RESUMEN
Decreasing blood viscosity has been proposed since the advent of hemodilution as a means for increasing perfusion in many pathological conditions, and increased plasma viscosity is associated with the presence of pathological conditions. However, experimental studies show that microvascular functions as represented by functional capillary density in conditions of significantly decreased viscosity is impaired, a problem corrected by increasing plasma and blood viscosity. Blood viscosity, primarily dependent on hematocrit (Hct) is a determinant of peripheral vascular resistance, and therefore blood pressure. In the healthy population Hct presents a variability, which is not reflected by the variability of blood pressure. This is due to a regulatory process at the level of the endothelium, whereby the increase of Hct (and therefore blood viscosity) leads to increased shear stress and the production of the vasodilator nitric oxide (NO), a finding supported by experimental studies showing that the acute increase of Hct lowers blood pressure. Studies that in the healthy population show that blood pressure and Hct have a weak positive correlation. However, when the effect of blood viscosity is factored out, blood pressure and Hct are negatively and significantly correlated, indicating that as blood viscosity increases, the circulation dilates. Conversely, lower Hct and blood viscosity conditions lead to a constricted circulation, associated with a condition of decreased NO bioavailability, and therefore a pro-inflammatory condition.
Asunto(s)
Viscosidad Sanguínea/fisiología , Hemodilución/métodos , Microcirculación/fisiología , Viscosidad Sanguínea/efectos de los fármacos , Fenómenos Fisiológicos Cardiovasculares , Hematócrito , Humanos , Hipertensión/sangre , Óxido Nítrico/sangre , Óxido Nítrico/metabolismo , Resistencia Vascular/efectos de los fármacosRESUMEN
Topological and geometrical characteristics of the anastomotic arteriolar network in cat sartorius muscle were studied. The vessels were dilated and filled with gelatin-ink solution and the muscle cleared with methylsalicylate. The analysis was done on 11 muscles and included 2297 vascular segments and 772 vascular loops classified according to their position within the network. On average, each muscle had 644 transverse arterioles arising from the anastomotic vessels. The length of vascular segments close to feeding arteries was greater than those located in the central region, while the number of transverse arterioles per unit length of arcade vessel showed an opposite tendency. Most vessel orders had similar diameters, except for the segments at the periphery of the muscle, which were significantly larger. No correlation was found between vessel length and diameter. Vascular loops located in the central part of the network were smaller, as assessed by area, perimeter, number of segments, segment length and number of branches. The variability of the parameters between muscles was smaller than variability within each muscle. We concluded that, in addition to the parameters previously reported, quantitative descriptions of anastomotic networks may be enhanced by considering certain topological aspects of microvessels. The separation of segments and loops according to the position in the network may reveal differences between muscles of different sizes and functions which would not be detected if the vessels were considered as a single group.
Asunto(s)
Gatos/anatomía & histología , Músculo Esquelético/irrigación sanguínea , Animales , Arteriolas/anatomía & histología , Arteriolas/fisiología , Flujo Sanguíneo RegionalRESUMEN
BACKGROUND: Thromboembolic events may be related to thrombotic deposition on prosthetic valves. In a left ventricular assist device (LVAD) that contains two porcine pericardial bioprosthetic valves in addition to significant associated biomaterial placement, this may be particularly true. Thrombotic deposits on valves removed from LVADs at autopsy or heart transplantation were scored to determine (1) the nature and location of valvular deposition, (2) whether deposition was related to thromboembolic events, (3) correlations between deposition and patient hemodynamic and coagulation parameters, and (4) implant time dependency. METHODS AND RESULTS: Novacor LVADs were implanted in 23 patients as a bridge to transplantation for 1 to 303 days. Photographs of the concave (downstream) and convex (upstream) side of the inflow and outflow valve were made at explant and later scored for (1) total thrombus area (10 = equivalent of cusp area), (2) percent of cusp area occupied by solid thrombus, (3) thrombus color (10 = dark red, 0 = white), and (4) average percent of valve strut height involved with thrombus (from a side view). The inflow valve was shown to have heavier and redder deposition than the outflow valve. This was also true for the concave versus the convex side. Heaviest deposition was seen on the inflow valve concave side, which rests within the LVAD pumping sac and may be subject to poor convection. Patients with neurological thromboembolic events (8/23) during implantation had heavier deposition on the inflow valve concave side (5.7 +/- 2.7 versus 4.6 +/- 2.2, P < .05). Pump volumetric output was also found to negatively correlate with thrombus area on this valve and side (r = -.61, P = .002). Platelet release (platelet factor 4) was correlated with thrombus involvement on the upstream (convex) side of the inflow valve (r = .82, P = .002). No significant dependence of deposition on the implant time was found. CONCLUSIONS: Valve thrombus deposition was related to thromboembolic events. Pump volumetric output and platelet release were found to be related to deposition. These results may have implications for the role of hemodynamics and platelet activation in thromboembolism associated with prosthetic valve placement in general.
