Search PubMed⌕ Search

Biomedical subjects

B J Nelson

Publications and source records attributed to B J Nelson.

At least 19 recordsLinked to original sources
PubMed1999

Bactericidal/permeability-increasing protein (rBPI21) in patients with hemorrhage due to trauma: results of a multicenter phase II clinical trial. rBPI21 Acute Hemorrhagic Trauma Study Group.

BACKGROUND: Infection and organ failure are the most common causes of death or serious complication in trauma patients surviving initial resuscitation and operation. Of the many possible causes of these complications, bacterial translocation and release of harmful cytokines and oxygen free radicals may play an important role in the pathogenesis of the complications associated with traumatic hemorrhage. Recombinant human bactericidal/permeability-increasing protein (rBPI21) has antibacterial and antiendotoxin properties, reduces cytokine levels, and increases survival in animal models of hemorrhagic shock. The primary objective of this study was to evaluate the safety and efficacy of prophylactic rBPI21 infusion in patients with hemorrhage due to trauma. METHODS: This was a phase II, multicenter, randomized, double-blind, placebo-controlled trial. Patients who required at least 2 U of blood were randomized to receive rBPI21 (4 mg x kg(-1) x d(-1) for 2 consecutive days) or an equivalent volume of placebo by continuous infusion within 12 hours of injury. The primary efficacy end point was mortality or serious complication occurring during the first 15 days of the study. Safety was monitored clinically and by laboratory panels during the study period. RESULTS: A total of 401 patients were treated (202 in the rBPI21 group and 199 in the placebo group). The composite end point rate of mortality or serious complication through day 15 was 46% in the placebo group and 39% in the rBPI21 group (hazard ratio = 0.79; p = 0.13). Secondary analysis, which adjusted for age, mechanism of injury, Injury Severity Score (1990 version), and units of blood received before study drug infusion showed similar results (hazard ratio = 0.79; p = 0.14). The proportion of patients who developed at least one serious organ dysfunction was 22% in the placebo group and 16% in the rBPI21 group (hazard ratio = 0.71; p = 0.14). The proportion of patients who developed either pneumonia or acute respiratory distress syndrome was 32% in the placebo group and 22% in the rBPI21 group (hazard ratio = 0.66; post hocp = 0.03). The beneficial trends of rBPI21 were observed in both blunt and penetrating trauma and were generally observed across different age groups, Injury Severity Scores, and units of blood transfused. No treatment difference was observed in mortality or resource utilization in this phase II study. CONCLUSION: rBPI21 was well-tolerated and demonstrated a favorable trend in reducing the composite primary end point of mortality or serious complication through day 15, especially respiratory complications, in patients with hemorrhage due to trauma. A phase III study is currently in progress.

Adolescent↗
PubMed1998

A run in the sun.

Explore the source record for details and available documents.

Health Promotion↗
PubMed1998

In vitro tooth whitening by a sodium bicarbonate/peroxide dentifrice.

The main purpose of this laboratory study was to determine the tooth whitening effect of a baking soda dentifrice containing stabilized 1% hydrogen peroxide following repeated applications to intrinsically stained teeth. Additional objectives were to investigate (1) the influence of tooth surface curvature and moisture on color measurements, (2) preliminary treatment parameters using 1% hydrogen peroxide solution, and (3) the relationship between Vita shade guide standards and instrumental color readings. Human tooth specimens with intrinsic stain were specially prepared and measured for color (L*a*b*) by means of diffuse reflectance spectrophotometry. Specimens were measured under wet and dry conditions with natural and flattened enamel surfaces. A preliminary test was conducted with 1% H2O2 solution to establish tooth whitening versus treatment time. Then, new tooth specimens were treated repeatedly with slurries of silica, baking soda, or baking soda/peroxide dentifrices at 30-minute intervals, and color measurements were taken under both wet and dry conditions after 4, 8, 16 and 24 hours. L*a*b* color measurements of the Vita shade guide teeth were also made in order to relate laboratory color changes to clinical effects. The parameter testing results showed that flattening the enamel surface had no effect on tooth color, but the teeth rapidly became lighter and less yellow upon air-drying. The 1% H2O2 solution caused both a significant decrease in yellow (b*) and an increase in lightness (L*). Since the reduction for b* occurred more rapidly and to a greater extent than the L* factor, the b* component may be the more important indicator of tooth whitening by bleaching. Compared to the silica and baking soda dentifrices, the baking soda/peroxide dentifrice significantly decreased the yellow color (b*) of the teeth after 8 or more hours of topical treatment. The instrumental color readings of the Vita Shade guide teeth showed that the color differences between the standards were not linear or consistent, and their accuracy for assessing clinical changes in tooth whiteness is questionable.

