RESUMEN
Unlike conventional chemical drugs where immunogenicity typically does not occur, the development of anti-drug antibodies following treatment with biologics has led to concerns about their impact on clinical safety and efficacy. Hence the elucidation of the immunogenicity of biologics is required for drug approval by health regulatory authorities worldwide. Published ADA 'incidence' rates can vary greatly between same-class products and different patient populations. Such differences are due to disparate bioanalytical methods and interpretation approaches, as well as a plethora of product-specific and patient-specific factors that are not fully understood. Therefore, the incidence of ADA and their association with clinical consequences cannot be generalized across products. In this context, the intent of this review article is to discuss the complex nature of ADA and key nuances of the methodologies used for immunogenicity assessments, and to dispel some fallacies and myths.
Asunto(s)
Anticuerpos Neutralizantes/inmunología , Formación de Anticuerpos/inmunología , Productos Biológicos/antagonistas & inhibidores , Productos Biológicos/inmunología , Anticuerpos Neutralizantes/sangre , Productos Biológicos/uso terapéutico , Humanos , Inmunoensayo/métodosRESUMEN
BACKGROUND: Preoperative anaemia is associated with adverse postoperative outcomes. Data on raised preoperative haematocrit concentration are limited. This study aimed to evaluate the effect of raised haematocrit on 30-day postoperative mortality and vascular events in patients undergoing major surgery. METHODS: This was a cohort study using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Thirty-day mortality and vascular events, demographics and perioperative risk factors were obtained for adults undergoing major surgery. The adjusted effect of raised (over 0·50) compared with normal (0·41-0·50, American Medical Association reference range) preoperative haematocrit concentration on postoperative outcomes was assessed. Separate sex-specific analyses were also conducted, using haematocrit concentration thresholds commonly used in the diagnosis and management of apparent or absolute erythrocytosis. RESULTS: Some 3961 (2·0 per cent) of 197 469 patients had a raised haematocrit concentration before surgery. After adjustment, the 30-day postoperative mortality rate was higher in patients with raised haematocrit than in those without (odds ratio (OR) 2·23, 95 per cent confidence interval 1·77 to 2·80). Thirty-day rates of deep vein thrombosis (OR 1·95, 1·44 to 2·64) and pulmonary embolism (OR 1·79, 1·17 to 2·73), but not myocardial infarction or stroke, were also higher in patients with a raised haematocrit concentration. The effect on mortality was noted beyond the haematocrit thresholds of 0·48 in women and 0·52 in men; the effect estimates were considerably higher for values exceeding 0·54. Values between 0·41 and 0·45 were not associated with increased mortality risk. Similar observations were noted for venous thrombosis, although with apparent sex differences. CONCLUSION: A raised haematocrit concentration was associated with an increased risk of 30-day mortality and venous thrombosis following major surgery.
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Complicaciones Posoperatorias/mortalidad , Enfermedades Vasculares/mortalidad , Estudios de Cohortes , Femenino , Hematócrito/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Infarto del Miocardio/mortalidad , Policitemia/mortalidad , Complicaciones Posoperatorias/etiología , Cuidados Preoperatorios/mortalidad , Embolia Pulmonar/etiología , Embolia Pulmonar/mortalidad , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidad , Enfermedades Vasculares/etiología , Trombosis de la Vena/etiología , Trombosis de la Vena/mortalidadRESUMEN
Arteriovenous malformations are common causes of lower gastrointestinal bleeding in the elderly. Among them, angiodysplasia is one subtype that appears on endoscopy as red, flat superficial lesions, and sometimes slightly elevated. Colonic angiodysplasia is very rarely seen as a polypoid lesion. The present case describes a bleeding large polypoid colonic angiodysplasia in a 60-year-old man. It was removed endoscopically using a PolyLoop ligature device without complications.
