RESUMEN
The co-ion and counter-ion sorption of monovalent (Na+, K+, Cl- and NO3-) and divalent ions (Ca2+ and SO42-) in commercial Neosepta ion exchange membranes were systemically studied in both single and binary salt systems. The new generation of Neosepta cation exchange membrane (CSE) showed a significant difference in water uptake and co-ion sorption compared to the earlier generation (CMX). Use of the Manning model confirmed that there were significant differences between these membranes, with the estimated value of the Manning parameter changing from 1.0 ± 0.1 for CMX to 2.8 ± 0.5 for CSE. There were fewer differences between the two Neosepta anion exchange membranes, AMX and ASE. In single salt solutions, potassium sorbed most strongly into the cation exchange membranes, but in binary salt mixtures, calcium dominated due to Donnan exclusion at low concentrations. While these trends were expected, the sorption behaviour in the anion exchange membranes was more complex. The water uptake of both AMX and ASE was shown to be the greatest in Na2SO4 solutions. This strong water uptake was reflected in strong sorption of sulphate ions in a single salt solution. Conversely, in a binary salt mixture with NaCl, sulphate sorption fell significantly at higher concentrations. This was possibly caused by ion pairing within the solution, as well as the strongly hydrophobic nature of styrene in the charged polymer. Water uptake was lowest in NaNO3 solutions, even though sorption of the nitrate ion was comparable to that of chloride in these single salt solutions. In the binary mixture, nitrate was absorbed more strongly than chloride. These results could be due to the low surface charge density of this ion allowing it to bond more strongly with the hydrophobic polymeric backbone at the exclusion of water and other ions.
Asunto(s)
Purificación del Agua , Cationes , Intercambio Iónico , Resinas de Intercambio Iónico , AguaRESUMEN
Critical illness trials involving genetic data collection are increasingly commonplace and pose challenges not encountered in less acute settings, related in part to the precipitous, severe and incapacitating nature of the diseases involved. We performed a systematic literature review to understand the nature of such studies conducted to date, and to consider, from an ethical perspective, potential barriers to future investigations. We identified 79 trials enrolling 24 499 subjects. Median (interquartile range) number of participants per study was 263 (116.75-430.75). Of these individuals, 16 269 (66.4%) were Caucasian, 1327 (5.4%) were African American, 1707 (7.0%) were Asian Pacific Islanders and 139 (0.6%) were Latino. For 5020 participants (20.5%), ethnicity was not reported. Forty-eight studies (60.8%) recruited subjects from single centers and all studies examined a relatively small number of genetic markers. Technological advances have rendered it feasible to conduct clinical studies using high-density genome-wide scanning. It will be necessary for future critical illness trials using these approaches to be of greater scope and complexity than those so far reported. Empirical research into issues related to greater ethnic inclusivity, accuracy of substituted judgment and specimen stewardship may be essential for enabling the conduct of such trials.
Asunto(s)
Investigación Biomédica/ética , Enfermedad Crítica , Variación Genética , Insuficiencia Multiorgánica/genética , Selección de Paciente/ética , Ensayos Clínicos Controlados Aleatorios como Asunto/ética , Sepsis/genética , Choque Séptico/genética , Adulto , Negro o Afroamericano , Asiático , Hispánicos o Latinos , Humanos , Consentimiento Informado/ética , Insuficiencia Multiorgánica/etnología , Sepsis/etnología , Choque Séptico/etnología , Población BlancaRESUMEN
Glassy, disubstituted acetylene-based polymers exhibit extremely high gas permeabilities and high vapor/gas selectivities, which is quite unusual for conventional glassy polymers such as polysulfone. Diffusion coefficients of poly[1-phenyl-2-[p-(trimethylsilyl)phenyl]acetylene] (PTMSDPA) and poly[diphenylacetylene] (PDPA) were obtained using both molecular simulation and experimental techniques. PTMSDPA, a disubstituted glassy acetylene-based polymer, exhibits higher diffusivity than its desilylated analogue, PDPA. Simulation results are in good agreement with experimental data. Cavity size (free volume) distributions of both polymers are also obtained using an energetic-based algorithm (in't Veld et al., J. Phys. Chem. B 2000, 104, 12028) developed recently. Larger cavities in PTMSDPA contribute to its higher diffusivity, and higher permeability.