Asunto(s)
Bioprótesis/efectos adversos , Prótesis Valvulares Cardíacas/efectos adversos , Corazón Auxiliar/efectos adversos , Trombosis/etiología , Diseño de Equipo , Hemodinámica , Humanos , Tromboembolia/fisiopatología , Trombosis/fisiopatologíaRESUMEN
Early thrombosis of artificial microvascular grafts (AMG, grafts < or = 2 mm internal diameter) prevents their reliable clinical use. The present studies were undertaken to examine the effect of hirudin, a thrombin-specific inhibitor, and of the F(ab')2 fragment of PG-1, a monoclonal antibody (MoAb) directed against guinea pig platelet membrane glycoprotein Ib (GPIb), on AMG patency in an animal model. One-centimeter long segments of expanded polytetrafluoroethylene (ePTFE), 0.88 mm internal diameter, were serially implanted as interposition grafts in the guinea pig femoral arterial systems bilaterally. A control group was treated with 0.5 mL saline intravenously (IV) 30 minutes before limb 1 and limb 2 graft implantation. Three experimental groups were treated with 0.5 mL saline IV before limb 1 graft implantation as an animal control and with either 0.5 mL saline containing 1.25 mg/kg IV PG-1 F(ab')2, (which inhibits ristocetin-induced platelet agglutination and von Willebrand factor binding), hirudin 1 mg/kg IV, or a combination of both agents before limb 2 graft implantation. GPIb inhibition, thrombin inhibition, and the combination resulted in a significant prolongation of AMG patency (P < .005). Whereas thrombin inhibition with hirudin prolonged AMG patency similar to that observed with GPIb inhibition, the combination of GPIb and thrombin inhibition provided the overall longest prolongation of AMG patency. These results indicate that both platelet membrane GPIb and thrombin play a role in AMG thrombosis.
Asunto(s)
Vasos Sanguíneos/trasplante , Glicoproteínas de Membrana Plaquetaria/metabolismo , Trombosis/etiología , Adenosina Trifosfato/farmacología , Animales , Anticuerpos Monoclonales , Cobayas , Hemostasis/efectos de los fármacos , Hirudinas/farmacología , Masculino , Microcirculación , Microscopía Electrónica , Agregación Plaquetaria/efectos de los fármacos , Glicoproteínas de Membrana Plaquetaria/antagonistas & inhibidores , Trombina/antagonistas & inhibidoresRESUMEN
Laser-assisted microvascular anastomoses can be performed more quickly than sutured anastomoses, yet manifest similar patency rates and tensile strength. This study was undertaken to determine if in vitro laser-assisted microvascular anastomoses could be created between human adult arteries (anterior tibial arteries), human placental arteries, and expanded polytetrafluoroethylene microconduits. A CO2 laser was applied in single or continuous bursts with a matrix of variables encompassing power P = 80 to 160 mW, spot size SS = 150 to 500 microns, and exposure time EXP = 1.0-second continuous exposure (n = 2 each composite setting). The endpoints measured to assess the ability to laser-weld vessels were morphologic appearance by scanning electron microscopy and bursting strength. Scanning electron microscopy revealed apparent fusion of human placental arteries and human adult arteries to expanded polytetrafluoroethylene microconduits at settings of P = 130 mW, SS = 300 microns, and EXP = 1.0 second, though bursting pressure at all settings was less than 10 mmHg. Laser-assisted microvascular anastomoses of human placental artery to human placental artery and human adult artery to human adult artery were successful at this setting, though bursting pressures of anastomoses incorporating placental vessels were significantly weaker than those created with adult tissue. The relative weakness of laser-assisted microvascular anastomoses incorporating placental arteries might be explained by qualitative or quantitative differences in vessel wall collagen, as seen in fetal tissue, and deserves further characterization.