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Angiodisplasia/cirugía , Enfermedades del Colon/cirugía , Colonoscopía , Hemorragia Gastrointestinal/etiología , Angiodisplasia/patología , Hemorragia Gastrointestinal/cirugía , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND STUDY AIMS: Colonoscopy preparation usually involves the intake of large volumes of polyethylene glycol electrolyte solution (PEG-ES) in combination with a clear-liquid diet (CLD). Liberalization of the diet might enhance the tolerance to PEG-ES without compromising the quality of the preparation. The primary aims of this study were to evaluate the efficacy and tolerability of PEG-ES given with a CLD compared with a fiber-free diet (FFD) for colonoscopy preparation. The incidence of adverse events among patients in the two diet groups was also assessed as a secondary outcome. METHODS: This was a single-center randomized, prospective, single-blind study. A total of 200 patients undergoing colonoscopy were randomized to either CLD or FFD in addition to PEG-ES. RESULTS: Patients in the FFD group were able to drink more PEG-ES (mean +/- SD, 3.9 +/- 0.3 L) compared with those in the CLD group (3.3 +/- 0.7 L) ( P < 0.01). The quality of the preparation was significantly better in the FFD group, with more patients having satisfactory preparations than those in the CLD group (81.4 % vs. 52.0 %; P < 0.001). Tolerance to the preparation was higher in the FFD group compared with the CLD group, with significantly more patients adhering to the FFD regimen ( P < 0.001). There were more adverse events experienced in the CLD group, with odds ratios of 1.9 for nausea (95 % confidence interval [CI] 1.0 - 3.6), 3.8 for vomiting (95 % CI 1.3 - 11.3), and 3.0 for headache (95 % CI 1.5 - 5.9). CONCLUSION: FFD given with PEG-ES on the day before colonoscopy is a more effective regimen than the standard CLD regimen, and is better tolerated by patients.
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Catárticos/administración & dosificación , Colonoscopía/métodos , Dieta , Fibras de la Dieta/administración & dosificación , Electrólitos/administración & dosificación , Polietilenglicoles/administración & dosificación , Cuidados Preoperatorios/métodos , Administración Oral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Cooperación del Paciente , Satisfacción del Paciente , Método Simple Ciego , Resultado del Tratamiento , Adulto JovenRESUMEN
This review examines the substantial changes that have taken place in marine habitats and resources of the Gulf over the past decade. The habitats are especially interesting because of the naturally high levels of temperature and salinity stress they experience, which is important in a changing world climate. However, the extent of all natural habitats is changing and their condition deteriorating because of the rapid development of the region and, in some cases from severe, episodic warming episodes. Major impacts come from numerous industrial, infrastructure-based, and residential and tourism development activities, which together combine, synergistically in some cases, to cause the observed deterioration in most benthic habitats. Substantial sea bottom dredging for material and its deposition in shallow water to extend land or to form a basis for huge developments, directly removes large areas of shallow, productive habitat, though in some cases the most important effect is the accompanying sedimentation or changes to water flows and conditions. The large scale of the activities compared to the relatively shallow and small size of the water body is a particularly important issue. Important from the perspective of controlling damaging effects is the limited cross-border collaboration and even intra-country collaboration among government agencies and large projects. Along with the accumulative nature of impacts that occur, even where each project receives environmental assessment or attention, each is treated more or less alone, rarely in combination. However, their combination in such a small, biologically interacting sea exacerbates the overall deterioration. Very few similar areas exist which face such a high concentration of disturbance, and the prognosis for the Gulf continuing to provide abundant natural resources is poor.
