Biomedical subjects

C R Smith

Publications and source records attributed to C R Smith.

At least 109 records · Page 6Linked to original sources

PubMed1995

Vesamicol analogues as sigma ligands. Molecular determinants of selectivity at the vesamicol receptor.

The present study compares the affinities of 2-(4-phenylpiperidino)cyclohexanol (vesamicol, 1) and selected analogues of the latter at the vesamicol receptor (VR) with the corresponding affinities at sigma 1 and sigma 2 binding sites. For this study, the parent structure 1 was divided into three fragments: A (cyclohexyl), B (piperidyl) and C (phenyl). Vesamicol analogues were then selected to reflect structural modifications in these fragments. Consistent with earlier reports, vesamicol was found to exhibit nanomolar affinities at the VR and sigma 1 and sigma 2 sites, resulting in poor selectivity for the VR over the sigma sites. Vesamicol analogues characterized by an acyclic A-fragment showed moderate to low affinities at the VR and moderate to high affinities at sigma 1 and sigma 2 sites. As a result, many of these analogues showed poor selectivity for the VR. Replacement of the C4 carbon of 1 with a halobenzyl amine resulted in higher affinities at the VR coupled with moderate to low affinities at sigma 1 and sigma 2 sites. The introduction of a benzofused substituent at the C4 and C5 positions of 1 (compound 2) resulted in a 200-fold increase in affinity at the VR accompanied by a 5- to 6-fold decrease in affinity at sigma 1 and sigma 2 sites relative to the parent structure. Consequently, compound 2 showed 12,000-fold higher affinity at the VR than at sigma sites. Restricting the rotation of fragment C relative to B (by means of alkyl and alkenyl bridges) generally yielded analogues with subnanomolar affinities at the VR. The corresponding affinities of these spirofused conformationally restricted analogues were moderate to poor at sigma 1 and sigma 2 sites when fragment A was preserved. In contrast, the affinities at sigma 1 and sigma 2 sites were decreased 3- to 11-fold when fragment A was modified at position C4 and decreased up to 100-fold with benzofusion at the C4 and C5 positions of fragment A. Consequently, the spirofused analogues 15-19 were among the most selective VR ligands examined. Thus, the effect of conformational restriction in fragments A and B-C is to increase affinity at the VR while decreasing affinity at sigma 1 and sigma 2 sites, and thereby increasing selectivity for the VR over the sigma sites.

Animals↗

PubMed1995

Classmode: a new data format for real-time multiparameter data analysis and data compression.

A new data acquisition and analysis format (classmode) was developed that allows real-time data classification in a flow cytometer. In our cytometer, detected events were classified in real time by their presence or absence in a set of look-up tables (LUT). A modification of the cytometer hardware allows the exclusive transfer of the LUT data to the acquisition/storage computer. Using a combination of 8 LUTs, the analyzed events can be classified into 256 subpopulations. Real-time data classification results in an increased data transfer rate and a significant compression of the data.

Cells, Cultured↗

PubMed1995

Blockade of the human platelet GPIIb/IIIa receptor by a murine monoclonal antibody Fab fragment (7E3): potent dose-dependent inhibition of platelet function.

The platelet glycoprotein (GP) IIb/IIIa receptor can bind fibrinogen, von Willebrand factor, and other adhesive ligands; this binding is the final common pathway mediating platelet aggregation. The purpose of this study was to evaluate the safety and platelet inhibitory characteristics of the Fab fragment of the murine monoclonal anti-GPII/IIIa 7E3 antibody (m7E3 Fab) when administered intravenously as a single bolus dose, as a single and repeat bolus dose, and as a single bolus dose followed by continuous infusions of varying duration. Various dosage regimens of m7E3 Fab were studied in 74 patients with stable angina. Dosage regimens included single doses of m7E3 Fab from 0.1 to 0.3 mg/kg, a single dose of 0.20-0.30 mg/kg, and a repeat dose of 0.05 mg/kg, or a loading dose followed by a continuous infusion of m7E3 Fab for up to 36 hours. To assess the effect of m7E3 Fab on platelet function, quantitative blockade of GPIIb/IIIa receptors, inhibition of ex vivo platelet aggregation, and template bleeding time were measured in all patients. Dose-dependent inhibition of platelet function was evident in response to escalating bolus doses of m7E3 Fab, with maximum inhibition observed at 0.25-0.30 mg/kg body weight; at the 0.30 mg/kg dose, mean (+/- SE) GPIIb/IIIa receptor blockade was 81 +/- 3%, ex vivo platelet aggregation in response to 20 microM ADP was 14 +/- 6% of baseline, and the median bleeding time was > 20 minutes. Although platelet function gradually recovered following a single bolus injection, platelet inhibition could be sustained by continuous, low-dose infusion of the antibody. Platelet inhibition occurred within minutes, but m7E3 Fab that did not bind to platelets cleared rapidly from circulation. Sixteen percent of the m7E3 Fab-injected subjects exhibited low titer, human anti-murine antibody responses. No significant bleeding or allergic reactions were observed in any patients. One of the 74 patients developed transient thrombocytopenia soon after receiving m7E3 Fab. These studies establish that m7E3 Fab can be administered safely at doses that cause profound inhibition of platelet function.