RESUMEN
Polymer nanocomposites continue to receive tremendous attention for application in areas such as microelectronics, organic batteries, optics, and catalysis. We have discovered that physical dispersion of nonporous, nanoscale, fumed silica particles in glassy amorphous poly(4-methyl-2-pentyne) simultaneously and surprisingly enhances both membrane permeability and selectivity for large organic molecules over small permanent gases. These highly unusual property enhancements, in contrast to results obtained in conventional filled polymer systems, reflect fumed silica-induced disruption of polymer chain packing and an accompanying subtle increase in the size of free volume elements through which molecular transport occurs, as discerned by positron annihilation lifetime spectroscopy. Such nanoscale hybridization represents an innovative means to tune the separation properties of glassy polymeric media through systematic manipulation of molecular packing.
RESUMEN
IL-1 is a pivotal mediator of the immune response and has been implicated in inflammatory and infectious diseases. As a consequence, the administration of IL-1 receptor antagonist (IL-1ra), a recombinantly synthesised endogenous inhibitor of IL-1, has appeal as a therapeutic strategy in these conditions. To date, the largest clinical experiences with IL-1ra have been in the setting of sepsis and rheumatoid arthritis (RA). Like other anti-inflammatory agents that target a specific mediator, IL-1ra was found to lack efficacy when given in conjunction with standard therapy in patients with sepsis and septic shock. In contrast, recent studies enrolling patients with RA suggest that IL-1ra significantly ameliorates disease activity and retards joint destruction. Whether the respective lack of efficacy and success of IL-1ra in these two diseases is a result of differences in the pathologic processes involved, or reflects the nature in which the clinical studies were conducted, is unclear. Further, the effectiveness of IL-1ra compared to other anticytokine and conventional treatments in RA remains to be clarified. Nonetheless, the recent finding that IL-1ra has the ability to favourably influence a chronic inflammatory disease supports the hypothesis that inhibition of a single mediator of the immune response may have clinical impact.
Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Receptores de Interleucina-1/antagonistas & inhibidores , Sepsis/tratamiento farmacológico , Sialoglicoproteínas/uso terapéutico , Artritis Reumatoide/inmunología , Ensayos Clínicos como Asunto , Humanos , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Proteína Antagonista del Receptor de Interleucina 1 , Receptores de Interleucina-1/inmunología , Sepsis/inmunología , Sialoglicoproteínas/inmunología , Resultado del TratamientoAsunto(s)
Ensayos Clínicos como Asunto/normas , Enfermedad Crítica/mortalidad , Enfermedad Crítica/terapia , Aspirina/análogos & derivados , Aspirina/uso terapéutico , Sustitutos Sanguíneos/uso terapéutico , Hemoglobinas/uso terapéutico , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Choque Hemorrágico/tratamiento farmacológico , Choque Séptico/tratamiento farmacológico , omega-N-Metilarginina/uso terapéuticoRESUMEN
Warfarin use is complicated by an erratic dose response. Warfarin is metabolized by two distinct subfamilies of the cytochrome P450 (CYP) complex. We describe two siblings with extreme sensitivity to warfarin who share an unusual CYP genotype. These individuals illustrate both the importance of genetics in influencing the metabolism of warfarin as well as the potential utility of genetic testing as a guide to prescribing this medication.