Asunto(s)
Arterias/cirugía , Prótesis Vascular , Terapia por Láser , Microcirugia/métodos , Politetrafluoroetileno , Adulto , Anastomosis Quirúrgica , Arterias/ultraestructura , Fenómenos Biomecánicos , Humanos , Técnicas In Vitro , Microcirculación/cirugía , Microscopía Electrónica de Rastreo , Placenta/irrigación sanguíneaRESUMEN
The propensity for platelets to bind at a native vessel anastomosis is thought to be related to subendothelial exposure, the presence of suture material, and local flow disturbances. By using an artificial microvascular graft to artificial microvascular graft anastomosis model that mimics the geometry and topography of a native microvascular anastomosis but which eliminates the endothelial and subendothelial contributions, the influence of the normal anastomotic configuration alone on initial platelet deposition was measured. Anastomotic and immediate downstream platelet deposition was not augmented by the presence of the anastomotic configuration alone. This suggests that the enhanced initial platelet deposition in the region of a native vessel microanastomosis is primarily related to the presence of injured endothelium and exposed subendothelium rather than to flow disturbances.
Asunto(s)
Anastomosis Quirúrgica/métodos , Prótesis Vascular , Microcirugia/métodos , Agregación Plaquetaria/fisiología , Politetrafluoroetileno , Combinación de Medicamentos , Hemostáticos/química , Humanos , Radioisótopos de Indio , Microscopía Electrónica de Rastreo , Modelos Cardiovasculares , Palmitatos/química , Adhesividad Plaquetaria/fisiología , Recuento de Plaquetas , Politetrafluoroetileno/química , Reología , Propiedades de Superficie , Ceras/químicaRESUMEN
Initial platelet deposition (PD) in and around the region of a small-vessel anastomosis may set the stage for thrombosis and tissue loss. To study this problem, a human vessel model (human placental artery, HPA) has been designed to mimic the vascular injuries attendant on clinical microsurgery. To perform these studies, dissected lengths of human placental artery were treated to provide the following four types of injury: group I: control, dissected but otherwise uninjured (N = 5); group II: distal portion of vessel endothelium removed (N = 5); group III: central anastomosis, distal endothelium intact (N = 7); and group IV: central anastomosis, distal endothelium removed (N = 4). Vessels were perfused with 25 ml human whole blood for 17 +/- 5 s at an average shear rate of 536 s-1. Vessels in groups I to IV were segmented at 2-cm intervals, and the number of 111In-labeled platelets was measured. Data from the following groups of exposure zones were pooled and analyzed: endothelium intact, endothelium absent, anastomosis present, postanastomosis with endothelium intact, and postanastomosis with endothelium absent. Significant numbers of platelets were found to attach to intact endothelium, indicating that ischemia and microsurgical handling may augment platelet deposition to otherwise uninjured vessels. A similar degree of platelet deposition was measured after exposure of the subendothelium and perfusion, indicating that superficial subendothelial exposure in the absence of an additional prothrombotic stimulus may lead to no greater platelet deposition than occurs on slightly injured endothelium alone. Platelet deposition at anastomoses was strikingly elevated, although the anastomosis had no additive effect on platelet deposition to downstream endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Vasos Sanguíneos/fisiología , Adhesividad Plaquetaria , Procedimientos Quirúrgicos Vasculares , Anastomosis Quirúrgica , Vasos Sanguíneos/ultraestructura , Endotelio Vascular/fisiología , Humanos , Técnicas In Vitro , Microscopía Electrónica de Rastreo , Microcirugia , Placenta/irrigación sanguínea , Flujo Sanguíneo RegionalRESUMEN
Vasodilation of small blood vessels is controlled in part by the endothelium-derived relaxing factor (EDRF), which also inhibits platelet adhesion. Methylene blue (MB), which is occasionally applied directly to blood vessels during microsurgery to provide orientation and prevent torsion, is an irreversible inhibitor of the effects of endothelium-derived relaxing factor and may thereby augment both vasospasm and platelet responses. We have investigated the effects of the extravascular adventitial application of methylene blue on platelet deposition to human placental arteries (HPA) in the presence and absence of surgically induced vasospasm. A trend toward increased platelet deposition to human placental arteries was seen in each group but did not reach significance. The degree of platelet deposition to control human placental arteries suggests that the effects of methylene blue on platelet deposition may be dwarfed by the effects of surgical trauma and ischemia.
