Biomedical subjects

S R Wisniewski

Publications and source records attributed to S R Wisniewski.

At least 37 records · Page 2Linked to original sources

PubMed2000

Intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 are increased in the plasma of children with sepsis-induced multiple organ failure.

OBJECTIVES: To determine concentrations of circulating adhesion molecules endothelial (E)-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 in children with sepsis-induced multiple organ failure (MOF), and to determine associations among increased concentrations of these circulating adhesion molecules and important outcome measures. DESIGN: Prospective study. SETTING: University pediatric intensive care unit. PATIENTS: A total of 77 consecutive children with sepsis and 14 acutely ill children without sepsis. INTERVENTIONS: Plasma E-selectin, ICAM-1, and VCAM-1 concentrations and organ failure index (indicating number of failed organ systems) were determined in 77 children on days 1 and 3 of sepsis, and in 14 control children on pediatric intensive care unit day 1. Multivariate logistic regression analysis was used to determine associations between adhesion molecule concentrations and clinically relevant outcome measures. MEASUREMENTS AND RESULTS: Plasma concentrations of E-selectin, ICAM-1, and VCAM-1 were increased in children with sepsis vs. control on day 1 (p < .05). Plasma VCAM-1 (but not ICAM-1 or E-selectin) was increased in children with more than three organ failures vs. children with less than three organ failures (p < .05). Plasma ICAM-1 and VCAM-1 (but not E-selectin) concentrations independently predicted number of organs failed and development of more than three organ failures. Plasma ICAM-1 and VCAM-1 also predicted mortality and development of sequential (pulmonary/hepatic/renal) MOF (p < .05). CONCLUSIONS: The pronounced and persistent increase in plasma VCAM-1 and ICAM-1 that occurs in children with sepsis and persistent MOF may indicate a phenotypic change in endothelium toward a more proinflammatory state. Alternatively, the source for these adhesion molecules may be activated leukocytes and other cell types. Future studies are required to determine the role of ICAM-1 and VCAM-1 in the pathogenesis of sepsis-induced MOF.

Adolescent↗

PubMed2000

No long-term benefit from hypothermia after severe traumatic brain injury with secondary insult in rats.

OBJECTIVES: To evaluate the effect of application of transient, moderate hypothermia on outcome after experimental traumatic brain injury (TBI) with a secondary hypoxemic insult. DESIGN: Prospective, randomized study. SETTING: University-based animal research facility. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: All rats were subjected to severe TBI followed by 30 mins of moderate hypoxemia, associated with mild hypotension. Rats were randomized to three groups: a) normothermia (37 degrees C + 0.5 degrees C); b) immediate hypothermia (32 degrees C +/- 0.5 degrees C initiated after trauma, before hypoxemia); and c) delayed hypothermia (32 degrees C +/- 0.5 degrees C after hypoxemia). The brain temperature was controlled for 4 hrs after TBI and hypoxemia. MEASUREMENTS AND MAIN RESULTS: Animals were evaluated after TBI for motor and cognitive performance using beam balance (days 1-5 after TBI), beam walking (days 1-5 after TBI), and Morris Water Maze (days 14-18 after TBI) assessments. On day 21 after TBI, rats were perfused with paraformaldehyde and brains were histologically evaluated for lesion volume and hippocampal neuron counts. All three groups showed marked deficits in beam balance, beam walking, and Morris Water Maze performance. However, these deficits did not differ between groups. There was no difference in lesion volume between groups. All animals had significant hippocampal neuronal loss on the side ipsilateral to injury, but this loss was similar between groups. CONCLUSIONS: In this rat model of severe TBI with secondary insult, moderate hypothermia for 4 hrs posttrauma failed to improve motor function, cognitive function, lesion volume or hippocampal neuronal survival. Combination therapies may be necessary in this difficult setting.

Animals↗

PubMed2000

Effect of neutropenia and granulocyte colony stimulating factor-induced neutrophilia on blood-brain barrier permeability and brain edema after traumatic brain injury in rats.