Color↗
PubMed1997

Preliminary evaluation of recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in children with severe meningococcal sepsis.

BACKGROUND: Meningococcal sepsis remains an important cause of morbidity and mortality. We hypothesised that children with severe meningococcaemia might benefit from inhibition of the inflammatory processes thought responsible for fulminant disease. rBPI21 is a recombinant, N-terminal fragment of human bactericidal/permeability-increasing protein, which kills meningococci and binds to and clears bacterial endotoxin, these being the primary inducers of the systemic inflammation. The aim of this study was to determine the safety and kinetics of rBPI21 in children with severe meningococcaemia and to make a preliminary assessment of clinical outcome. METHODS: In this open-label, dose-escalation, phase I/II trial in severe meningococcaemia (Glasgow meningococcal prognostic septicaemia score [GMSPS] > or = 8), 26 patients aged 1-18 years, who had received their first dose of antibiotics no more than 8 hours earlier were given rBPI21 by infusion at total doses of 1.0, 2.0, and 4.0 mg/kg. FINDINGS: The patients had significantly raised plasma concentrations of bacterial endotoxin and cytokines. Peak and steady state BPI concentrations were comparable with pharmacokinetic data in healthy adults. All complications were compatible with the expected pattern for severe meningococcal sepsis. Only one patient died. This outcome was found to compare favourably with a predicted mortality of > or = 30% by GMSPS, > or = 15% by plasma endotoxin values, > or = 28% by plasma interleukin-6 concentrations, 29-49% by severity of coagulopathy, and 20% (11/54) by comparison with recent historical patients consecutively treated in participating centres before this study. INTERPRETATION: This, the first clinical trial or rBPI21, shows that rBPI21 can be safely administered to children with severe meningococcaemia and that the pharmacokinetics are consistent with patterns seen in healthy adults. Predicted mortality, on the basis of GMSPS, laboratory indices of inflammation and coagulopathy, and historical controls, was for between four and eight deaths. These findings have prompted a phase III randomised trial.

Adult↗
PubMed1996

Functional outcome of thoracolumbar burst fractures managed with hyperextension casting or bracing and early mobilization.

STUDY DESIGN: A retrospective study to review the results of unstable thoracolumbar burst fractures managed with casting or bracing and early ambulation in neurologically healthy patients. OBJECTIVES: To determine the clinical outcome of patients with unstable burst fractures of the thoracolumbar spine treated without surgery, and to identify any variables that may adversely influence the final outcome. SUMMARY OF BACKGROUND DATA: The management of unstable fractures of the thoracolumbar spine as described by Bedbrook involves a period of recumbency for 6-8 weeks followed by gradual mobilization. Newer techniques of surgical stabilization of the fracture and decompression of the neural elements have become popular because immediate stability of the spine is created and because the need for prolonged bedrest and hospitalization is eliminated. There have been only three reports in the literature describing the nonoperative management of these fractures with early mobilization; some authors believe that this is appropriate only if the posterior column is intact. The results reported in the literature of nonoperative management of thoracolumbar burst fractures have indicated that this is an effective method of management. METHODS: A retrospective review of 26 patients with unstable burst fractures in the thoracolumbar region (T11-L2) was performed; follow-up evaluation was obtained from 24 patients. Clinical follow-up examination was performed by the use of a questionnaire in which the patients were asked to rate their pain, ability to work, ability to perform in recreational activities, and their overall satisfaction with treatment. RESULTS: Mean follow-up time for the 24 patients was 34.3 months. Mean duration of hospitalization was 8.2 days; those patients who did not have injuries other than their spine fracture had a mean hospitalization time of 5.9 days. Kyphotic deformity could be corrected with hyperextension casting but tended to recur during the course of mobilization and healing. No correlation was found between kyphosis and clinical outcome. At final follow-up evaluation, 19 patients (79%) had little or no pain; 18 patients (75%) had returned to work; 18 (75%) stated that they had little or no restrictions in their ability to work, and 16 (67%) stated that they had little or no restrictions in their ability to participate in recreational activities. Only one patient (4%) reported being dissatisfied with the initial nonoperative treatment of his spine fracture. Ten patients were found to have evidence of spinous process widening on plain films; there was no significant difference in the clinical or radiographic outcome of these 10 patients when compared with the 14 others who did not have interspinous widening. CONCLUSIONS: Nonoperative management of thoracolumbar burst fractures with hyperextension casting or bracing was proven to be a safe and effective method of treatment in selected patients. Clinical results were favorable; no neurologic deterioration was observed; hospitalization times were minimized, and patient satisfaction was high. The authors do not believe that ligamentous injury of the posterior column is a contraindication to nonoperative management of thoracolumbar burst fractures.