Asunto(s)
Arterias/efectos de los fármacos , Plaquetas/efectos de los fármacos , Azul de Metileno/farmacología , Óxido Nítrico/antagonistas & inhibidores , Vasoconstricción/efectos de los fármacos , Administración Tópica , Etidocaína/farmacología , Femenino , Humanos , Técnicas In Vitro , Azul de Metileno/administración & dosificación , Placenta/irrigación sanguínea , EmbarazoRESUMEN
The mechanism of platelet thrombus growth on an artificial surface is incompletely understood. While glycoprotein (GP)Ib and GPIIb/IIIa are required for normal attachment and thrombus formation on subendothelium, their roles in platelet deposition to artificial surfaces remain unclear. Using selected platelet inhibitors (aspirin [ASA], low molecular weight dextran, monoclonal antibodies 10E5 [v GPIIb/IIIa], and 6D1 [GPIb]) we examined the mechanism of platelet deposition to polyethylene (PE) surfaces under steady laminar and oscillatory flow conditions. Polyethylene-100 (PE-100) tubes (0.86 mm internal diameter) were perfused under steady laminar flow with citrated human whole blood reconstituted with 111indium-labeled platelets at 312 seconds-1 shear rate in the presence and absence of platelet inhibitors. The effect of oscillatory flow on platelet deposition was examined in a microwell system using 3/16-inch diameter discs of National Heart, Lung, and Blood Institute primary reference PE as the test surface. ASA and dextran did not significantly (P greater than .05) inhibit platelet deposition in laminar flow (not tested in oscillatory). Antibody 10E5 was a potent inhibitor (laminar less than 1%, P less than .0001, oscillatory less than 1.6%, P less than .01) of platelet deposition in both systems, and in this case, true adhesion (first attached layer) was blocked. Antibody 6D1 unexpectedly inhibited 70% of platelet deposition (P less than .01) in steady laminar flow and 56.5% in oscillatory flow (P less than .01). Scanning electron microscopy demonstrated platelets atop platelets in the controls, rare platelets in the 10E5 group, and a patchy monolayer of platelets in the 6D1 group. Transmission electron microscopy of cross-sections confirmed these observations. We conclude that the adhesion of the first platelet layer to an artificial surface requires GPIIb/IIIa. The data also suggest that GPIb is required for the development of the second layer in vertical platelet thrombus growth.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Plaquetas/fisiología , Adhesividad Plaquetaria , Inhibidores de Agregación Plaquetaria/farmacología , Glicoproteínas de Membrana Plaquetaria/fisiología , Adenosina Difosfato/sangre , Adenosina Trifosfato/sangre , Aspirina/farmacología , Plaquetas/citología , Plaquetas/efectos de los fármacos , Humanos , Técnicas In Vitro , L-Lactato Deshidrogenasa/sangre , Perfusión/instrumentación , Perfusión/métodos , Adhesividad Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Glicoproteínas de Membrana Plaquetaria/inmunologíaRESUMEN
Nine patients with extensive wounds of the hip joint due to chronic infection following total hip arthroplasty or internal fixation of fractures of the femoral head and neck have been treated by serial radical debridements to remove infected bone, contaminated remnants of bone cement, and the surrounding fibrotic soft tissues. The resultant deep cavity extending down to the acetabulum has then been obliterated with either pedicled muscle flaps or free muscle flaps. Subcutaneous or transpelvic transposition of rectus abdominis muscle flaps is preferred for smaller defects, but only the free latissimus dorsi muscle flap provides sufficient volume of tissue to obliterate the more extensive hip defects. Systemic antibiotics have been continued only for a short-term course of 14 days postoperatively. There has been no recurrence of infection, with follow-up ranging between 6 months and 3 1/4 years. One patient has undergone reimplantation of a second custom hip prosthesis into the vascularized bed of a free latissimus dorsi muscle flap.