Adult↗

PubMed1995

Rapid optimization of electroporation conditions for plant cells, protoplasts, and pollen.

The optimization of electroporation conditions for maximal uptake of DNA during direct gene transfer experiments is critical to achieve high levels of gene expression in transformed plant cells. Two stains, trypan blue and fluorescein diacetate, have been applied to optimize electroporation conditions for three plant cell types, using different square wave and exponential wave electroporation devices. The different cell types included protoplasts from tobacco, a stable mixotrophic suspension cell culture from soybean with intact cell walls, and germinating pollen from alfalfa and tobacco. Successful electroporation of each of these cell types was obtained, even in the presence of an intact cell wall when conditions were optimized for the electroporation pulse. The optimal field strength for each of these cells differs, protoplasts having the lowest optimal pulse field strength, followed by suspension cells and finally germinating pollen requiring the strongest electroporation pulse. A rapid procedure is described for optimizing electroporation parameters using different types of cells from different plant sources.

Electroporation↗

PubMed1995

Use of aprotinin in LVAD recipients reduces blood loss, blood use, and perioperative mortality.

Aprotinin, a bovine protease inhibitor, has been used extensively in patients undergoing cardiac surgical procedures in an effort to minimize blood loss and prevent the complications associated with blood replacement. We sought to evaluate the effect of aprotinin on postoperative blood loss, renal function, and the incidence of right ventricular failure in patients undergoing placement of a TCI Heartmate left ventricular assist device as a bridge to cardiac transplantation. Retrospective data analysis in 142 patients (42 receiving aprotinin and 100 untreated) demonstrated that the use of aprotinin was associated with a significant decrease in postoperative blood loss (p = 0.019) and in the intraoperative packed red blood cell transfusion (p = 0.019) and total blood product (p = 0.016) requirements. A transient, yet significant, increase in the postoperative creatinine level in the aprotinin group (p = 0.0006), but not in blood urea nitrogen level (p = 0.22), was noted. Interestingly, we noted an association between blood loss and the subsequent development of right ventricular failure; patients who required a right ventricular assist device bled significantly more than did those who did not suffer right ventricular failure (p = 0.02). Additionally, aprotinin recipients benefited by a reduction of nearly one half in the incidence of the need for a right ventricular assist device. The incidence of perioperative mortality was reduced in those receiving aprotinin compared with that in untreated patients, (p = 0.05). We conclude that aprotinin is safe and effective in decreasing postoperative blood loss and intraoperative blood product requirements, and in reducing perioperative mortality in patients undergoing left ventricular assist device placement as a bridge to cardiac transplantation.

Adult↗

PubMed1995

Cerebral dysfunction after cardiac operations in elderly patients.

BACKGROUND: Cerebral injury remains a significant complication of cardiac operations. We determined the incidence of cerebral dysfunction in a population of elderly patients undergoing open chamber cardiac operations (group 1) as compared with a younger population (group 2) and an age-matched group of elderly patients undergoing major noncardiac operations (group 3). METHODS: Sixty-eight patients (55 for open chamber cardiac operations and 13 for noncardiac operations) were prospectively studied. Patients were evaluated preoperatively and postoperatively before hospital discharge using a complete neurologic examination and a battery of standard neuropsychometric tests, and at surgical follow-up with neuropsychometric tests only. RESULTS: Postoperative changes detected by neurologic examination consisted of the appearance of new primitive reflexes in all groups. No statistically significant differences in incidence were found. The neuropsychometric performance of group 1 patients was statistically different from that of patients in groups 2 and 3 only in the early follow-up period. CONCLUSIONS: Elderly patients having open chamber cardiac operations exhibit significantly more cerebral dysfunction in the early postoperative period than those undergoing major noncardiac operations and younger patients after open chamber procedures. These changes do not persist into the late follow-up period.

