-day fast of three pony mares with chronic external biliary (T-tube) fistulas. Fasting bilirubin excretion (1.96 +/- 0.74 microgram/min/kg of body weight), after establishing a new steady state, was not different from excretion during feeding (1.99 +/- 0.45 microgram/min/kg). Hyperbilirubinemia of fasting resulted from a reduced removal of plasma bilirubin rather than from an increased input of bilirubin into the plasma. Relative plasma excretion of the individual conjugate fractions of biliary bilirubin was not changed by fasting.
Assuntos
Bile/metabolismo , Bilirrubina/metabolismo , Jejum/veterinária , Cavalos/metabolismo , Animais , Bilirrubina/sangue , Glicemia/análise , Ácidos Graxos não Esterificados/sangue , FemininoRESUMO
Amounts of reduced, oxidized, and protein-bound glutathione (GSH) were measured in normal and cataractous lenses of pups and adult dogs. Lenses from pups included normal lenses from clinically normal pups, clear lenses from Beagle pups bred for glaucoma, and congenital cataractous lenses from Miniature Schnauzer pups. Lenses from adults included normal lenses from normal mixed-breed dogs, congenital cataractous lenses from Miniature Schnauzers, and complete mature cataractous lenses from clinical patients of different breeds. Glutathione in the normal lenses from pups and adult dogs is predominantly reduced GSH; oxidized GSH is about 2.1% to 2.6% of the reduced GSH values. The reduced GSH values are lower in normal pups [7.08 mumoles/g (wet wt) of lens] than in adults [7.83 mumoles/g (wet wt) of lens]; reduced GSH values decrease further in cataract formation. The decrease in oxidized GSH values parallel those of reduced GSH, except in the advanced cataracts of clinical patients in which oxidized GSH [0.045 mumoles/g (wet wt) of lens] was 9% of the GSH values. The GSH bound to soluble and insoluble lens proteins of congenital cataractous Miniature Schnauzer pups was significantly (P less than 0.01 and P less than 0.02, respectively) lower per gram of protein than that in pups with normal lenses. However, the soluble and insoluble protein-bound GSH of congenital cataractous lenses of adult Miniature Schnauzers and lenses in clinical patients with mature cataracts [based on mumole of GSH/g (wet wt) of lens] were not significantly different (P greater than 0.05) from that in adult dogs with normal lenses.
Assuntos
Catarata/veterinária , Doenças do Cão/metabolismo , Cães/metabolismo , Glaucoma/veterinária , Glutationa/análise , Cristalino/análise , Envelhecimento , Animais , Catarata/congênito , Catarata/metabolismo , Glaucoma/metabolismo , Glutationa/metabolismo , HumanosRESUMO
STUDY OBJECTIVES: To compare the effects on oxygen saturation as measured by pulse oximetry (SpO2) and ECG changes of endoscopy alone, sedation followed by endoscopy, and sedation followed by endoscopy with supplemental oxygen (O2) during upper gastrointestinal (GI) endoscopy. STUDY DESIGN: Randomized trial. SETTING: Outpatient gastroenterology clinic at a university medical center. PATIENTS: 58 healthy patients scheduled for outpatient upper GI endoscopy, with no clinical evidence of respiratory disease. INTERVENTIONS: Patients were randomly allocated to three groups: Group 1 received no benzodiazepines before endoscopy and breathed room air throughout (n = 18), Group 2 received midazolam intravenously (i.v.) before endoscopy and breathed room air throughout (n = 20), and Group 3 received i.v. midazolam and 2 L/min O2 through nasal cannulae during endoscopy (Group 3; n = 20). MEASUREMENTS AND MAIN RESULTS: Data collection, which included heart rate, cardiac rhythm, and SpO2 were recorded at seven intervals: baseline, topical anesthesia of the oropharynx, mouth gag insertion, endoscope insertion, biopsy, endoscope removal, and five minutes postendoscopy. In Group 2, mean SpO2 decreased after midazolam was administered and remained depressed during endoscopy (p < 0.05). After midazolam was given, Group 2 patients differed significantly from patients in Groups 1 and 3 (p < 0.05). CONCLUSIONS: The use of hypnotic doses of benzodiazepines is the primary factor responsible for the reduced oxygenation seen during endoscopy. Neither the presence of the endoscope alone nor the use of midazolam with supplemental O2 caused a decreased oxygenation. This study also suggests that the routine use of benzodiazepines is unnecessary when the endoscopy is of short duration, and the endoscopist employs good topicalization of the oropharynx. In patients who require sedation for endoscopy, O2 administration prevents hypoxemia.