OBJECTIVE: Granulocyte colony stimulating factor (GCSF) has been used to increase systemic absolute neutrophil count (ANC) in patients with severe traumatic brain injury to reduce nosocomial infection risk. However, the effect of increasing systemic ANC on the pathogenesis of experimental traumatic brain injury has not been studied. Thus, we evaluated the effect of systemic ANC on blood-brain barrier (BBB) damage and brain edema after traumatic brain injury in rats. DESIGN: Experimental study. SETTING: Research laboratory at the University of Pittsburgh, PA. SUBJECTS: Forty-three adult male Sprague-Dawley rats. INTERVENTIONS: Protocol I: rats were randomized to receive either vinblastine sulfate to reduce ANC, GCSF to increase ANC, or saline before controlled cortical impact (CCI) of moderate overall severity. Evans blue was used to assess BBB damage at 4-24 hrs after CCI. Protocol II: rats received GCSF or saline before CCI. Brain edema was estimated at 24 hrs using wet - dry) / wet weight method. Protocol III: rats received GCSF or saline before CCI. Brain neutrophil accumulation was estimated at 24 hrs using a myeloperoxidase assay. MEASUREMENTS AND MAIN RESULTS: Physiologic variables were controlled before CCI was maintained at normal in all animals before traumatic brain injury. No rats were anemic, hypoglycemic, or hypotensive before CCI. Protocol I: compared with control, systemic ANC decreased in vinblastine-treated rats and increased in GCSF-treated rats. BBB damage correlated with systemic ANC. Protocol II: mean systemic ANC before traumatic brain injury increased 15-fold in rats given GCSF vs. control; however no difference in brain edema was observed at 24 hrs after injury between groups. Protocol III: median systemic ANC at the time of CCI was increased ten-fold in rats given GCSF vs. control. No difference in brain myeloperoxidase activity 24 hrs after CCI was observed in rats treated with GCSF vs. control. CONCLUSIONS: Systemic ANC influences BBB damage after traumatic brain injury produced by CCI. Because BBB damage and brain edema are discordant, mechanisms other than BBB damage likely predominate in the pathogenesis of brain edema after contusion. The implications of increased BBB permeability with the administration of GCSF in our model remains to be determined. Increasing systemic ANC before CCI with GCSF administration does not increase posttraumatic brain neutrophil accumulation or brain edema after CCI in rats. The finding that neutrophil infiltration is not enhanced by systemic neutrophilia suggests that the ability of GCSF-stimulated neutrophils to migrate into injured tissue may be impaired. Further studies are needed to evaluate the effects of GCSF administration on secondary injury and functional outcome in experimental models of traumatic brain injury.

Animals↗

PubMed1999

Psychiatric medication and abnormal behavior as predictors of progression in probable Alzheimer disease.

OBJECTIVE: To examine whether the use of psychiatric medication and the presence of abnormal behaviors affects the progression of Alzheimer disease. DESIGN: Cross-sectional with longitudinal follow-up and the likelihood of arriving at 4 end points: (1) Mini-Mental State Examination score of 9 or lower; (2) Blessed Dementia Rating Scale score of 15 or higher for activities of daily living; (3) nursing home admission; and (4) death, evaluated using a proportional hazard model with 9 variables: psychosis, insomnia, wandering, aggression, psychomotor agitation, depression, and use of antidepressants, antipsychotic agents, or sedatives/hypnotics. SETTING: Multidisciplinary dementia research clinic. PATIENTS: We examined baseline and follow-up behavioral symptoms and the use of psychiatric medication in 179 mildly to moderately impaired patients with probable Alzheimer disease participating in a longitudinal study of dementia. Patients were observed from 2.4 to 172 months (mean duration +/- SD, 49.5+/-27.4 months). RESULTS: Nine patients (5%) were taking sedatives/ hypnotics; 16 (9%), antipsychotic agents; and 22 (12%), antidepressants at study entry. Patients taking antipsychotic agents had lower Mini-Mental State Examination scores and higher Blessed Dementia Rating Scale scores for activities of daily living than patients not taking any medication. Using proportional hazard analysis with time-dependent covariates for individual psychiatric symptoms and medications, we found that the development of psychosis was associated with functional decline (time to Blessed Dementia Rating Scale score of > or =15), institutionalization, aggression, and agitation with functional decline after adjusting for age at study entry, education, Mini-Mental State Examination scores, and Blessed Dementia Rating Scale scores. Use of antipsychotic medication was associated with functional decline, and sedatives/hypnotics with death. Neither the presence of psychiatric symptoms nor use of medication was associated with rate of cognitive decline (time to Mini-Mental State Examination score of < or =9). CONCLUSIONS: These findings indicate that the use of antipsychotic agents and sedatives can affect the natural course of Alzheimer disease. Psychosis, agitation, and aggression are important predictors of outcome, even when the effects of medication to treat them is taken into account.