Age Factors↗

PubMed1995

Ibogaine possesses a selective affinity for sigma 2 receptors.

The alkaloid ibogaine is potentially useful to reduce craving for several drugs of abuse, but its mechanism of action is not known. In the current study, in vitro studies were conducted in order to determine the affinity of ibogaine for sigma receptors. Our results indicate that ibogaine has a relatively high affinity for sigma 2 receptors (Ki = 90.4 and 250 nM) and a significantly lower affinity for sigma 1 receptors (Ki = 9310 nM). These data suggest that ibogaine may have a higher affinity at sigma 2 receptors than any other known CNS receptor. Its low affinity for sigma 1 receptors also suggests that ibogaine may be a suitable lead compound for structure-activity relationship studies aimed at developing sigma 2-selective ligands.

Animals↗

PubMed1995

Heart transplantation in children with congenital heart disease.

OBJECTIVES: The aim of this study was to describe heart transplantation in children with congenital heart disease and to compare the results with those in children undergoing transplantation for other cardiac diseases. BACKGROUND: Reports describe decreased survival after heart transplantation in children with congenital heart disease compared with those with cardiomyopathy. However, transplantation is increasingly being considered in the surgical management of children with complex congenital heart disease. Present-day results from this group require reassessment. METHODS: The diagnoses, previous operations and indications for transplantation were characterized in children with congenital heart disease. Pretransplant course, graft ischemia time, post-transplant survival and outcome (rejection frequency, infection rate, length of hospital stay) were compared with those in children undergoing transplantation for other reasons (n = 47). RESULTS: Thirty-seven children (mean [+/- SD] age 9 +/- 6 years) with congenital heart disease underwent transplantation; 86% had undergone one or more previous operations. Repair of extracardiac defects at transplantation was necessary in 23 patients. Causes of death after transplantation were donor failure in two patients, surgical bleeding in two, pulmonary hemorrhage in one, infection in four, rejection in three and graft atherosclerosis in one. No difference in 1- and 5-year survival rates (70% vs. 77% and 64% vs. 65%, respectively), rejection frequency or length of hospital stay was seen between children with and without congenital heart disease. Cardiopulmonary bypass and donor ischemia time were significantly longer in patients with congenital heart disease. Serious infections were more common in children with than without congenital heart disease (13 of 37 vs. 6 of 47, respectively, p = 0.01). CONCLUSIONS: Despite the more complex cardiac surgery required at implantation and longer donor ischemic time, heart transplantation can be performed in children with complex congenital heart disease with success similar to that in patients with other cardiac diseases.

Adolescent↗

PubMed1995

Single-stage treatment of sternal wound complications in heart transplant recipients in whom pectoralis major myocutaneous advancement flaps were used.

Treatment of sternal wound complications is controversial, particularly in immunosuppressed heart transplant recipients. Regardless of the severity of infection, we combine immediate, aggressive débridement with bilateral pectoralis major myocutaneous advancement flaps in a single procedure. Compared with management with pectoralis major turnover flaps or distant pedicled muscle flaps, treatment of these sternal wounds with pectoralis major myocutaneous advancement flaps is simpler and quicker and provides better aesthetic results. Furthermore, because pectoralis major myocutaneous flaps are based on the thoracoacromial arteries, whether or not the internal mammary arteries have previously been harvested for coronary grafts is irrelevant. Twenty consecutive heart transplant recipients with sternal wound complications were treated with this technique. No intraoperative or perioperative deaths occurred. The morbidity rate was 30%, with seroma treated by needle aspiration in four patients (20%) being the most common complication. Only one patient had a postoperative wound infection. All patients had excellent functional and aesthetic results.

Debridement↗

PubMed1995

Safety and efficacy of aprotinin under conditions of deep hypothermia and circulatory arrest.