Assuntos
Endoscopia Gastrointestinal , Hipóxia/prevenção & controle , Midazolam/efeitos adversos , Oxigenoterapia , Eletrocardiografia/efeitos dos fármacos , Feminino , Humanos , Hipóxia/induzido quimicamente , Injeções Intravenosas , Masculino , Midazolam/administração & dosagem , Pessoa de Meia-Idade , Oximetria , Pré-MedicaçãoRESUMO
BACKGROUND: Most large published series on endoscopic retrograde cholangiopancreatography (ERCP) are multicentre-based and consequently reflect varying experience. AIMS: To assess morbidity and mortality rates of ERCP in a single tertiary referral centre. METHODS: A series of 1,758 consecutive ERCPs performed in 1,148 patients between 1991 and 1994 were reviewed to evaluate indications, findings, procedures, success, complication and mortality rates. RESULTS: There were 1,108 (63%) successful initial ERCPs, 11% failed cannulation attempts and 26% follow-up ERCPs. The desired duct was successfully cannulated in 96.5% of cases. Initial cannulation failure rate was 8.8%. Twenty-seven per cent had normal ERCPs, 30% had choledocholithiasis and 22% had strictures. Fifty-five per cent had therapeutic ERCPs. Major complications occurred in 3.5% with four ERCP-related deaths (0.35%). Therapeutic ERCP had a higher incidence of major complications compared to diagnostic ERCP: 4.6% vs 2.1%, (p=0.02); and mortality rate was 0.5% vs 0.2%, (p=0.4). Significant haemorrhage secondary to biliary sphincterotomy, pre-cut papillotomy and snare papillectomy accounted for most of the difference (1.6%). CONCLUSIONS: The majority of ERCPs were performed in elderly patients, over half of whom required therapeutic ERCP. Therapeutic ERCP carried significantly higher complication rate compared with diagnostic ERCP. Unsuccessful cannulation and follow-up ERCP accounted for 11% and 26% of ERCP workload, respectively.
Assuntos
Doenças dos Ductos Biliares/diagnóstico por imagem , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças dos Ductos Biliares/terapia , Colangiopancreatografia Retrógrada Endoscópica/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosAssuntos
Arginase/sangue , Colestase Extra-Hepática/veterinária , Doenças do Cão/diagnóstico , Hepatopatias/veterinária , gama-Glutamiltransferase/sangue , Animais , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas , Colestase Extra-Hepática/sangue , Colestase Extra-Hepática/diagnóstico , Colestase Extra-Hepática/etiologia , Doenças do Cão/induzido quimicamente , Doenças do Cão/enzimologia , Cães , Feminino , Ligadura , Hepatopatias/sangue , Hepatopatias/diagnósticoRESUMO
Gene therapy is an innovative technique utilized in the treatment of a primary immunodeficiency known as severe combined immune deficiency syndrome (SCIDS). The first human trials of gene therapy for SCIDS were conducted in 1990, by attempting to insert the gene for adenosine deaminase into peripheral white blood cells to treat children with adenosine deaminase (ADA)-deficiency SCIDS. Recently, three infants with ADA-deficiency SCIDS received gene therapy with genetically manipulated hematopoietic stem cells. This clinical update reviews basic immunology function and malfunction, describes gene therapy, and specifically highlights hematopoietic stem cell gene therapy treatment for ADA-deficiency SCIDS.