Aged↗

PubMed1999

Selecting, developing, and evaluating research instruments.

The goal of this paper is to provide researchers who are not experts in psychometric theory with a concise guide to instrument selection, development and evaluation. Issues of context - factors related to the setting or population in which an instrument will be used - and psychometrics - the functioning of an instrument within a given context - are reviewed and discussed. Finally, four categories or types of instruments, and the psychometric analyses that are necessary for establishing the reliability and validity of each type, are described.

Humans↗

PubMed1999

Quinolinic acid in the cerebrospinal fluid of children after traumatic brain injury.

OBJECTIVE: To measure quinolinic acid, a macrophage-derived neurotoxin, in the cerebrospinal fluid (CSF) of children after traumatic brain injury (TBI) and to correlate CSF quinolinic acid concentrations to clinically important variables. DESIGN: A prospective, observational study. SETTING: The pediatric intensive care unit in Children's Hospital of Pittsburgh, a tertiary care, university-based children's hospital. PATIENTS: Seventeen critically ill children following severe TBI (Glasgow Coma Scale score <8) whose care required the placement of an intraventricular catheter for continuous drainage of CSF. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients ranged in age from 2 mos to 16 yrs (mean 6.0 yrs). CSF was collected immediately on placement of the ventricular catheter and daily thereafter. Quinolinic acid concentration was measured by gas chromatography/mass spectroscopy in 69 samples (4.0 +/- 0.4 [SEM] samples per patient). CSF quinolinic acid concentration progressively increased after injury (p = .034, multivariate analysis) and was increased in nonsurvivors vs. survivors (p = .002, multivariate analysis). CSF quinolinic acid concentration was not associated with age. Although overall CSF quinolinic acid concentration was not associated with shaken injury (p = .16, multivariate analysis), infants suffering with shaken infant syndrome had increased admission CSF quinolinic acid concentrations compared with children with accidental mechanisms of injury (p = .027, Mann-Whitney Rank Sum test). CONCLUSIONS: A large and progressive increase in the macrophage-derived neurotoxin quinolinic acid is seen following severe TBI in children. The increase is strongly associated with increased mortality. Increased CSF quinolinic acid concentration on admission in children with shaken infant syndrome could reflect a delay in presentation to medical attention or age-related differences in quinolinic acid production. These findings raise the possibility that quinolinic acid may play a role in secondary injury after TBI in children and suggest an interaction between inflammatory and excitotoxic mechanisms of injury following TBI.

Accidents, Traffic↗

PubMed1999

Microbiologic yields and complication rates of vitreous needle aspiration versus mechanized vitreous biopsy in the Endophthalmitis Vitrectomy Study.