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Cambio Climático , Ecosistema , Agua de Mar , Contaminación del Agua/efectos adversos , Animales , Océano Índico , Medición de Riesgo , Agua de Mar/química , Agua de Mar/microbiología , Emiratos Árabes UnidosAsunto(s)
Coristoma/patología , Hepatopatías/patología , Páncreas , Gastropatías/patología , Dolor Abdominal/etiología , Dolor Abdominal/patología , Dolor Abdominal/cirugía , Enfermedad Aguda , Coristoma/diagnóstico por imagen , Coristoma/cirugía , Humanos , Hepatopatías/diagnóstico por imagen , Hepatopatías/cirugía , Masculino , Persona de Mediana Edad , Pancreatitis/complicaciones , Pancreatitis/patología , Pancreatitis/cirugía , Estómago/diagnóstico por imagen , Estómago/patología , Gastropatías/diagnóstico por imagen , Gastropatías/cirugía , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: Pain or its associated trauma impairs oral absorption of drugs due, perhaps, to a diminished disintegration and dissolution rate secondary to suppression of the vagal nervous system. We first examined whether ibuprofen absorption is impaired on suppressing vagus nerve activity in a rat model. Secondly, we examined if ibuprofen absorption in rats during vagal suppression and in humans experiencing dental pain is improved by enhancing disintegration and dissolution rate of the administered formulation. METHODS: Vagal suppression was achieved in rats by administering 20 mg/kg propantheline i.p. 2 h and 1 h before gastric gavage of 20 mg/kg ibuprofen as small crushed pieces of a regular release and a fast-dissolving ibuprofen caplets. In humans, after surgical removal of wisdom teeth and emergence of pain, 2 A 200 mg ibuprofen as regular released (n = 14) and fast-dissolving (n = 12) caplets were administered. Serial blood sample were collected for bioavailability studies. RESULTS: Vagal suppression resulted in significantly decreased absorption rate of ibuprofen enantiomers following administration of the regular release but not after fast-dissolving formulation. Human dental pain was associated with significantly slower absorption of ibuprofen enantiomers from the regular released as compared with the fast-dissolving caplets. Within the first hour post-dose the area under the plasma drug concentration-time curve was raised to 2.7-fold (p < 0.05) after the fast-dissolving as compared with the regular release formulations. There was a 1-h difference in the peak concentration time (tmax) between the two caplets. CONCLUSION: Impaired drug absorption appears to be due to slow disintegration and dissolution encountered during pain episodes.
Asunto(s)
Ibuprofeno/uso terapéutico , Dolor/tratamiento farmacológico , Absorción/efectos de los fármacos , Administración Oral , Adulto , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/química , Analgésicos no Narcóticos/farmacocinética , Animales , Área Bajo la Curva , Sistemas de Liberación de Medicamentos , Femenino , Vaciamiento Gástrico/efectos de los fármacos , Semivida , Humanos , Ibuprofeno/sangre , Ibuprofeno/farmacocinética , Masculino , Dolor/fisiopatología , Dimensión del Dolor/métodos , Ratas , Ratas Sprague-Dawley , Índice de Severidad de la Enfermedad , Método Simple Ciego , Solubilidad , Estereoisomerismo , Comprimidos , Factores de Tiempo , Extracción Dental/métodos , Nervio Vago/efectos de los fármacos , Nervio Vago/fisiopatologíaRESUMEN
BACKGROUND AND PURPOSE: Inflammation elevates plasma verapamil concentrations but diminishes pharmacological response. Angiotensin II is a pro-inflammatory mediator. We examined the effect of angiotensin II receptor blockade on the pharmacokinetics and pharmacodynamics of verapamil, as well as the binding properties and amounts of its target protein in calcium channels, in a rat model of inflammation. EXPERIMENTAL APPROACH: We used 4 groups of male Sprague-Dawley rats (220-280 g): inflamed-placebo, inflamed-treated, control-placebo and control-treated. Inflammation as pre-adjuvant arthritis was induced by injecting Mycobacterium butyricum on day 0. From day 6 to 12, 30 mg kg(-1) oral valsartan or placebo was administered twice daily. On day 12, a single oral dose of 25 mg kg(-1) verapamil was administered and prolongation of the PR interval measured and plasma samples collected for verapamil and nor-verapamil analysis. The amounts of the target protein Ca(v)1.2 subunit of L-type calcium channels in heart was measured by Western blotting and ligand binding with (3)H-nitrendipine. KEY RESULTS: Inflammation reduced effects of verapamil, although plasma drug concentrations were increased. This was associated with a reduction in ligand binding capacity and amount of the calcium channel target protein in heart extracts. Valsartan significantly reversed the down-regulating effect of inflammation on verapamil's effects on the PR interval, and the lower level of protein binding and the decreased target protein. CONCLUSIONS AND IMPLICATIONS: Reduced responses to calcium channel blockers in inflammatory conditions appeared to be due to a reduced amount of target protein that was reversed by the angiotensin II antagonist, valsartan.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Bloqueadores de los Canales de Calcio/farmacocinética , Inflamación/metabolismo , Tetrazoles/farmacología , Valina/análogos & derivados , Animales , Western Blotting , Proteína C-Reactiva/análisis , Canales de Calcio Tipo L/análisis , Canales de Calcio Tipo L/metabolismo , Interacciones Farmacológicas , Masculino , Nitrendipino/metabolismo , Ratas , Ratas Sprague-Dawley , Valina/farmacología , Valsartán , Verapamilo/análogos & derivados , Verapamilo/farmacocinética , Verapamilo/farmacologíaRESUMEN
Wandering spleens are rare clinical entities found more commonly in females. We report a young female patient found to harbour a pelvic spleen. The literature regarding this rare ectopia is reviewed. The wandering spleen should be considered in the differential diagnosis of pelvic masses.