Asunto(s)
Desbridamiento , Prótesis de Cadera/efectos adversos , Colgajos Quirúrgicos/métodos , Infección de la Herida Quirúrgica/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infección de la Herida Quirúrgica/etiologíaRESUMEN
Rapid occlusion of artificial microvascular grafts (AMGs; less than or equal to 2-mm diameter) by platelet-rich thrombi prevents the clinical use of AMGs in cardiac, vascular, and plastic surgery. Since present antiplatelet agents are unable to assure AMG patency, we have studied the role of specific platelet membrane-glycoprotein blockade on platelet retention by AMGs. In a customized in vitro perfusion chamber, retention on polytetrafluoroethylene (PTFE) AMGs (1.0-mm i.d.) of indium-111-labeled platelets in human whole blood was measured in the presence and absence of inhibitors. Specific blockade of platelet membrane glycoprotein (Gp) IIb/IIIa was achieved using monoclonal antibody 10E5 (10 micrograms/ml) and the peptide GRGDS (Gly-Arg-Gly-Asp-Ser, 0.75 mM). These inhibited 98% and 35%, respectively, of platelet retention under circumstances in which aspirin (7 mM) and dextran (4 mg/ml) inhibited 19% and 18%, respectively, of platelet retention. Nonspecific immunoglobulin G F(ab')2 (10 micrograms/ml) and nonspecific peptide (GGDA; Gly-Gly-Asp-Ala, 0.75 mM), used as control reagents, were ineffective in this setting. Monoclonal antibody 6D1 (10 micrograms/ml), which blocks platelet membrane GpIb, prevented 82% of platelet retention on PTFE. These doses of 10E5 and GRGDS completely inhibited platelet aggregation in response to 20 microM ADP, and the dose of 6D1 completely inhibited ristocetin-induced platelet agglutination. The aspirin dose prevented the second phase of ADP-induced aggregation. These data indicate that not only does initial platelet adhesion to PTFE require GpIIb/IIIa but also that GpIb plays a significant role in the early stages of platelet retention on PTFE AMGs.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Plaquetas/fisiología , Prótesis Vascular , Fibrinógeno/fisiología , Microcirculación , Glicoproteínas de Membrana Plaquetaria/fisiología , Adenosina Difosfato/farmacología , Aspirina/farmacología , Dextranos/farmacología , Humanos , Microscopía Electrónica de Rastreo , Fragmentos de Péptidos/farmacología , Adhesividad Plaquetaria , Agregación Plaquetaria , Inhibidores de Agregación Plaquetaria/farmacología , Glicoproteínas de Membrana Plaquetaria/antagonistas & inhibidores , Glicoproteínas de Membrana Plaquetaria/inmunología , Politetrafluoroetileno , Ristocetina/farmacologíaRESUMEN
Norwalk virus infection was sought in 48 US, 49 Puerto Rican, and 27 Mexican adults attending medical school in Guadalajara (Mexico) who were enrolled in a 2-year longitudinal study. Serum specimens were collected quarterly and as acute- and convalescent-phase samples around episodes of gastroenteritis. The reciprocal Norwalk virus geometric mean titer (GMT) for Puerto Rican students (567) was significantly higher than that of the US students overall (294; P less than .001) and for four of nine quarterly periods. The reciprocal Norwalk GMT for Mexican students (748) was also significantly higher than that of the US students overall (P less than .001) and for seven of nine quarterly periods. The average percentage of students per year with seroconversions was 30%. The rate of Norwalk virus infection averaged 0.36 episodes per student-year. Symptoms of gastroenteritis associated with seroconversion occurred in 45% of students. Preexisting serum antibody did not protect against subsequent Norwalk virus infection in these subjects. All student groups had similar rates of infection and symptomatic gastroenteritis.
Asunto(s)
Gastroenteritis/epidemiología , Virosis/epidemiología , Adulto , Anticuerpos Antivirales/sangre , Antígenos Virales/análisis , Antígenos Virales/sangre , Gastroenteritis/etnología , Humanos , Estudios Longitudinales , México/epidemiología , Virus Norwalk/inmunología , Puerto Rico/etnología , Estaciones del Año , Estados Unidos/etnología , Virosis/etnologíaRESUMEN
A method is described to quantify the shape and orientation of vascular loops (arcades). Shape is characterized by an ellipticity factor, calculated from area and perimeter values. Orientation is measured as the angle formed by the great axis of the loop with the muscle fibers. These parameters were calculated for 772 arteriolar loops of the cat sartorius muscle. The results show that, on the average, the ellipticity factor is a linear function of the number of segments. The observed values change in the opposite direction from the expected values for regular polygons. Simple calculations are presented to rectify this discrepancy. Most loops are oriented parallel to the muscle fibers.