Assuntos
Terapia Genética/métodos , Células-Tronco Hematopoéticas , Imunodeficiência Combinada Severa/terapia , Assistência ao Convalescente , Humanos , Lactente , Recém-Nascido , Enfermagem Neonatal , Alta do Paciente , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/imunologiaRESUMO
The synthetic protease inhibitor N-tosyl-L-lysine-chloromethyl ketone (TLCK) acts to inhibit transcription when added to cell lines growing in vitro. This inhibition of transcription is most pronounced in transformed cells where TLCK is very toxic at concentrations as low as 25 mug/ml of culture medium. Non-transformed cells are more resistant to the effect of TLCK, requiring ten times more TLCK to produce a comparable inhibition of transcription. The effect of this protease inhibitor on transcription can be prevented by preincubation of the cells in reduced glutathione or cysteine; however, the cells can not be rescued from the effect of TLCK even if glutathione or cysteine are added to the culture medium within five minutes of the addition of TLCK.
Assuntos
Clorometilcetonas de Aminoácidos/farmacologia , Divisão Celular/efeitos dos fármacos , Transformação Celular Neoplásica , Tosilina Clorometil Cetona/farmacologia , Transcrição Gênica/efeitos dos fármacos , Animais , Linhagem Celular , Células Cultivadas/metabolismo , Meios de Cultura , Cisteína/metabolismo , Depressão Química , Glutationa/metabolismo , Camundongos , RNA/biossíntese , RNA Neoplásico/biossínteseRESUMO
An unconjugated hyperbilirubinemia has been observed in all species of normal indigo snakes. The plasma clearance of large organic anions such as sulfobromophthalein and unconjugated bilirubin was markedly delayed when compared to other snake species. Endogenous bile flow and biliverdin and bilirubin excretory rates and the excretion of bile pigments after a bilirubin load were measured in various snakes. The indigo snake represents a new animal model in which to study mechanisms important to hepatic anion uptake and biliary transport.
Assuntos
Hiperbilirrubinemia/fisiopatologia , Serpentes/fisiologia , Animais , Bile/fisiologia , Bile/fisiopatologia , Bilirrubina/sangue , Modelos Animais de Doenças , Humanos , Especificidade da EspécieRESUMO
We have developed a technique for isolating nuclei and nuclear envelope(s) (NE) from Chinese hamster ovary (CHO) cells which does not depend on the use of detergents to solubilize contaminating cytoplasm. In our procedure NE are prepared from purified nuclei by nuclease digestion and subsequent high salt-sucrose gradient centrifugation. The nuclei and NE fractions are free of significant contamination by other subcellular organelles as judged by electron microscopy and enzyme analysis. Examination of the peptide and glycopeptide composition of the NE fraction by sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveals a very complex coomassie blue staining profile with prominent bands in the 55 000-75 000 molecular weight range. Using this NE isolation technique, we have examined the breakdown and re-formation of the NE during a limited stage (late G2, M, and early G1) of the replicative cycle in synchronized populations of CHO cells. Our data demonstrate that a minimum of 60% of the early G1 NE protein and a minimum of 50% of the early G1 NE phospholipid were present in the cell during the preceding G2 phase of the cell cycle and were reutilized in the re-formation of the NE occurring during late M and early G1. Our evidence suggests that the vast majority of the newly synthesized peptides and glycopeptides of the NE which appear in the daughter NE are synthesized during the early G1 phase of the replicative cycle. Examination of the NE peptides by one-dimensional gel electrophoresis suggests that no reproducible changes in NE peptide composition can be correlated with specific phases of the cell cycle.