Aprotinin has been successfully used to reduce blood loss and blood product requirements in patients undergoing primary and reoperative cardiac operations. Its safety and efficacy during profound hypothermia and circulatory arrest have been questioned, however. A retrospective review compared 24 patients who received aprotinin during complex aortic procedures under profound hypothermia and circulatory arrest with 24 age-matched patients undergoing similar procedures without aprotinin. Activated clotting time was maintained at longer than 500 seconds (kaolin activating agent) or longer than 750 seconds (celite). We observed no statistically significant difference in the incidence of neurologic events (p not significant) or myocardial infarctions (p not significant), and there was a trend toward reduced in-hospital mortality rate in aprotinin-treated patients. A higher incidence of postoperative renal dysfunction was encountered in aprotinin-treated patients. Aprotinin recipients had a significant reduction in requirements for postoperative homologous erythrocytes (p = 0.01). We conclude that aprotinin may be safely and effectively used in patients undergoing deep hypothermia and circulatory arrest.

Aortic Dissection↗

PubMed1995

Inhaled nitric oxide fails to confer the pulmonary protection provided by distal stimulation of the nitric oxide pathway at the level of cyclic guanosine monophosphate.

It has been suggested that inhaled nitric oxide gas may be beneficial after lung transplantation, because endogenous levels of pulmonary nitric oxide decline rapidly after reperfusion. However theoretical concerns remain about the formation of highly toxic oxidants during the quenching of nitric oxide by superoxide. To determine whether distal stimulation of the nitric oxide-cyclic guanosine monophosphate pathway at the level of cyclic guanosine monophosphate might confer the beneficial vascular effects of nitric oxide without its potential toxicities, we studied an orthotopic rat left lung transplant model. In this model, hemodynamic and survival measurements can be obtained independent of the native right lung. Lungs were preserved for 6 hours at 4 degrees C in Euro-Collins solution alone (control, n = 6) or supplemented with the cyclic guanosine monophosphate analog, 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic guanosine monophosphate (cGMP, n = 4). In additional experiments in which lungs were preserved with Euro-Collins solution alone, inhaled nitric oxide was administered during reperfusion (NO, n = 12). Thirty minutes after transplantation and ligation of the native right pulmonary artery, pulmonary vascular resistance, arterial oxygenation, graft neutrophil infiltration (myeloperoxidase activity), and recipient survival were evaluated. Cyclic guanosine monophosphate decreased pulmonary vascular resistance (1.1 +/- 0.2 vs 12.1 +/- 6.3 mm Hg/ml/min, p < 0.05), improved oxygen tension (369 +/- 56 vs 82.8 +/- 48 mm Hg, p < 0.05), reduced myeloperoxidase activity (1.7 +/- 0.3 vs 3.1 +/- 0.9 delta Abs 460 nm/min, p < 0.05), and improved recipient survival (100% vs 0%, p < 0.005) compared with Euro-Collins solution alone (control group). Animals receiving inhaled nitric oxide during reperfusion did not differ from control animals with respect to any of these parameters. These data suggest that distal stimulation of the nitric oxide-cyclic guanosine monophosphate pathway at the level of cyclic guanosine monophosphate has a protective effect that is not seen with inhaled nitric oxide in the immediate pulmonary reperfusion period.

Administration, Inhalation↗

PubMed1995

Nitroglycerin maintains graft vascular homeostasis and enhances preservation in an orthotopic rat lung transplant model.

Transplanted lungs often fail during the peritransplantation period for poorly understood reasons. Because the nitric oxide pathway regulates pulmonary vascular tone, helps to maintain the integrity of the endothelial barrier, and modulates neutrophil adhesivity and activation, we hypothesized that perturbation of this pathway during the preservation and reperfusion of transplanted lungs might play a critical role in mediating early graft failure. To evaluate whether supplementing the preservation solution with the nitric oxide donor nitroglycerin enhances lung preservation for transplantation, we obtained hemodynamic measurements in a model of orthotopic left lung transplantation in the rat after ligation of the native right pulmonary artery. In these experiments, recipient survival and hemodynamics depended solely on the transplanted lung. The left lung was harvested from 22 rats, flushed with either lactated Ringer's solution alone (control, n = 11) or Ringer's solution supplemented with nitroglycerin (0.1 mg/ml, n = 11), preserved for 4 hours at 4 degrees C, and then transplanted using a rapid cuff technique for bronchial and vascular anastomoses. Nitroglycerin significantly improved arterial blood oxygenation (339 +/- 66 versus 130 +/- 12 mm Hg, p < 0.05), increased pulmonary arterial flow (7.6 +/- 1.9 versus 0.9 +/- 0.2 ml/min, p < 0.005), decreased pulmonary vascular resistance (1.7 +/- 0.4 versus 6.6 +/- 1.9 x 10(3) Wood units, p < 0.05), and enhanced recipient survival (64% versus 0%, p < 0.05). Control grafts had significantly greater neutrophil accumulation (50% greater as quantified by myeloperoxidase activity, p < 0.05) than grafts preserved in the presence of nitroglycerin. These studies show that supplementation of the preservation solution with the nitric oxide donor nitroglycerin maintains graft vascular homeostasis and significantly improves pulmonary function and recipient survival after transplantation.