Asunto(s)
Hidrocarburo de Aril Hidroxilasas , Sistema Enzimático del Citocromo P-450/genética , Hipersensibilidad a las Drogas/genética , Esteroide 16-alfa-Hidroxilasa , Warfarina/efectos adversos , Anciano , Anciano de 80 o más Años , Citocromo P-450 CYP2A6 , Salud de la Familia , Femenino , Humanos , Oxigenasas de Función Mixta/genética , Núcleo Familiar , Polimorfismo Genético , Análisis de Secuencia de ADN , Esteroide Hidroxilasas/genética , Warfarina/farmacocinéticaRESUMEN
OBJECTIVE: To determine the relative cost-effectiveness of percutaneous dilational tracheostomy (PDT) and surgical tracheostomy (ST) in critically ill patients. DESIGN: Prospective randomized study. SETTING: Medical, surgical, and coronary intensive care units at Barnes-Jewish Hospital, a tertiary care medical center. PATIENTS: Eighty critically ill mechanically ventilated patients requiring elective tracheostomy. INTERVENTIONS: Randomization to either PDT performed in the intensive care unit or ST performed in the operating room. MEASUREMENTS AND MAIN RESULTS: Treatment groups were well matched with respect to age (PDT, 65.44 +/- 2.82 [mean +/- se] years; ST, 61.4 +/- 2.89 years, p = Ns), gender (PDT, 45% males; ST, 47.5% males, p = NS), severity of illness (Acute Physiology and Chronic Health Evaluation II score: PDT, 16.87 +/- 0.84; ST, 17.88 +/- 0.92, p = NS), and principle diagnosis. PDT was performed more quickly (PDT, 20.1 +/- 2.0 mins; ST, 41.7 +/- 3.9 mins, p < .0001) and was associated with lower patient charges than ST (total patient charges: PDT, 1,569 dollars +/- 157 dollars vs. ST, 3,172 dollars +/- 114 dollars; equipment/supply charges: PDT, 688 dollars +/- 103 dollars vs. ST, 1,526 dollars +/- 87 dollars; professional charges: PDT, 880 dollars +/- 54 dollars vs. ST, 1,647 dollars +/- 50 dollars; p < .0001 for all). There were no differences in days intubated before tracheostomy (PDT, 12.7 +/- 1.1 days; ST, 15.6 +/- 1.9, p = .20), intensive care unit length of stay (PDT, 24.5 +/- 2.5 days; ST, 28.5 +/- 3.1 days, p = .33), or hospital length of stay (PDT 49.7 +/- 4.2 days; ST, 43.7 +/- 3.5 days, p = .28) when we compared these two techniques. CONCLUSIONS: PDT is a cost-effective alternative to ST. The reduction in patient charges associated with PDT in this study resulted from the procedure being performed in the intensive care unit, thus eliminating the need for operating room facilities and personnel. PDT may become the procedure of choice for electively establishing tracheostomy in the appropriately selected patient who requires long-term mechanical ventilation.
Asunto(s)
Cuidados Críticos , Traqueostomía/métodos , Análisis Costo-Beneficio , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Respiración Artificial , Traqueostomía/economíaAsunto(s)
Anticoagulantes/efectos adversos , Hidrocarburo de Aril Hidroxilasas , Sistema Enzimático del Citocromo P-450/genética , Hemorragia/inducido químicamente , Hemorragia/genética , Esteroide 16-alfa-Hidroxilasa , Esteroide Hidroxilasas/genética , Warfarina/efectos adversos , Anciano , Anciano de 80 o más Años , Femenino , Predisposición Genética a la Enfermedad , Humanos , PiernaRESUMEN
Patients with sepsis have impaired host defenses that contribute to the lethality of the disorder. Recent work implicates lymphocyte apoptosis as a potential factor in the immunosuppression of sepsis. If lymphocyte apoptosis is an important mechanism, specific subsets of lymphocytes may be more vulnerable. A prospective study of lymphocyte cell typing and apoptosis was conducted in spleens from 27 patients with sepsis and 25 patients with trauma. Spleens from 16 critically ill nonseptic (3 prospective and 13 retrospective) patients were also evaluated. Immunohistochemical staining showed a caspase-9-mediated profound progressive loss of B and CD4 T helper cells in sepsis. Interestingly, sepsis did not decrease CD8 T or NK cells. Although there was no overall effect on lymphocytes from critically ill nonseptic patients (considered as a group), certain individual patients did exhibit significant loss of B and CD4 T cells. The loss of B and CD4 T cells in sepsis is especially significant because it occurs during life-threatening infection, a state in which massive lymphocyte clonal expansion should exist. Mitochondria-dependent lymphocyte apoptosis may contribute to the immunosuppression in sepsis by decreasing the number of immune effector cells. Similar loss of lymphocytes may be occurring in critically ill patients with other disorders.