Assuntos
Mitose , Membrana Nuclear/fisiologia , Animais , Ciclo Celular , Fracionamento Celular/métodos , Linhagem Celular , Cricetinae , Cricetulus , Feminino , Cinética , Leucina/metabolismo , Lipídeos de Membrana/biossíntese , Membrana Nuclear/metabolismo , Membrana Nuclear/ultraestrutura , Nucleoproteínas/biossíntese , Ovário , Ácidos Fosfatídicos/metabolismo , Fosfolipídeos/biossínteseRESUMO
BACKGROUND: Selective cannulation of the biliary and pancreatic ducts is considered to be the most difficult and rate limiting aspect of diagnostic endoscopic retrograde cholangiopancreatography (ERCP). AIMS/METHODS: A novel technique for difficult cannulation is described and its potential role in relieving malignant duodenal obstruction secondary to ampullary carcinoma. A diagnostic endoscopic papillectomy was performed in 10 patients in whom previous attempts at cannulation had failed. Five patients had exophytic ampullary carcinomas, one had carcinoma of the head of pancreas, two had an oedematous ampulla secondary to low common bile duct stones, while two had protuberant ampullae with ectopic orifices. The technique entails snaring the ampulla flush with the duodenal wall using a polypectomy snare and in a similar fashion to polypectomy removing the ensnared ampulla with diathermy using a coagulation current. The underlying exposed ducts can then be cannulated while the ensnared ampulla can be retrieved to aid histological diagnosis. RESULTS: Successful cannulation was achieved in all 10 cases with significant haemorrhage in one patient (10%). Four of the snared ampullary carcinomas (80%) were retrieved enabling a histological diagnosis to be made. CONCLUSIONS: This study demonstrates the potential role for endoscopic papillectomy as a means of cannulation in difficult circumstances, however larger comparative studies are required.
Assuntos
Ampola Hepatopancreática/cirurgia , Cateterismo/métodos , Colangiopancreatografia Retrógrada Endoscópica , Doenças do Ducto Colédoco/cirurgia , Endoscopia do Sistema Digestório/métodos , Idoso , Colangiopancreatografia Retrógrada Endoscópica/métodos , Neoplasias do Ducto Colédoco/cirurgia , Diatermia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , ReoperaçãoRESUMO
BACKGROUND: Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma. We conducted a prospective, randomized trial comparing surgery alone with combined chemotherapy, radiotherapy, and surgery. METHODS: Patients assigned to multimodal therapy received two courses of chemotherapy in weeks 1 and 6 (fluorouracil, 15 mg per kilogram of body weight daily for five days, and cisplatin, 75 mg per square meter of body-surface area on day 7) and a course of radiotherapy (40 Gy, administered in 15 fractions over a three-week period, beginning concurrently with the first course of chemotherapy), followed by surgery. The patients assigned to surgery had no preoperative therapy. RESULTS: Of the 58 patients assigned to multimodal therapy and the 55 assigned to surgery, 10 and 1, respectively, were withdrawn for protocol violations. At the time of surgery, 23 of 55 patients (42 percent) treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases, as compared with 45 of the 55 patients (82 percent) who underwent surgery alone (P<0.001). Thirteen of the 52 patients (25 percent) who underwent surgery after multimodal therapy had complete responses as determined pathologically. The median survival of patients assigned to multimodal therapy was 16 months, as compared with 11 months for those assigned to surgery alone (P=0.01). At one, two, and three years, 52, 37, and 32 percent, respectively, of patients assigned to multimodal therapy were alive, as compared with 44, 26, and 6 percent of those assigned to surgery, with the survival advantage favoring multimodal therapy reaching significance at three years (P=0.01). CONCLUSIONS: Multimodal treatment is superior to surgery alone for patients with resectable adenocarcinoma of the esophagus.
Assuntos
Adenocarcinoma/cirurgia , Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/terapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Adulto , Idoso , Cisplatino/uso terapêutico , Terapia Combinada , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Feminino , Fluoruracila/uso terapêutico , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
We have demonstrated that an established hamster cell line (NIL 8 M-2) will adhere to the bioceramic bioglass. The rate at which the NIL 8 M-2 cells assume a spread morphology on bioglass is density dependent and the morphology displayed by NIL 8 M-2 cells attached to bioglass is much more elongated than that displayed by NIL 8 M-2 cells attached to nonreactive glass. Precoating the bioglass with the plasma form of human fibronectin significantly reduces the density dependent nature of cell spreading. Coating the bioglass with fibronectin also reduces the time required for cell spreading and changes the morphology of the attached cells from an elongated to an extremely flattened shape. Our work raises the possibility that bone-implant adhesion might be improved by introducing molecules relevant to cell-substrate attachment into the biomaterial prior to implantation.