PURPOSE: To compare the microbiologic yields and complication rates associated with vitreous needle tap and vitreous biopsy in the Endophthalmitis Vitrectomy Study (EVS). METHODS: Of 420 EVS patients with postoperative endophthalmitis, 201 received immediate vitreous tap or biopsy (without pars plana vitrectomy) by random assignment and 193 completed 9-12 months of follow-up. Vitreous specimens were obtained by biopsy with a 20-gauge vitrectomy cutting instrument or by needle tap with a 22-27-gauge needle. If resistance to aspiration by needle tap was noted, a vitreous biopsy was performed. RESULTS: Of 201 patients undergoing tap or biopsy, 70 (35%) had needle tap, 127 (63%) had mechanized biopsy, and 4 (2%) had initial needle tap that was aborted to mechanized biopsy ("abort" eyes). Intraoperative hyphema occurred in 2 tap eyes (3%), 3 biopsy eyes (2%), and 0 (0%) abort eyes. Postoperative retinal detachment developed in 8 (11%) tap eyes, 10 (8%) biopsy eyes, and 0 (0%) abort eyes (not significant). Respective rates of culture and gram stain positivity were 69% and 42% in tap eyes and 66% and 41% in biopsy eyes (not significant). The rate of severe visual loss (final acuity <5/200) was significantly higher in tap eyes (16 eyes, 24%) compared with biopsy eyes (13 eyes, 11%) and abort eyes (0 eyes, 0%; P = 0.043). The difference was largely explained by the greater proportion of virulent organisms in the tap eyes compared with biopsy eyes. When visual acuity outcome was defined by other thresholds (20/40 and 20/100), the difference was not significant. CONCLUSIONS: This study showed no significant differences between mechanized vitreous biopsy and needle tap with respect to microbiologic yield, operative complications, short-term (9-12 months) retinal detachment risk, or visual outcome. Choice of vitreous sampling procedure must depend on the clinical judgment of the surgeon.

Biopsy, Needle↗

PubMed1999

Measurement of hemostatic indexes in conjunction with transcranial doppler sonography in patients with ventricular assist devices.

BACKGROUND AND PURPOSE: Clinical thromboembolism (TE) remains an impediment to the chronic application of ventricular assist devices (VADs). Microembolic signals (MES) have been detected by transcranial Doppler ultrasound (TCD) in patients with VADs, although their origin and relation to TE remain undefined. We have investigated the hypothesis that hemostatic alterations are related to MES and that MES are associated with TE in a group of 27 VAD patients. METHODS: Indexes of coagulation, fibrinolysis, and cellular activation and aggregation were measured before and during the VAD implantation period in conjunction with TCD. Groups were defined on the basis of presence of MES, degree of MES showering, and incidence of TE. RESULTS: MES were observed in 67 (58%) of 115 of individual postoperative TCD measurements and in 21 (78%) of 27 patients. Of patients with TE, 10 (83%) of 12 had detectable MES compared with 11 (73%) of 15 patients without TE (P=0.66). MES were significantly associated with elevated thrombin generation during the implantation period, as reflected by plasma prothrombin fragment F1.2. Elevations in indexes of coagulation, platelet activation, and fibrinolysis relative to normal control subjects were found for patients with VADs with and without detected MES. CONCLUSIONS: Although no significant relation between MES and TE in VAD patients was found, the data support the hypothesis that MES are related to increased hemostatic activity in this patient group despite aggressive anticoagulant therapy.

Adolescent↗

PubMed1999

Effects of norepinephrine on the renal vasculature in normal and endotoxemic dogs.

Septic shock is often complicated by systemic hypotension despite normal or increased cardiac output. Restoration of arterial pressure usually requires the administration of systemic vasopressor agents, such as norepinephrine. However, because norepinephrine induces vasoconstriction in other vascular beds, it may decrease visceral blood flow, impairing visceral organ function. Because sepsis is often associated with impaired peripheral vascular responsiveness, we hypothesized that, unlike in normal circulatory conditions, norepinephrine would improve visceral organ blood flow in sepsis by selectively increasing organ perfusion pressure. Thus, in nine pentobarbital-anesthetized, mechanically ventilated dogs, we measured the effect of norepinephrine infusion (0.3 microgram/kg/min) on renal, hepatic, and portal steady-state pressure-flow relations (P/Q) and the dynamic vascular P/Q, created by transient inferior vena caval occlusion, under basal and endotoxic conditions. Norepinephrine increased organ perfusion pressures during both control and endotoxemic conditions. However, even after controlling for the pressure effect using a general linear model, NE was associated with an increase in renal blood flow both before and after endotoxin administration. We conclude that, unlike the effects of administering norepinephrine under baseline conditions, norepinephrine infusion during endotoxic shock actually increases renal blood flow and that this effect is not the result of an increase in perfusion pressure alone.

Animals↗

PubMed1999

Inducible nitric oxide synthase is an endogenous neuroprotectant after traumatic brain injury in rats and mice.