Animals↗

PubMed1995

The effects of self-hypnosis on quality of life following coronary artery bypass surgery: preliminary results of a prospective, randomized trial.

The effects of complementary techniques and alternative medicine on allopathic therapies is generating much interest and research. To properly evaluate these techniques, well controlled studies are needed to corroborate the findings espoused by individuals practicing complementary medicine therapies. To this end, we evaluated the role of one of these therapies, self-hypnosis relaxation techniques, in a prospective, randomized trial to study its effects on quality of life after coronary artery bypass surgery. Subjects were randomized to a control group or a study group. Study group patients were taught self-hypnosis relaxation techniques the night prior to surgery. The control group received no such treatment. Patients then underwent routine cardiac management and care. The main endpoint of our study was quality of life, assessed by the Profile of Moods Scale. Results demonstrated that patients undergoing self-hypnosis the night prior to coronary artery bypass surgery were significantly more relaxed than the control group (p = 0.0317). Trends toward improvement were also noted in depression, anger, and fatigue. This study demonstrates the beneficial effects of self-hypnosis relaxation techniques on coronary surgery. This study also identifies endpoints and a study design that can be used to assess complementary medicine therapies. Results of this preliminary investigation are encouraging and demonstrate a need for further well-controlled studies.

Affect↗

PubMed1995

Development of a clinically applicable high-speed flow cytometer for the isolation of transplantable human hematopoietic stem cells.

A high-speed cell sorter capable of a throughput speed 4-5-fold greater than commercially available systems was developed and evaluated as a processing tool for isolating purified hematopoietic stem cell grafts. The clinical high-speed sorter (CHSS) serves as a single-pass, multiparameter processing tool that provides the means to isolate a highly purified population of cells from starting cell populations with extremely low frequencies. The sorter incorporates environmental barriers to create a sterile environment for cell processing. Monoclonal antibodies and reagents produced under good manufacturing practices (GMP) are used to isolate hematopoietic stem cells by means of the CHSS. Using this technology, the CD34+Thy-1+Lin- hematopoietic stem cell population has been isolated from normal adult bone marrow and mobilized peripheral blood. The sorted cells have been shown to be sterile and viable and to retain hematopoietic function.

Cell Separation↗

PubMed1995

Do standard monitoring sites reflect true brain temperature when profound hypothermia is rapidly induced and reversed?

BACKGROUND: Brain temperature is closely approximated by most body temperature measurements under normal anesthetic conditions. However, when thermal autoregulation is overridden, large temperature gradients may prevail. This study sought to determine which of the standard temperature monitoring sites best approximates brain temperature when deep hypothermia is rapidly induced and reversed during cardiopulmonary bypass. METHODS: Twenty-seven patients underwent cardiopulmonary bypass and deep hypothermic circulatory arrest in order for each to have a giant cerebral aneurysm surgically clipped. Brain temperatures were measured directly with a thermocouple embedded in the cerebral cortex. Eight other body temperatures were monitored simultaneously with less invasive sensors at standard sites. RESULTS: Brain temperature decreased from 32.6 +/- 1.4 degrees C (mean +/- SD) to 16.7 +/- 1.7 degrees C in 28 +/- 7 min, for an average cerebral cooling rate of 0.59 +/- 0.15 degrees C/min. Circulatory arrest lasted 24 +/- 15 min and was followed by 63 +/- 17 min of rewarming at 0.31 +/- 0.09 degrees C/min. None of the monitored sites tracked cerebral temperature well throughout the entire hypothermic period. During rapid temperature change, nasopharyngeal, esophageal, and pulmonary artery temperatures corresponded to brain temperature with smaller mean differences than did those of the tympanic membrane, bladder, rectum, axilla, and sole of the foot. At circulatory arrest, nasopharyngeal, esophageal, and pulmonary artery mean temperatures were within 1 degree C of brain temperature, even though individual patients frequently exhibited disparate values at those sites. CONCLUSIONS: When profound hypothermia is rapidly induced and reversed, temperature measurements made at standard monitoring sites may not reflect cerebral temperature. Measurements from the nasopharynx, esophagus, and pulmonary artery tend to match brain temperature best but only with an array of data can one feel comfortable disregarding discordant readings.