Asunto(s)
Apoptosis/inmunología , Linfocitos B/patología , Linfocitos T CD4-Positivos/patología , Linfopenia/inmunología , Linfopenia/microbiología , Sepsis/inmunología , Sepsis/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD20/análisis , Linfocitos B/química , Complejo CD3/análisis , Linfocitos T CD4-Positivos/química , Linfocitos T CD8-positivos/patología , Caspasa 9 , Caspasas/análisis , Caspasas/biosíntesis , Femenino , Citometría de Flujo , Humanos , Inmunohistoquímica , Inmunofenotipificación , Unidades de Cuidados Intensivos , Células Asesinas Naturales/patología , Recuento de Linfocitos , Linfopenia/mortalidad , Linfopenia/patología , Masculino , Persona de Mediana Edad , Sepsis/mortalidad , Bazo/enzimología , Bazo/patología , Coloración y EtiquetadoAsunto(s)
Marcadores Genéticos , Sepsis/genética , Animales , Modelos Animales de Enfermedad , Exones , Predisposición Genética a la Enfermedad , Humanos , Interleucina-1/genética , Linfotoxina-alfa/genética , Inhibidor 1 de Activador Plasminogénico/genética , Polimorfismo Genético , Pronóstico , Sepsis/mortalidad , Factor de Necrosis Tumoral alfa/genéticaAsunto(s)
Colon/lesiones , Enfermedades del Colon/diagnóstico , Hemorragia Gastrointestinal/diagnóstico , Hematoma/diagnóstico , Accidentes de Tránsito , Adulto , Enfermedades del Colon/diagnóstico por imagen , Enfermedades del Colon/patología , Diagnóstico Diferencial , Hemorragia Gastrointestinal/diagnóstico por imagen , Hemorragia Gastrointestinal/patología , Hemorragia Gastrointestinal/cirugía , Hematoma/diagnóstico por imagen , Hematoma/patología , Hematoma/cirugía , Humanos , Masculino , Tomografía Computarizada por Rayos XRESUMEN
Despite advances in supportive care, the morbidity and mortality rate resulting from sepsis and septic shock remain high (30 - 50%). A central hypothesis driving sepsis research in recent years is that this syndrome is the result of excessive inflammation. Therapies designed to inhibit the inflammatory response were first shown to be markedly beneficial in animal models of sepsis and then tested in numerous clinical trials involving thousands of patients. Three broad anti-inflammatory strategies have been investigated. First, glucocorticoids in high doses administered at the onset of sepsis were studied. This approach proved unsuccessful. More recently, however, glucocorticoids in lower doses have been found to have a beneficial effect in patients with septic shock. Whether the mechanism of this treatment benefit is through inhibition of inflammation, or by counteracting a relative steroid refractoriness occurring during sepsis, remains unknown. The next focus of research were agents active against the endotoxin molecule. However, as with the experience with glucocorticoids, this approach lacked a consistent pattern of efficacy. It is unclear if this lack of efficacy is the result of endotoxin being a poor therapeutic target, or from testing agents which lacked the appropriate biological activity. Most recently, clinical trials in sepsis have focused on inhibiting specific host pro-inflammatory mediators (e.g., TNF, interleukins). While individual trials of inhibitors of these pro-inflammatory mediators failed to show a convincing benefit, pooling the results of these trials suggest that this approach has a marginal effect, supporting a role for excessive inflammation in sepsis. An unanswered question is reconcilling the very favourable effects obtained with anti-inflammatory treatments in animal models with the marginal results in humans. Further clinical and laboratory research is needed and may provide insight into more effective ways to use the anti-inflammatory agents already tested, or to investigate other potentially more effective anti-inflammatory agents in this syndrome.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios/uso terapéutico , Sepsis/tratamiento farmacológico , Choque Séptico/tratamiento farmacológico , Animales , Anticuerpos/uso terapéutico , Endotoxinas/inmunología , Inhibidores Enzimáticos/uso terapéutico , Humanos , Óxido Nítrico Sintasa/antagonistas & inhibidores , Sepsis/patología , Choque Séptico/patología , EsteroidesRESUMEN