Nitric oxide (NO) derived from the inducible isoform of NO synthase (iNOS) is an inflammatory product implicated both in secondary damage and in recovery from brain injury. To address the role of iNOS in experimental traumatic brain injury (TBI), we used 2 paradigms in 2 species. In a model of controlled cortical impact (CCI) with secondary hypoxemia, rats were treated with vehicle or with 1 of 2 iNOS inhibitors (aminoguanidine and L-N-iminoethyl-lysine), administered by Alzet pump for 5 days and 1. 5 days after injury, respectively. In a model of CCI, knockout mice lacking the iNOS gene (iNOS(-/-)) were compared with wild-type (iNOS(+/+)) mice. Functional outcome (motor and cognitive) during the first 20 days after injury, and histopathology at 21 days, were assessed in both studies. Treatment of rats with either of the iNOS inhibitors after TBI significantly exacerbated deficits in cognitive performance, as assessed by Morris water maze (MWM) and increased neuron loss in vulnerable regions (CA3 and CA1) of hippocampus. Uninjured iNOS(+/+) and iNOS(-/-) mice performed equally well in both motor and cognitive tasks. However, after TBI, iNOS(-/-) mice showed markedly worse performance in the MWM task than iNOS(+/+) mice. A beneficial role for iNOS in TBI is supported.

Animals↗

PubMed1999

Apolipoprotein E polymorphism: A new genetic marker of hip fracture risk--The Study of Osteoporotic Fractures.

Hip fractures are common and devastating events. The apolipoprotein E*4 (APOE) allele, associated with Alzheimer's disease, has also been associated with osteoporosis in hemodialysis patients. We prospectively studied 1750 women, age >/=65 years, who underwent measurements of hip and calcaneal bone mineral density (BMD), were typed for APOE and followed for approximately 7.0 years for the occurrence of fractures and falls. Women with at least one APOE*4 allele had an increased risk of hip fracture, relative hazard (RH) (95% confidence interval) = 1.90 (1.05-3.41) and wrist fracture, RH = 1.67 (1.01-2.77) compared with women without APOE*4, even after adjusting for age, cognitive function, falling, and BMD. The effect of APOE*4 on hip fracture was greatest among women with additional (>/=3) other risk factors. Women with an APOE*4 allele were also likely to report a maternal history of fracture. The average number of falls per year did not differ by APOE*4: 0.46 for APOE*4 women and 0.41 for women without an APOE*4 allele. Women with an APOE*4 allele experienced greater weight loss which contributed to faster rates of bone loss. We conclude that women with the APOE*4 polymorphism are at substantially increased risk of hip and wrist fracture that is not explained by bone density, impaired cognitive function, or falling. Possible alternate explanations include an effect of APOE on vitamin K, bone turnover, or weight loss. The APOE polymorphism may be a candidate gene for hip fractures among community dwelling nondemented women.

Accidental Falls↗

PubMed1998

Additional procedures after the initial vitrectomy or tap-biopsy in the Endophthalmitis Vitrectomy Study.

OBJECTIVE: The study aimed to assess the frequency, indications, and outcome of additional ocular procedures after initial treatment of vitrectomy (VIT) or tap-biopsy (TAP) for patients with endophthalmitis after cataract extraction. DESIGN: The study design was an analysis of observational data collected as part of a multicenter, randomized clinical trial. PARTICIPANTS: Of the 420 patients enrolled in the Endophthalmitis Vitrectomy Study, the 148 who had additional procedures were compared with the 272 who did not. MAIN OUTCOME MEASURES: The types, indications, and number of additional ocular procedures were assessed. A masked examiner measured visual acuity 9 to 12 months after study entry. RESULTS: Within 1 week of study entry, 8% of VIT eyes and 13% of TAP eyes underwent additional procedures, 14% for complications of the initial procedure and 86% for worsening ocular inflammation or infection. Cultures were obtained in 33 of the 38 eyes operated on for worsening inflammation or infection and were positive in 42%. Cultures obtained from the early additional procedures were positive more frequently in eyes with an initial TAP (71%) than in eyes with an initial VIT (13%). Both virulence of initial microbiologic organism isolated and poor presenting vision were risk factors for requirement of reoperation. In all cases in which a single organism was cultured at the initial procedure, when the reculture was positive, it was the same organism. Late additional procedures (after 7 days) were required in 27% of patients. Visual outcome was much worse for eyes that had an additional procedure compared to eyes that did not, and this was especially the case for eyes that had an early additional procedure. Only 15% of eyes that had an early additional procedure achieved 20/40 visual acuity as compared to 57% of eyes that did not. CONCLUSION: Need for an additional procedure was a marker of more severe disease, and patients who underwent additional procedures achieved poorer visual acuity at final follow-up.