Adult↗

PubMed1995

Metabolic and hemodynamic responses to walking with shoulder-worn exercise weights: a brief report.

This study examined the acute physiological responses to steady-rate walking with additional weight carried at shoulder level. Sixteen healthy subjects completed two treadmill walking bouts with and without a 4.54-kg shoulder-worn load carriage system in place. Addition of the external shoulder weights resulted in small increases in level walking oxygen uptake (+0.44 ml.kg-1.min-1; +0.03 L.min-1) and minute ventilation volumes (+0.81 L.min-1) (p < 0.05). RER values, heart rate (+3 beats.min-1), and blood pressure responses [systolic blood pressure (SBP) + 4.5 mm Hg, diastolic blood pressure (DBP) + 1.3 mm Hg] were not significantly changed (p > 0.05). These findings indicate that the efficacy of shoulder-worn exercise weights to augment the physiological demand of walking exercise is marginal at best.

Adolescent↗

PubMed1995

Management strategies for pulmonary vein thrombosis following single lung transplantation.

Pulmonary vein thrombosis following lung transplantation is an infrequently reported and often fatal vascular complication. Two cases of early pulmonary vein thrombosis following single lung transplantation are described. Both patients underwent surgical thrombectomy and anastomotic reconstruction following institution of cardiopulmonary bypass, but died of multiorgan failure within 5 days of diagnosis. The efficacy of transesophageal echocardiography as a diagnostic modality, as well as medical and surgical management strategies for thrombectomy, are discussed.

Adult↗

PubMed1994

Treatment of septic shock with human monoclonal antibody HA-1A. A randomized, double-blind, placebo-controlled trial. CHESS Trial Study Group.

OBJECTIVE: To compare the effectiveness of 100 mg of HA-1A and placebo in reducing the 14-day all-cause mortality rate in patients with septic shock and gram-negative bacteremia in the Centocor: HA-1A Efficacy in Septic Shock (CHESS) trial, and to assess the safety of 100 mg of HA-1A given to patients with septic shock who did not have gram-negative bacteremia. DESIGN: Large, simple, group-sequential, randomized, double-blind, multicenter, placebo-controlled trial. SETTING: 603 investigators at 513 community and university-affiliated hospitals in the United States. PATIENTS: Within 6 hours before enrollment, the patients had been in shock with a systolic blood pressure of less than 90 mm Hg after adequate fluid challenge or had received vasopressors to maintain blood pressure. These episodes of shock began within 24 hours of enrollment. A presumptive clinical diagnosis of gram-negative infection as the cause of the shock episode and a commitment from the patients' physicians to provide full supportive care were required. MEASUREMENTS: Blood cultures were obtained within 48 hours of enrollment, and death at day 14 after treatment was recorded. Adverse events occurring within 14 days after enrollment were also tabulated. RESULTS: 2199 patients were enrolled; 621 (28.2%) met all enrollment criteria, received HA-1A or placebo, and had confirmed gram-negative bacteremia. Mortality rates in this group were as follows: placebo, 32% (95 and HA-1A, 33% (109 of 328) (P = 0.864, Fisher exact test, two-tailed; 95% CI for the difference, -6.2% to 8.6%). Mortality rates in the patients without gram-negative bacteremia were as follows: placebo, 37% (292 of 793) and HA-1A, 41% (318 of 785) (P = 0.073, Fisher exact test, one-tailed; CI, -0.8% to 8.8%). CONCLUSIONS: In this trial, HA-1A was not effective in reducing the 14-day mortality rate in patients with gram-negative bacteremia and septic shock. These data do not support using septic shock as an indication for HA-1A treatment. If HA-1A is effective in reducing the mortality rate in patients dying from endotoxemia, these patients must be identified using other treatment criteria.

Adult↗