STUDY OBJECTIVES: Tracheostomy is one of the most commonly performed procedures in the patient receiving long-term mechanical ventilation. While percutaneous dilational tracheostomy (PDT) is becoming increasingly utilized as an alternative to conventional surgical tracheostomy, most literature evaluating these two techniques is neither prospective nor controlled. We performed a meta-analysis of available prospective controlled studies comparing PDT and surgical tracheostomy in critically ill patients to more fully understand the relative benefits and risks of these two procedures in this population. DESIGN: Meta-analysis using Mantel-Haenszel fixed effect model. INTERVENTIONS: We performed searches of MEDLINE, Current Contents, Best Evidence, Cochrane, and HealthSTAR databases from 1985 to present to identify prospective controlled studies comparing PDT and surgical tracheostomy in critically ill patients. After establishing clinical and statistical homogeneity (Q: statistic), studies were analyzed by a Mantel-Haenszel fixed effect model. For each clinical end point examined, PDT and surgical tracheostomy were compared by calculating either absolute differences or odds ratios (ORs) with 95% confidence intervals (CIs) for continuous or discrete variables, respectively. MEASUREMENTS AND RESULTS: We pooled data from five studies (236 patients) satisfying our search criteria to analyze eight clinical end points. Operative time was shorter for PDT than surgical tracheostomy: absolute difference with 95% CI, 9. 84 min (7.83 to 10.85 min). There was no difference comparing PDT and surgical tracheostomy with respect to overall operative complication rates: OR with 95% CI, 0.732 (0.05 to 9.37). However, relative to surgical tracheostomy, PDT was associated with less perioperative bleeding (OR with 95% CI, 0.14 [0.02 to 0.39]), a lower overall postoperative complication rate (OR with 95% CI, 0.14 [0.07 to 0.29]), as well as a lower postoperative incidence of bleeding (OR with 95% CI, 0.39 [0.17 to 0.88]), and stomal infection (OR with 95% CI, 0.02 [0.01 to 0.07]). No difference was identified in days intubated prior to tracheostomy (absolute difference with 95% CI, 0.16 days [- 0.9 to 1.22 days]), overall procedure-related complications (OR with 95% CI, 0.73 [0.06 to 9.37]), or death (OR with 95% CI, 0.63 [0.18 to 2.20]) comparing these two techniques. CONCLUSIONS: Despite its popularity, there are currently only a limited number of small studies prospectively evaluating PDT and surgical tracheostomy. Our meta-analysis of these studies suggests potential advantages of PDT relative to surgical tracheostomy, including ease of performance, and lower incidence of peristomal bleeding and postoperative infection. If confirmed by additional, adequately powered prospective trials, these findings support PDT as the procedure of choice for the establishment of elective tracheostomy in the appropriately selected critically ill patient.
Asunto(s)
Enfermedad Crítica , Traqueostomía/métodos , Pérdida de Sangre Quirúrgica , Intervalos de Confianza , Ensayos Clínicos Controlados como Asunto , Bases de Datos como Asunto , Dilatación , Humanos , Incidencia , Modelos Estadísticos , Oportunidad Relativa , Complicaciones Posoperatorias , Hemorragia Posoperatoria/etiología , Estudios Prospectivos , Respiración Artificial , Medición de Riesgo , Tasa de Supervivencia , Factores de Tiempo , Traqueostomía/efectos adversosRESUMEN
OBJECTIVE: Apoptosis is a cellular suicide program that can be activated by cell injury or stress. Although a number of laboratory studies have shown that ischemia/reperfusion injury can induce apoptosis, few clinical studies have been performed. The purpose of this study was to determine whether apoptosis is a major mechanism of cell death in intestinal epithelial cells and lymphocytes in patients who sustained trauma, shock, and ischemia/ reperfusion injury. DESIGN: Intestinal tissues were obtained intraoperatively from 10 patients with acute traumatic injuries as a result of motor vehicle collisions or gun shot wounds. A control population consisted of six patients who underwent elective bowel resections. Apoptosis was evaluated by conventional light microscopy, laser scanning confocal microscopy using the nuclear staining dye Hoechst 33342, immunohistochemical staining for active caspase-3, and immunohistochemical staining for cytokeratin 18. SETTING: Academic medical center. PATIENTS: Patients with trauma or elective bowel resections. MEASUREMENTS AND MAIN RESULTS: Extensive focal crypt epithelial and lymphocyte apoptosis were demonstrated by multiple methods of examination in the majority of trauma patients. Trauma patients having the highest injury severity score tended to have the most severe apoptosis. Repeat intestinal samples obtained from two of the trauma patients who had a high degree of apoptosis on initial evaluation were negative for apoptosis at the time of the second operation. Tissue lymphocyte apoptosis was associated with a markedly decreased circulating lymphocyte count in 9 of 10 trauma patients. CONCLUSIONS: Focal apoptosis of intestinal epithelial and lymphoid tissues occurs extremely rapidly after injury. Apoptotic loss of intestinal epithelial cells may compromise bowel wall integrity and be a mechanism for bacterial or endotoxin translocation into the systemic circulation. Apoptosis of lymphocytes may impair immunologic defenses and predispose to infection.