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Coristoma/diagnóstico por imagen , Ligamentos/anomalías , Cavidad Peritoneal/anomalías , Bazo , Dolor Abdominal/etiología , Adulto , Apendicitis/complicaciones , Apendicitis/diagnóstico , Apendicitis/cirugía , Coristoma/cirugía , Femenino , Humanos , Ligamentos/diagnóstico por imagen , Cavidad Peritoneal/diagnóstico por imagen , Flujo Sanguíneo Regional , Arteria Esplénica/anomalías , Arteria Esplénica/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Ultrasonografía DopplerRESUMEN
Solid pseudopapillary neoplasms of the pancreas (SPNP) are rare pancreatic tumors that occur predominantly in young women, with very few cases reported in men. While the origin of the tumor may be unclear, it is characterized by a distinct histological appearance and a clinical course highlighting its low malignant potential. SPNP have an excellent prognosis and are potentially curable provided they are managed appropriately by complete surgical resection. In the rare instances where metastatic disease is encountered, surgical debulking has been shown to prolong survival. The role of chemotherapy and radiation therapy in the management of SPNP is still controversial. We report here on an unusual occurrence of SPNP in the area of the head of the pancreas in a 12-year-old female treated by pancreatico-duodenectomy, together with a review of the literature.
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Neoplasias Pancreáticas/cirugía , Niño , Femenino , Humanos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Pancreaticoduodenectomía , Pronóstico , Tomografía Computarizada por Rayos XAsunto(s)
Suplementos Dietéticos/análisis , Suplementos Dietéticos/normas , Etiquetado de Medicamentos , Glucosamina/análisis , Administración Oral , Animales , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Líquida de Alta Presión/veterinaria , Etiquetado de Medicamentos/normas , Enfermedades de los Caballos/tratamiento farmacológico , Caballos , Artropatías/tratamiento farmacológico , Artropatías/veterinaria , Osteoartritis/tratamiento farmacológico , Osteoartritis/veterinaria , Control de CalidadRESUMEN
This study aims at evaluating trauma care at the American University of Beirut Medical Centre (AUB-MC) and comparing it to the norms established by the Major Trauma Outcome Study (MTOS). From January 2001 until January 2003, data necessary to calculate probability of survival using the Trauma Injury Severity Score methodology were collected. M, W, Z, Ws and Zs statistics were calculated to compare outcome at AUB-MC to the MTOS dataset. A total of 873 patients were included in the study. W statistics was calculated at 0.35 with Z score for the overall sample of 0.081 indicating that there was no statistically significant difference in survival between this group and the MTOS group. In a developing country a hospital achieves trauma outcomes similar to the MTOS dataset. Further studies looking at trauma care in Lebanon as a whole are needed.