Adolescent↗
PubMed1996

Evaluation of a CD5-specific immunotoxin for treatment of acute graft-versus-host disease after allogeneic marrow transplantation.

Acute graft-versus-host disease (GVHD) is most often treated with high dose glucocorticoids, but less than half of patients have durable overall improvement. Previous phase I and phase II studies suggested that treatment with a CD5-specific immunotoxin (XomaZyme-CD5 Plus) could ameliorate symptoms of GVHD. In a randomized, double-blind trial, we compared XomaZyme-CD5 Plus and glucocorticoids versus placebo and glucocorticoids as initial therapy for 243 patients who developed acute GVHD after allogeneic marrow transplantation. The study drug (XomaZyme. CD5-Plus or an identical appearing placebo) was administered at a dose of 0.1 mg/kg body weight on each of 14 consecutive days. All patients were treated concomitantly with a standard regimen of methylprednisolone. At the time of entry on study, 94% of patients had a rash, 56% had hyperbilirubinemia, 61% had diarrhea, and 84% had nausea and vomiting. At 3, 4, and 5 weeks after starting treatment, symptom severity was less in the CD5 group than in the placebo group. At 4 weeks, 40% of patients assigned to the CD5 group had complete response compared with 25% of those assigned to the control group (P = .019). At 6 weeks, 44% of patients assigned to the CD5 group had complete response as compared with 38% in the placebo group (P = .36). Clinical extensive chronic GVHD developed in 65% of patients in the CD5 group compared with 72% in the control group (P = .35). Survival at 1 year after treatment was 49% in the CD5 group and 45% in the control group (P = .68). Side effects required close monitoring and appropriate adjustment of treatment. The combined administration of a CD5-specific immunotoxin and glucocorticoids controls GVHD manifestations more effectively than treatment with glucocorticoids alone during the first 5 weeks after starting treatment. Use of this immunotoxin does not result in any long-term clinical benefit for patients with acute GVHD.

Acute Disease↗
PubMed1996

A phase I safety and pharmacokinetic study of a recombinant amino terminal fragment of bactericidal/permeability-increasing protein in healthy male volunteers.

A phase I pharmacokinetic and safety clinical trial of rBPI23, a recombinant amino terminal fragment of bactericidal/permeability-increasing protein, was conducted in healthy male volunteers. rBPI23 was administered as a 5 or 30 min infusion at doses of .1 to 1 mg/kg. The pharmacokinetics of rBPI23 in human subjects were described by a bi-exponential disposition function with evidence of concentration-dependent kinetics. The alpha half-life increased significantly with increasing dose, from 4-5 min at .1 mg/kg to 7-8 min at 1 mg/kg. The beta half-life varied between 18 and 29 min regardless of dose and the clearance varied from 5 to 10 mL/min/kg. Very little, if any, of the administered rBPI23 was excreted intact in the urine. Electrocardiograms, ionized calcium concentration, prothrombin and partial prothrombin times, hematologic parameters, and blood chemistries remained normal. Furthermore, no antibody response to rBPI23 was observed in any of the subjects.

Adolescent↗
PubMed1996

Improving drug use in rheumatic disorders.