Bacteria↗

PubMed1998

Interstitial adenosine, inosine, and hypoxanthine are increased after experimental traumatic brain injury in the rat.

Adenosine is a putative neuroprotectant in ischemia, but its role after traumatic brain injury (TBI) is not clear. Metabolites of adenosine, particularly inosine and hypoxanthine, are markers of ischemia and energy failure. Adenosine triphosphate (ATP) breakdown early after injury and metabolism of cyclic adenosine monophosphate (cAMP) are potential sources of adenosine. Further delineation of the magnitude, location, time course, and source of production of adenosine after TBI is needed. We measured adenosine, inosine, and hypoxanthine in brain interstitial fluid after controlled cortical impact (CCI) in the rat. Rats (n = 15) were prepared for TBI induced by CCI. A microdialysis probe was placed in the cortex, and samples were collected every 10 min. After 3 h of equilibration, the catheter was removed, CCI was performed (4 m/sec, depth 2.5 mm), and the catheter was replaced. In the shams, the catheter was removed and replaced without CCI. The injury group included rats (n = 10) subjected to CCI. Within the injury group, the microdialysis probe was placed in the center of the eventual contusion (center, n = 5) or in the penumbral region (penumbra, n = 5). Purine metabolites were measured using ultraviolet-based high-pressure liquid chromatography. Adenosine, inosine, and hypoxanthine were dramatically increased after injury (61-fold, 37-fold, and 16-fold, respectively sham, all p < 0.05, two-way analysis of variance for repeated measures). No changes in cAMP were observed (p = 0.62 vs. sham). Adenosine peaked in the first 20 min and returned to near baseline 40 min, whereas inosine and hypoxanthine peaked at 30 min and remained increased for 40 min after CCI. Interstitial brain adenosine, inosine, and hypoxanthine were increased early after CCI in rats in the contusion and penumbra. ATP breakdown is a potential source of adenosine in this early period while metabolism of cAMP does not appear to play a role. Confirmation of these data in humans may suggest new strategies targeting this important metabolic pathway.

Adenosine↗

PubMed1998

Soluble adhesion molecules in CSF are increased in children with severe head injury.

Leukocyte-endothelial adhesion molecules, critical to the development of acute inflammation, are expressed in brain as part of the acute inflammatory response to traumatic brain injury (TBI). We measured the concentrations of the adhesion molecules P-selectin, ICAM-1, E-selectin, L-selectin, and VCAM-1 in ventricular cerebrospinal fluid (CSF) from children with severe TBI (Glasgow coma score < 8) and compared these findings with those from children with bacterial meningitis. P-selectin, an adhesion molecule associated with ischemia/reperfusion, was increased in children with TBI versus meningitis and control. Univariate and multivariate regression analyses demonstrated associations between CSF P-selectin and child abuse and age of < 4 years, and a significant, independent association between CSF intercellular adhesion molecule-1 (ICAM-1) and child abuse. These results are consistent with a specific acute inflammatory component to TBI in children. Future studies of secondary injury mechanisms and therapy after TBI should assess on the roles of P-selectin and ICAM-1 in injury and repair processes in brain after TBI.

Adolescent↗

PubMed1998

Quinolinic acid is increased in CSF and associated with mortality after traumatic brain injury in humans.