Assuntos
Materiais Biocompatíveis , Adesão Celular/efeitos dos fármacos , Fibronectinas/farmacologia , Animais , Cimentos Ósseos , Linhagem Celular , Cerâmica , Cricetinae , Próteses e ImplantesRESUMO
Medical treatment of cholesterol gall stones aims to dissolve the stones leaving the biliary tract stone-free and the gall bladder in situ. The introduction of extracorporeal shock wave lithotripsy and contact solvent therapy with methyl tert butyl ether have revolutionised the medical management of both gall bladder stones and bile duct stones which are too large to be treated by sphincterotomy. Both approaches represent a major advance over cheno- and ursodeoxycholic acid which are effective in less than 30% of cases and require prolonged therapy. All medical treatments require a functioning gall bladder and suffer from relapse rates in the order of 10% per annum. Secondary prophylaxis is expensive and the rate of compliance and long term safety have yet to be established.
Assuntos
Colelitíase/terapia , Ácidos e Sais Biliares/uso terapêutico , Colelitíase/química , Colesterol , Humanos , LitotripsiaRESUMO
BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) has a significant mortality, morbidity, and failed cannulation rate. Magnetic resonance cholangiopancreatography (MRCP) is a safer, noninvasive method of imaging the pancreaticobiliary tree. A substantial number of patients are referred for ERCP because of abdominal pain, a high proportion of whom have normal ducts or pathology not requiring interventional ERCP. The aim was to assess the potential impact of MRCP on overall ERCP workload and patient outcome if MRCP were the primary investigation in patients referred for ERCP because of abdominal pain. PATIENTS AND METHODS: 1758 consecutive ERCPs performed in 1148 patients over a 3-year period in a single tertiary referral center in the pre-MRCP era were reviewed. Cannulation failure, ERCP findings, need for follow-up ERCP and all 30-day major complication rates were analyzed with regard to clinical indications. RESULTS: The overall workload comprised 1108 (63 %) successful initial ERCPs, 188 (11 %) failed cannulation attempts and 462 (26 %) follow-up ERCPs. Of the patients, 299 (27 %) had normal ERCP findings, 331 (30 %) had choledocholithiasis and 246 (22 %) had strictures. lf MRCP had been used as the primary imaging investigation in the 451 patients (39 %) referred for ERCP because of abdominal pain, we estimate that 197 patients (44 %) would have avoided ERCP, and the overall ERCP workload would have been reduced by 13 %. Initial MRCP in suspected gallstone pancreatitis and certain miscellaneous groups, it was estimated, would have further decreased ERCP workload by 9 %. Four of 40 major ERCP-related complications (3.5 %) and one of four ERCP-related deaths (0.35 %) would potentially have been avoided. CONCLUSIONS: Initial MRCP in patients referred with abdominal pain would potentially have avoided ERCP in 44 % of cases, reduced ERCP workload by 13 % and significantly reduced patient morbidity and mortality. The relatively small reduction in ERCP workload among these patients reflects the fact that over half of them had probable sphincter dysfunction, a significant proportion of whom might have benefited from biliary manometry and/or endoscopic intervention despite a normal MRCP. Furthermore, a small number of patients with calculi and subtle biliary and pancreatic strictures would be missed by this approach.