Asunto(s)
Apoptosis/fisiología , Muerte Celular/fisiología , Células Epiteliales/patología , Mucosa Intestinal/patología , Linfocitos/patología , Traumatismo Múltiple/patología , Choque/patología , Adolescente , Adulto , Caspasa 3 , Caspasas/metabolismo , Femenino , Humanos , Mucosa Intestinal/irrigación sanguínea , Isquemia/patología , Queratinas/metabolismo , Masculino , Persona de Mediana Edad , Daño por Reperfusión/patologíaRESUMEN
BACKGROUND: Warfarin use is complicated by an erratic dose response. Interpatient variability associated with warfarin therapy may be partly attributable to polymorphisms of the cytochrome P450 (CYP) complex. The purpose of this study was to ascertain the frequency and influence of CYP polymorphisms on warfarin dosing in our patient population. METHODS: Patients receiving warfarin therapy were recruited from the inpatient divisions of our hospital. Genotyping for known polymorphic alleles of the CYP subfamilies CYP2C9 (CYP2C9*1, CYP2C9*2, and CYP2C9*3) and CYP2A6 (CYP2A6*1, CYP2A6*2) with the use of standard methods of polymerase chain reaction amplification was performed. An unpaired t test was used to statistically compare genotypes. RESULTS: Genotype frequency in 38 patients is as follows: CYP2C9*1/CYP2C9*1, 71%; CYP2C9*1/CYP2C9*2, 21%; CYP2C9*2/CYP2C9*2, 3%; CYP2C9*1/CYP2C9*3, 5%; CYP2A6*1/CYP2A6*1, 95%; CYP2A6*1/CYP2A6*2, 5%. Compared to a wild-type genotype, the presence of the CYP2C9*2, CYP2C9*3, or CYP2A6*2 allele was associated with a significant reduction in weekly warfarin dose (mean weekly warfarin dose [+/- SE] for wild-type genotype was 0.397 +/- 0.024 mg/kg/wk vs 0.307 +/- 0.03 mg/kg/wk for carriers of CYP2C9*2, CYP2C9*3, or CYP2A6*2 polymorphism; P =.03). CONCLUSIONS: Polymorphisms that impair warfarin metabolism are common, occurring in 34% of patients, and are associated with increased warfarin sensitivity. The use of genotypic information to prescribe more accurate doses of warfarin may increase the safety and efficacy of this medication.
Asunto(s)
Anticoagulantes/uso terapéutico , Sistema Enzimático del Citocromo P-450/genética , Polimorfismo Genético , Warfarina/uso terapéutico , Anticoagulantes/administración & dosificación , Población Negra , Relación Dosis-Respuesta a Droga , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Missouri , Mutación Puntual , Mapeo Restrictivo , Warfarina/administración & dosificación , Población BlancaRESUMEN
OBJECTIVE: The lymphocyte is a principal mediator of the inflammatory response, and lymphocyte depletion via apoptosis may be an important mechanism of modulating inflammation. Increased oxygen consumption occurs during sepsis and results in the generation of reactive oxygen species. Although reactive oxygen species initiate apoptosis in many biological systems, their role in controlling lymphocyte apoptosis during sepsis is unclear. The objective of this study was to better characterize the role of oxidative stress in precipitating lymphocyte apoptosis during sepsis and to specifically define the role of the CuZn superoxide dismutase (SOD) enzyme complex, a major antioxidant defense, in modulating this process. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory at an academic medical center. SUBJECTS: Mice that were either genetically normal or that were deficient in or overexpressed the enzyme CuZn SOD. INTERVENTIONS: Mice from each genetic group were randomized to no manipulation (control), sham surgery, or cecal ligation and puncture. Mice were killed 18-24 hrs after study entry, and the thymi and spleen were removed for analysis of apoptosis. MEASUREMENTS AND MAIN RESULTS: Lymphocyte apoptosis was assessed by three independent methods: light microscopy, fluorescent terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling, and DNA gel electrophoresis. Comparisons were performed using standard parametric statistical tests. Lymphocyte apoptosis was present in mice after CLP but not in control mice or in mice after sham surgery (p < .05). Mice completely lacking CuZn SOD developed significantly more lymphocyte apoptosis than did either partially CuZn SOD-deficient or genetically normal mice (p < .05). This apoptosis was more pronounced in the thymus than the spleen and, within the thymus, more prominent in the cortex than medulla (p < .05 for all). In contrast, mice that overexpressed CuZn SOD did not differ in the amount of apoptosis after CLP compared with genetically normal mice (p = NS for all). CONCLUSIONS: Oxidative stress occurs in sepsis and appears to be one stimulus for the development of lymphocyte apoptosis, a process that is partly regulated by CuZn SOD. However, we were unable to demonstrate that overexpression of this enzyme suppressed lymphocyte apoptosis, suggesting that either other antioxidant defenses or other pathways independent of oxidative stress may mediate lymphocyte elimination in this syndrome.