A recent study concluded that approximately 50 elderly people are admitted to the major teaching hospital in Tasmania, Australia each year suffering from gastrointestinal bleeding related to the use of nonsteroidal anti-inflammatory drugs (NSAIDs). The aim of this study was to examine whether academic detailing, designed to encourage a rational approach to the prescribing of NSAIDs and performed by a pharmacist; could modify prescribing practices in the community. The intervention was conducted in Southern Tasmania, using the north of the state as a control area. The target group of all general practitioners (approximately 250) working in Southern Tasmania was sent educational material designed to assist in the appropriate prescribing of NSAIDs. A pharmacist then visited each general practitioner and discussed the rational use of NSAIDs directly with them. The outcome of the programme was measured using evaluation feedback from the general practitioners and pharmacoepidemiological data provided by (i) a state-wide pharmacoepidemiology database derived from community pharmacy records, and (ii) dispensing under the Pharmaceutical Benefits and Repatriation Pharmaceutical Benefits Schemes. The key variable examined was the defined daily dose (DDD) dispensed for the NSAIDs compared with paracetamol. The educational programme was very well received by the general practitioners. Changes in the prescribing of NSAIDs were evident in both study regions, but were more marked in the intervention area. For instance, the state-wide pharmacoepidemiological database indicated that the ratio of dispensed DDDs of NSAIDs: paracetamol declined from 3.00 to 2.59 in the intervention region and remained steadier (3.16 to 2.92) in the north of the state. The improvement was significantly greater in the intervention region. This study has revealed that an educational programme utilizing academic detailing by pharmacists can modify prescribing practices within the community setting.

Acetaminophen↗
PubMed1995

Inhibition of endotoxin-induced activation of the coagulation and fibrinolytic pathways using a recombinant endotoxin-binding protein (rBPI23).

A recombinant endotoxin-neutralizing protein, rBPI23, was shown to partially prevent endotoxin-induced activation of the fibrinolytic and coagulation systems in experimental endotoxemia in humans. In a placebo-controlled, blinded crossover study, eight volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg of body weight) and concurrently received either rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). rBPI23 treatment significantly lowered the endotoxin-induced fibrinolytic response, ie, reduced the release of tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor antigen, and complex formation of plasmin alpha 2-antiplasmin (P = .0078 for each). Plasminogen activator inhibitor activity was also reduced, but not significantly according to the Hochberg method (P = .0304). The endotoxin-induced activation of the procoagulant state as reflected by increase in F1 + 2 fragments and TAT complexes was blunted by rBPI23 infusion (P = .0391 [not significant according to the Hochberg method] and .0078, respectively). These results indicate that rBPI23 is capable of reducing both the activation of the fibrinolytic and the coagulation systems after low-dose endotoxin infusion in humans.

Anticoagulants↗
PubMed1995

Inhibition of endotoxin-induced cytokine release and neutrophil activation in humans by use of recombinant bactericidal/permeability-increasing protein.

To investigate the effects of a recombinant endotoxin-binding protein, bactericidal/permeability-increasing protein (rBPI23), on cytokine release and neutrophil activation in endotoxemia in humans, 8 volunteers were challenged twice with endotoxin and concurrently received either rBPI23 or placebo in a randomized, placebo controlled, double-blind crossover study, rBPI23 treatment significantly lowered circulating endotoxin levels (P = .02) and resulted in a significant reduction in the release of tumor necrosis factor (TNF), soluble TNF receptors p55 and p75, interleukin (IL)-6, IL-8 (P < .01 for each), and IL-10 levels (P = .02) but did not prevent the endotoxin-induced rise in body temperature. The early endotoxin-induced leukopenia was blunted (P = .08), and neutrophil degranulation, as measured by circulating levels of elastase/alpha 1-antitrypsin complexes (P = .03) and lactoferrin (P < .01), was largely prevented by rBPI23. The results of this study indicate that rBPI23 is capable of neutralizing many of the biologic effects of endotoxin in humans.

Antimicrobial Cationic Peptides↗
PubMed1995

Plasma bactericidal/permeability-increasing protein concentrations in critically ill children with the sepsis syndrome.