Asunto(s)
Gatos/anatomía & histología , Músculos/irrigación sanguínea , Animales , Arterias/anatomía & histología , Femenino , MasculinoRESUMEN
In a randomized, double-blind, placebo-controlled trial, 227 US adults with acute diarrhea in Mexico received a single dose of sulfamethoxazole and trimethoprim (1600/320 mg) or 3 days of therapy with loperamide hydrochloride (4-mg loading dose, then 2 mg orally after each loose stool), sulfamethoxazole-trimethoprim (800/160 mg orally twice daily), or the combination of both. Subjects treated with the combination had the shortest average duration of diarrhea compared with the placebo group (1 hour vs 59 hours), took the least amount of loperamide after the loading dose (3.8 mg), and had the shortest duration of diarrhea associated with fecal leukocytes or blood-tinged stools (4.5 hours). A single dose of sulfamethoxazole-trimethoprim was also efficacious (28 vs 59 hours), but loperamide alone was significantly effective only when treatment failures were treated with antibiotics (33 vs 58 hours). The combination of sulfamethoxazole-trimethoprim plus loperamide can be highly recommended for the treatment of most patients with traveler's diarrhea.
Asunto(s)
Diarrea/tratamiento farmacológico , Loperamida/uso terapéutico , Piperidinas/uso terapéutico , Viaje , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Adulto , Método Doble Ciego , Quimioterapia Combinada , Fluidoterapia , Humanos , Loperamida/administración & dosificación , México , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Combinación Trimetoprim y Sulfametoxazol/administración & dosificación , Estados Unidos/etnologíaRESUMEN
During the months of July 1977 and July 1985, students from the United States participated in a double-blind, placebo-controlled trial examining the effectiveness of liquid bismuth subsalicylate (BSS) (1977) and two dosages of the tablet formulation of BSS (1985) in preventing diarrhea while in Guadalajara, Mexico. In the first study, 62 subjects received BSS for 3 weeks at a dosage of 60 mL four times daily (4.2 g of BSS/d) compared with 66 students receiving an oral placebo at a similar dosage schedule. In the second study, 51 students took two tablets four times daily (2.1 g of BSS/d), 63 took one tablet four times daily (1.05 g of BSS/d), and 58 took a placebo (two tablets taken four times daily), each for 3 weeks. In the initial study, 14 (23%) BSS-treated subjects developed diarrhea compared with 40 (61%) placebo-tested persons (P less than .0001). In the second trial, seven (14%) subjects taking two tablets of BSS four times daily, 15 (24%) taking one tablet of BSS four times daily, and 23 (40%) receiving placebo tablets experienced diarrhea (P less than .001 for the higher dose). The percent protection provided by BSS was 62% for the group that received 4.2 g/d, 65% for 2.1 g/d, and 40% for 1.05 g/d, when compared with the corresponding placebo group. In cases in which stools were analyzed, seven (24%) of 29 BSS-treated subjects who had diarrhea had a detectable enteric pathogen, compared with 35 (59%) of 59 of those randomized to receive a placebo. BSS was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Bismuto/uso terapéutico , Diarrea/prevención & control , Compuestos Organometálicos/uso terapéutico , Salicilatos/uso terapéutico , Adulto , Bismuto/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , México , Compuestos Organometálicos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Salicilatos/efectos adversos , Viaje , Estados UnidosRESUMEN
Within 48 hours of arrival in Mexico, 182 US students participated in a study to compare the efficacy of two dosages of bismuth subsalicylate (262 mg per tablet) as a prophylactic agent against diarrhea. The students were randomly assigned to receive two tablets (high dose) or one tablet (low dose) of bismuth subsalicylate four times daily or a placebo four times daily during a three-week period. Among these completing the trial, diarrhea (four or more unformed stools in 24 hours or three in eight hours, plus one other symptom) occurred in seven (14%) of 51 receiving the high-dose regimen compared with 15 (24%) of 63 receiving the low-dose regimen and 23 (40%) of 58 in the placebo group. Protection rates were 65% for high-dose and 40% for low-dose bismuth subsalicylate. Diarrhea caused by enterotoxigenic Escherichia coli was found in one student receiving the high-dose regimen, in no students receiving the low-dose regimen, and in seven placebo-treated subjects. Bismuth subsalicylate was well tolerated; the most common side effects were blackening of tongues and stools. Bismuth subsalicylate use in both dosages was associated with tinnitus at a low, clinically insignificant frequency of 1.2 days per 100 days of treatment. The dosage of two tablets of bismuth subsalicylate four times daily (2.1 g/d) appears to be a safe and effective means of reducing the occurrence of travelers' diarrhea among persons at risk for periods up to three weeks.