Assuntos
Dor Abdominal/etiologia , Colangiopancreatografia Retrógrada Endoscópica , Doenças do Sistema Digestório/diagnóstico , Imageamento por Ressonância Magnética , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colangiopancreatografia Retrógrada Endoscópica/estatística & dados numéricos , Protocolos Clínicos , Meios de Contraste , Doenças do Sistema Digestório/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Carga de Trabalho/economia , Carga de Trabalho/estatística & dados numéricosRESUMO
BACKGROUND: The cysteinyl leukotrienes are important mediators of bronchial asthma. The clinical effect of montelukast, a potent cysteinyl leukotriene-receptor antagonist, was investigated in a randomized, placebo-controlled, multicenter, parallel-group, dose-ranging study. METHODS: After a 3-week, single-blind, placebo run-in period, 343 asthmatic patients (FEV1 40% to 80% of the predicted value with an improvement in FEV1 of at least 15% [absolute value] after receiving inhaled beta-agonists on at least two occasions) were randomly assigned to one of six treatment groups: placebo; 10, 100, or 200 mg once daily montelukast in the evening; or 10 or 50 mg twice daily montelukast for a 6-week, double-blind treatment period followed by a 1-week placebo washout period. All patients used inhaled, short-acting beta-agonists as needed. RESULTS: All montelukast doses caused similar and significant differences compared with placebo in asthma control endpoints. The least-square mean difference between pooled montelukast groups and placebo in the percentage change from baseline in morning FEV1 (10.30%; 95% CI: 5.56 to 15.04), as-needed beta-agonist use (-0.98 puffs; 95% CI: -1.53 to -0.44), morning peak expiratory flow rate (18.80 L/min; 95% CI: 8.62 to 28.98), physicians' and patients' global evaluations, and asthma-specific quality-of-life scores were all significant (p < or = 0.050). The incidence of adverse experiences was not dose related and was similar between placebo and montelukast treatment. CONCLUSION: Montelukast caused a significant improvement in chronic asthma at an oral, once daily evening dose as low as 10 mg.
Assuntos
Acetatos/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Antagonistas de Leucotrienos , Quinolinas/uso terapêutico , Acetatos/efeitos adversos , Adolescente , Adulto , Idoso , Antiasmáticos/efeitos adversos , Asma/fisiopatologia , Qualidade de Produtos para o Consumidor , Ciclopropanos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quinolinas/efeitos adversos , Método Simples-Cego , Sulfetos , Resultado do TratamentoRESUMO
PURPOSE: The safety, tolerability, and pharmacokinetics of intravenous *i.v.) montelukast sodium (Singulair, MK-0476), and the oral bioavailability of montelukast sodium in healthy males and healthy females were studied. METHODS: This was a two-part study. Part I was a four-period study in males of rising i.v. doses of montelukast sodium (3, 9, and 18 mg) administered as 15-minute constant-rate i.v. infusions (Periods 1-3), followed by a 10-mg oral tablet dose of montelukast sodium (Period 4) under fasting conditions. Part II was a four-period study in females of i.v. montelukast sodium (9 mg) infused over 15 and 5 minutes (Periods 5 and 6, respectively) or injected as a bolus over 2 minutes (Period 7), followed by a 10-mg oral tablet dose of montelukast sodium (Period 8). Plasma samples were collected and analyzed by HPLC. RESULTS: In males (N = 6), as the i.v. dose of montelukast sodium increased from 3 to 18 mg, the area under the plasma concentration-time curve of montelukast sodium from time 0 to infinity (AUC) increased proportionately. The mean values of plasma clearance (CL), steady-state volume of distribution (Vss), plasma terminal half-life (t1/12), and mean residence time in the body (MRTi.v.) of montelukast sodium were 45.5 ml/min, 10.5 1, 5.1 hr, and 3.9 hr, respectively, and remained essentially constant over the i.v. dosage range. Following oral administration of a 10-mg tablet of montelukast sodium, the AUC, maximum plasma concentration (Cmax), time when Cmax occurred (Tmax), apparent t1/12, mean absorption time (MAT), and bioavailability (F) of montelukast sodium averaged 2441 ng.hr/ml, 385 ng/ml. 3.7 hr, 4.9 hr, 3.4 hr, and 66%, respectively. Following i.v. administration of 9 mg of montelukast sodium to females (N = 6), the values of CL, Vss, t1/2, and MRT i.v. averaged 47.6 ml/min, 9.6 1, 4.5 hr, and 3.6 hr, respectively. Following oral administration of a 10-mg tablet to females, the mean AUC, Cmax, Tmax, apparent t1/2, MAT and F were 2270 ng.hr/ml, 350 ng/ml, 3.3 hr, 4.4 hr, 2.6 hr, and 58%, respectively. These parameter values were similar to or slightly smaller than those in healthy males receiving the same i.v. and oral doses. CONCLUSIONS: The disposition kinetics of montelukast sodium were linear. Gender had little or no effect on the kinetics of montelukast sodium. Safety results from this study indicate that intravenous doses of montelukast sodium from 3 to 18 mg and a 10-mg oral dose are well tolerated.