Bactericidal/permeability-increasing protein (BPI) is a neutrophil azurophilic granule component that is bactericidal towards Gram-negative bacteria and inhibits lipopolysaccharide-mediated inflammatory responses. We conducted a prospective study to measure plasma BPI concentrations in 36 critically ill children with and without the sepsis syndrome. Plasma BPI concentrations ranged from 0.5 to 452 ng/ml. Patients with the sepsis syndrome had higher median plasma BPI concentrations than critically ill controls (5.1 vs. 1.8 ng/ml, P = 0.006). Patients with organ system failure had higher median plasma BPI concentrations than those with no organ system failure (4.5 vs. 1.3 ng/ml, P = 0.001). Plasma BPI concentrations were positively associated with pediatric risk of mortality score (P = 0.03, rs = 0.4). These data provide the first clinical insights regarding the role of endogenous BPI production in critically ill children and suggest that BPI may play an important role in host defenses.

Anti-Bacterial Agents↗
PubMed1994

Interleukin-2 suppresses activated macrophage intracellular killing activity by inducing macrophages to secrete TGF-beta.

Phorbol myristate acetate (PMA) treatment of an EL-4 thymoma cell line (EL-4FARRAR) induced secretion of a factor that inhibited intracellular killing of Leishmania major amastigotes by activated macrophages. Analysis of the cytokines produced by EL-4 cells after PMA stimulation identified interleukin-2 (IL-2, 2500 U/ml), IL-4 (1280 U/ml), interferon-gamma (IFN-gamma; 100 U/ml), and granulocyte-macrophage colony-stimulating factor (GM-CSF; 50 U/ml). Neither tumor necrosis factor nor transforming growth factor beta (TGF-beta) was detected. Each of the cytokines present in EL-4 fluids was assessed for capacity to activate macrophages for destruction of parasites or to suppress intracellular killing. IFN-gamma and GM-CSF both activated macrophages to kill Leishmania; IL-2 and IL-4 had no activity for induction of this antimicrobial effector function. IL-2 and IL-4 were tested for their capacity to inhibit lymphokine- or IFN-gamma-induced destruction of L. major by macrophages: IL-4 was ineffective, but IL-2 markedly suppressed the activation of macrophages for intracellular killing. Addition of > or = 10 U/ml of IL-2 at the time of infection, or up to 4 h before, blocked up to 100% of the capacity of activated macrophages to kill intracellular amastigotes. Immunoaffinity treatment of EL-4 fluids with anti-IL-2 antibody resulted in > 80% reduction in suppression of intracellular killing. The suppressive effects of IL-2 were not direct, but mediated by TGF-beta. IL-2 induced resident peritoneal macrophages to secrete > 5000 pg/ml TGF-beta 1, a quantity that is > 500-fold higher than constitutive background levels (20-40 pg/ml) and is sufficient to block intracellular killing activities. This increase in secretion of TGF-beta was not dependent increases in TGF-beta 1 mRNA. Treatment of cultures with EL-4 fluids or recombinant IL-2 in the presence of antibody to TGF-beta 1 blocked the suppressive activity of both. Thus, IL-2 was the major suppressor factor in EL-4 fluids, and it acted indirectly through the induction and autocrine action of TGF-beta.

Animals↗
PubMed1994

Nitric oxide: cytokine-regulation of nitric oxide in host resistance to intracellular pathogens.

To discover how nitric oxide (NO) synthesis is controlled in different tissues as cells within these tissues combat intracellular pathogens, we examined three distinctively different experimental murine models designed for studying parasite-host interactions: macrophage killing of Leishmania major; nonspecific protection against tularemia (Francisella tularensis) by Mycobacterium bovis (BCG); and specific vaccine-induced protection against hepatic malaria with Plasmodium berghei. Each model parasite and host system provides information on the source and role of NO during infection and the factors that induce or inhibit its production. The in vitro assay for macrophage antimicrobial activity against L. major identified cytokines involved in regulating NO-mediated killing of this intracellular protozoan. L. major induced the production of two competing cytokines in infected macrophages: (1) the parasite activated the gene for tumor necrosis factor (TNF), and production of TNF protein was enhanced by the presence of interferon-gamma (IFN-gamma). TNF then acted as a autocrine signal to amplify IFN-gamma-induced production of NO; and (2) the parasite upregulated production of transforming growth factor-beta (TGF-beta), which blocked IFN-gamma-induced production of NO. Whether parasite-induced TNF (parasite destruction) or TGF-beta (parasite survival) prevailed depended upon the presence and quantity of IFN-gamma at the time of infection. The relationship between NO production in vivo and host resistance to infection was demonstrated with M. bovis (BCG).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1993

Comparison of two dentifrices in the control of chlorhexidine-induced stain.