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Países en Desarrollo/estadística & datos numéricos , Índices de Gravedad del Trauma , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Hospitales Universitarios/estadística & datos numéricos , Humanos , Lactante , Líbano/epidemiología , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Pronóstico , Análisis de Supervivencia , Heridas y Lesiones/mortalidadRESUMEN
BACKGROUND: Total mesorectal excision (TME) offers the lowest reported rates of local recurrence and the best survival results in patients with rectal cancer. However, the laparoscopic approach to resection for colorectal cancer remains controversial due to fears that oncologic principles will be compromised. We assessed the feasibility, safety and long-term outcome of laparoscopic rectal cancer resections following the principles of TME. The aim of this study was to evaluate the perioperative outcome and long-term results of laparoscopic TME. METHODS: We reviewed the prospective database of 102 consecutive unselected patients undergoing laparoscopic TME for rectal cancer between November 1991 and December 2000. Follow-up was done through office charts or direct patient contact. Recurrence and survival curves were generated by the Kaplan-Meier method. RESULTS: Laparoscopic TME was completed successfully in 99 patients, whereas conversion to an open approach was required in three cases (3%). The overall morbidity and mortality rates were 27% and 2%, respectively, with an overall anastomotic leak rate of 17%. Of the 102 patients, four were excluded from the oncologic evaluation because final pathology was not confirmatory (two had anal canal squamous cell carcinoma and two had villous adenoma with dysplasia). In 90 of the 98 remaining patients (91.8%), the resection was considered curative. The remainder had a palliative resection due to synchronous metastatic disease or locally advanced disease. Mean follow-up was 36 months (range, 6-96). There were no trocar site recurrences. The local recurrence rate was 6%, and the cancer-specific survival of all curatively resected patients was 75% at 5 years. The overall survival rate of all curatively resected patients was 65% at 5 years; mean survival time was 6.23 years (95% confidence interval [CI], 5.39-7.07). CONCLUSION: Laparoscopic TME is feasible and safe. The laparoscopic approach to the surgical treatment of operable rectal cancer does not seem to entail any oncologic disadvantages.
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Carcinoma de Células Escamosas/cirugía , Laparoscopía/métodos , Neoplasias del Recto/cirugía , Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/radioterapia , Quimioterapia Adyuvante , Terapia Combinada , Bases de Datos Factuales , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Laparoscopía/estadística & datos numéricos , Tablas de Vida , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Cuidados Paliativos , Complicaciones Posoperatorias , Radioterapia Adyuvante , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/mortalidad , Neoplasias del Recto/radioterapia , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
In this survey, Fusarium oxysporum was isolated from roots infected plants and was shown to be pathogenic. Experiment were carried out with seven antagonistic bacteria. Based on biochemical, Physiological and morphological tests, isolates B-120, B-32, B-28 and B-22 were identified as Bacillus subtilis and isolates Pf-100, Pf-10 and CHAO as Pseudomonas fluorescens. In greenhouse studies, only isolate B-120 (Less than benomyl) reduced Fusarium wilt of chickpea in both seed and soil treatments. The application of antagonistic bacteria had no different effects on plant growth factors. Soil treatment of bacteria had a better effects on plant growth than that of bacterial seed treatment. The use of antagonists (B-120, B-28, B-120 and CHAO) in combination had no significant effect on plant growth factors and reduction wilt disease than that each isolate was applied individually.
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Bacillus subtilis/crecimiento & desarrollo , Fusarium/patogenicidad , Control Biológico de Vectores/métodos , Enfermedades de las Plantas/microbiología , Raíces de Plantas/microbiología , Pseudomonas fluorescens/crecimiento & desarrollo , Desarrollo de la Planta , Raíces de Plantas/crecimiento & desarrollo , Brotes de la Planta/microbiología , Microbiología del SueloRESUMEN
Laparoscopic cholecystectomy (LC) is now widely accepted as the modality of choice for the treatment of symptomatic uncomplicated cholelithiasis. The application of the laparoscopic technique in the setting of acute cholecystitis (AC) is more controversial. The precise role as well as the potential benefits of LC in the treatment of the acutely inflamed gallbladder have not been clearly established through large clinical series. The aim of our study was to assess the feasibility, safety, benefits, and specific complications of the laparoscopic approach in patients with AC. A retrospective chart analysis involving the patients admitted to two busy emergency digestive surgical units between October 1990 and December 1997 was carried out. Six hundred and nine patients meeting our criteria for AC were identified and evaluated. Overall complication rate was 15% with 12 postoperative bile leakages (1.97%) and 4 biliary tract injuries (BTI) (0.66%). The overall mortality rate was 0.66%. Local and overall complication rates were significantly correlated with the delay between the onset of acute symptoms and the operation but not the rate of general complications nor deaths. Our results demonstrate the safety and feasibility of LC in the setting of AC. Early cholecystectomy within 4 days is strongly recommended to minimize complications and increase the chances of a successful laparoscopic approach.