Asunto(s)
Bismuto , Diarrea/prevención & control , Compuestos Organometálicos/uso terapéutico , Salicilatos/uso terapéutico , Viaje , Adulto , Diarrea/microbiología , Humanos , México , Compuestos Organometálicos/administración & dosificación , Compuestos Organometálicos/efectos adversos , Probabilidad , Distribución Aleatoria , Salicilatos/administración & dosificación , Salicilatos/efectos adversos , ComprimidosRESUMEN
The efficacy of BW942C, a novel enkephalinlike pentapeptide antidiarrheal agent, was compared with the efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) and the combination of the two agents in a placebo-controlled trial of the 72-h treatment of acute diarrhea. Subjects with diarrhea but without bloody stools or fever greater than 102 degrees F (38.9 degrees C) were enrolled. Administered to 134 U.S. adults with diarrhea that developed shortly after their arrival in Guadalajara, Mexico, BW942C was more efficacious than TMP-SMX in relieving diarrhea and cramps in the first 12 h of therapy, especially among subjects with diarrhea caused by enterotoxigenic E. coli. In the BW942C treatment group, 25% of subjects eventually took additional therapy because their diarrhea did not respond to BW942C alone. Neurological side effects such as dizziness and light-headedness occurred more frequently among BW942C-treated subjects. Therapy for 3 days with TMP-SMX provided lasting relief comparable with previously reported 5-day therapy. Use of the combination of both agents provided the benefits of prompt relief afforded by BW942C and lasting relief afforded by TMP-SMX. BW942C might prove to be an agent suitable for the treatment of acute diarrhea, with TMP-SMX reserved for treatment of those who do not respond adequately. The empiric use of the combination of BW942C and TMP-SMX appears appropriate for the treatment of severe nondysenteric disease.
Asunto(s)
Antidiarreicos/uso terapéutico , Diarrea/tratamiento farmacológico , Encefalina Metionina/análogos & derivados , Encefalinas , Sulfametoxazol/uso terapéutico , Trimetoprim/uso terapéutico , Antidiarreicos/efectos adversos , Ensayos Clínicos como Asunto , Método Doble Ciego , Combinación de Medicamentos/efectos adversos , Combinación de Medicamentos/uso terapéutico , Encefalina Metionina/efectos adversos , Encefalina Metionina/uso terapéutico , Heces/microbiología , Femenino , Humanos , Masculino , México , Distribución Aleatoria , Sulfametoxazol/efectos adversos , Viaje , Trimetoprim/efectos adversos , Combinación Trimetoprim y Sulfametoxazol , Estados UnidosRESUMEN
Adherence to HEp-2 tissue culture cells has been proposed as a virulence characteristic of enteropathogenic Escherichia coli (EPEC). A preliminary study revealed that E. coli that adhered to HEp-2 cells, but did not produce conventional enterotoxins and did not belong to recognized EPEC serogroups, could be isolated from adults from the United States who acquired diarrhea in Mexico. The purpose of this study was to determine the prevalence of these enteroadherent E. coli (EAEC) in 188 travelers with diarrhea and in 92 well travelers. EAEC were found in 14.9% of patients with diarrhea and in 7.6% of well individuals. Compared with well travelers, patients with diarrhea in whom no recognized enteropathogen could be identified had a 30.4% prevalence of EAEC (P less than .0003). These results further support our finding that EAEC are associated with diarrhea in travelers to Mexico and may help to explain the effect of antibiotics in the prevention and therapy for travelers' diarrhea in patients with no recognized bacterial enteropathogens.