An eight-week, double-blind, parallel and unsupervised clinical study was conducted to compare the ability of two dentifrices, Arm & Hammer Dental Care toothpaste and Crest toothpaste, to prevent the formation of stain induced by the twice daily use of 0.12% chlorhexidine gluconate (Peridex). Stain formation was evaluated through the use of a new index (Modified Stain Index) designed to selectively detect stain of the proximal and facial surfaces of the anterior teeth. Examinations of stain formation were conducted at two-week intervals for a total of eight weeks. The results indicated equivalent stain prevention benefits for Arm & Hammer Dental Care and Crest when evaluated during eight weeks of chlorhexidine therapy. The modified stain index was shown to be valuable for discriminating location and intensity of early stain formation.

Adult↗
PubMed1992

The motivational benefits of a dentifrice containing baking soda and hydrogen peroxide.

Twenty-two family practice dentists, in a large metropolitan area, were recruited to act as independent examiners in a study to evaluate the compliance of their patients to accept a good oral hygiene regimen with the use of a fluoride dentifrice, containing hydrogen peroxide and baking soda, dispensed from a dual dispensing package. To evaluate compliance, the dentists attended an orientation seminar and were trained to assess gingival health using the CPITN periodontal probe. Each dentist evaluated the gingival health status of five to seven of his own patients, initially and after one and three months of product use following hygiene instruction and product assignment. One-hundred and thirty-one patients successfully completed the study. After one month of using the hydrogen peroxide/baking soda toothpaste, the mean reduction in bleeding sites was 53%; at three months the reduction was 62%. The hydrogen peroxide/baking soda dentifrice was well accepted by dentist and patient, and a discernible improvement in oral health of the patients was achieved when the product was used in a conscientious oral hygiene program.

Adult↗
PubMed1991

Differential susceptibility of activated macrophage cytotoxic effector reactions to the suppressive effects of transforming growth factor-beta 1.

We examined the effects of TGF-beta 1 on induction of several activated macrophage antimicrobial activities against the protozoan parasite Leishmania, and on induction of tumoricidal activity against the fibrosarcoma tumor target 1023. TGF-beta by itself did not affect the viability of either the intracellular or extracellular target in concentrations up to 200 ng/ml. As little as 1 ng/ml TGF-beta, however, suppressed more than 70% of the intracellular killing activity of macrophages treated with lymphokines. In contrast, more than 100 ng/ml TGF-beta was required to suppress intracellular killing by cells activated with an equivalent amount of recombinant IFN-gamma. Addition of TGF-beta for up to 30 min after exposure to activation factors significantly reduced macrophage killing of intracellular parasites. Pretreatment of macrophages with TGF-beta was even more effective: treatment of cells with TGF-beta for 4 h before addition of activation factors abolished all macrophage intracellular killing activity. Regardless of treatment sequence, however, TGF-beta had absolutely no effect, at any concentration tested, on activated macrophage resistance to infection induced by lymphokines or by the cooperative interaction of IFN-gamma and IL-4. Effects of TGF-beta on tumoricidal activity of activated macrophages was intermediate to that of its effects on intracellular killing or resistance to infection. Lymphokine-induced tumor cytotoxicity was marginally (25%) affected by TGF-beta; 200 ng/ml was able to suppress IFN-gamma-induced tumoricidal activity by 40%. Thus, TGF-beta dramatically suppressed certain activated macrophage cytotoxic effector reactions, but was only partially or not at all effective against others, even when the same activation agent (IFN-gamma) was used. The biochemical target for TGF-beta suppressive activity in these reactions may be the pathway for nitric oxide production from L-arginine, because TGF-beta also inhibited the generation of nitric oxide by cytokine-activated macrophages.

Animals↗