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Colecistectomía Laparoscópica , Colecistitis/cirugía , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Colecistectomía Laparoscópica/efectos adversos , Colecistectomía Laparoscópica/métodos , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
OBJECTIVE: To determine the safety and feasibility of performing telerobotic laparoscopic cholecystectomies. This will serve as a preliminary step toward the integration of computer-rendered three-dimensional preoperative imaging studies of anatomy and pathology onto the patient's own anatomy during surgery. SUMMARY BACKGROUND DATA: Computer-assisted surgery (CAS) increases the surgeon's dexterity and precision during minimally invasive surgery, especially when using microinstruments. Clinical trials have shown the improved microsurgical precision afforded by CAS in the minimally invasive setting in cardiac and gynecologic surgery. Future applications would allow integration of preoperative data and augmented-reality simulation onto the actual procedure. METHODS: Beginning in September 1999, CAS was used to perform cholecystectomies on 25 patients at a single medical center in this nonrandomized, prospective study. The operations were performed by one of two surgeons who had previous laboratory experience using the computer interface. The entire dissection was performed by the surgeon, who remained at a distance from the patient but in the same operating room. The operation was evaluated according to time of dissection, time of assembly/disassembly of robot, complications, immediate postoperative course, and short-term follow-up. RESULTS: Twenty of the 25 patients had symptomatic cholelithiasis, 1 had a gallbladder polyp, and 4 had acute cholecystitis. Twenty-four of the 25 laparoscopic cholecystectomies were successfully completed by CAS. There was one conversion to conventional laparoscopic cholecystectomy. Set-up and takedown of the robotic arms took a median of 18 minutes. The median operative time for dissection and the overall operative time were 25 and 108 minutes, respectively. There were no intraoperative complications. There was one postoperative complication of a suspected pulmonary embolus, which was treated with anticoagulation. All patients were tolerating diet at discharge. CONCLUSIONS: Laparoscopic cholecystectomy performed by CAS is safe and feasible, with operative times and patient recovery similar to those of conventional laparoscopy. At present, CAS cholecystectomy offers no obvious advantages to patients, but the potential advantages of CAS lie in its ability to convert the surgical act into digitized data. This digitized format can then interface with other forms of digitized data, such as pre- or intraoperative imaging studies, or be transmitted over a distance. This has the potential to revolutionize the way surgery is performed.
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Colecistectomía Laparoscópica/métodos , Robótica , Terapia Asistida por Computador , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Colecistitis/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Inflammation may influence response to pharmacotherapy. We investigated the effect of inflammation on response to sotalol, a beta-adrenergic receptor and potassium channel antagonist. Racemic sotalol (40 mg kg(-1)) was administered to healthy, acutely (interferonalpha 2a-induced) and chronically (Mycobacterium butyricum-induced adjuvant arthritis) inflamed male Sprague-Dawley rats (n=4 - 6/group). Another group of interferon-treated rats received 3 mg kg(-1) of anti-TNF antibody infliximab. Electrocardiogram (ECG) recorded and plasma sotalol concentration monitored for 6 h. The study was repeated in acutely inflamed rats following administration of stereochemically pure individual sotalol enantiomers [40 mg kg(-1) S (potassium channel blocker) or 20 mg kg(-1) R (beta-adrenergic/potassium channel blocker)]. Chronic arthritis was readily evident. Acute arthritis was associated with elevated segmented neutrophils and increased plasma nitrite and tumour necrosis factor (TNF) concentrations. Sotalol affected ECG in all rats. In both inflamed groups, however, response to sotalol in prolongation of QT interval (potassium channel sensitivity) was reduced. The effect of PR interval (beta-adrenergic activity) was also reduced following administration of the racemate and R-enantiomer. No significant differences in pharmacokinetics were observed between control and inflamed rats. Infliximab reduced nitrite and TNF concentrations and reversed the effect of acute inflammation on both PR and QT intervals. The reduced electrocardiographic responses to sotalol is likely due to the influence of inflammation on the action of the drug on both beta-adrenergic and potassium channel receptors secondary to over-expression of pro-inflammatory cytokines and/or nitric oxide. Our observation may have therapeutic consequences in all conditions where inflammatory mediators are increased.