We tested the hypothesis that quinolinic acid, a tryptophan-derived N-methyl-D-aspartate agonist produced by macrophages and microglia, would be increased in CSF after severe traumatic brain injury (TBI) in humans, and that this increase would be associated with outcome. We also sought to determine whether therapeutic hypothermia reduced CSF quinolinic acid after injury. Samples of CSF (n = 230) were collected from ventricular catheters in 39 patients (16 to 73 years old) during the first week after TBI, (Glasgow Coma Scale [GCS] < 8). As part of an ongoing study, patients were randomized within 6 hours after injury to either hypothermia (32 degrees C) or normothermia (37 degrees C) treatments for 24 hours. Otherwise, patients received standard neurointensive care. Quinolinic acid was measured by mass spectrometry. Univariate and multivariate analyses were used to compare CSF quinolinic acid concentrations with age, gender, GCS, time after injury, mortality, and treatment (hypothermia versus normothermia). Quinolinic acid concentration in CSF increased maximally to 463 +/- 128 nmol/L (mean +/- SEM) at 72 to 83 hours after TBI. Normal values for quinolinic acid concentration in CSF are less than 50 nmol/L. Quinolinic acid concentration was increased 5- to 50-fold in many patients. There was a powerful association between time after TBI and increased quinolinic acid (P < 0.00001), and quinolinic acid was higher in patients who died than in survivors (P = 0.003). Age, gender, GCS, and treatment (32 degrees C versus 37 degrees C) did not correlate with CSF quinolinic acid. These data reveal a large increase in quinolinic acid concentration in CSF after TBI in humans and raise the possibility that this macrophage-derived excitotoxin may contribute to secondary damage.

Adolescent↗

PubMed1997

Treatment of traumatic brain injury with moderate hypothermia.

BACKGROUND: Traumatic brain injury initiates several metabolic processes that can exacerbate the injury. There is evidence that hypothermia may limit some of these deleterious metabolic responses. METHODS: In a randomized, controlled trial, we compared the effects of moderate hypothermia and normothermia in 82 patients with severe closed head injuries (a score of 3 to 7 on the Glasgow Coma Scale). The patients assigned to hypothermia were cooled to 33 degrees C a mean of 10 hours after injury, kept at 32 degrees to 33 degrees C for 24 hours, and then rewarmed. A specialist in physical medicine and rehabilitation who was unaware of the treatment assignments evaluated the patients 3, 6, and 12 months later with the use of the Glasgow Outcome Scale. RESULTS: The demographic characteristics and causes and severity of injury were similar in the hypothermia and normothermia groups. At 12 months, 62 percent of the patients in the hypothermia group and 38 percent of those in the normothermia group had good outcomes (moderate, mild, or no disabilities). The adjusted risk ratio for a bad outcome in the hypothermia group was 0.5 (95 percent confidence interval, 0.2 to 1.2). Hypothermia did not improve the outcomes in the patients with coma scores of 3 or 4 on admission. Among the patients with scores of 5 to 7, hypothermia was associated with significantly improved outcomes at 3 and 6 months (adjusted risk ratio for a bad outcome, 0.2; 95 percent confidence interval, 0.1 to 0.9 at both intervals), although not at 12 months (risk ratio, 0.3; 95 percent confidence interval, 0.1 to 1.0). CONCLUSIONS: Treatment with moderate hypothermia for 24 hours in patients with severe traumatic brain injury and coma scores of 5 to 7 on admission hastened neurologic recovery and may have improved the outcome.

Adolescent↗

PubMed1997

Evaluation of microbiological diagnostic techniques in postoperative endophthalmitis in the Endophthalmitis Vitrectomy Study.

OBJECTIVE: To analyze the data for cultures and Gram stains prospectively collected by protocol in the Endophthalmitis Vitrectomy Study. DESIGN: Cultures of aqueous, undiluted vitreous, and (for patients who underwent vitrectomy) vitrectomy cassette fluid obtained from 420 patients were prepared on chocolate agar, in thioglycolate broth, and on Sabouraud dextrose agar; Gram stains of the aqueous and undiluted vitreous were made. Criteria were devised to distinguish true pathogens (confirmed positive cultures) from contaminants. SETTING: Private and university-based retina-vitreous practices and corresponding microbiology laboratories. RESULTS: Compared with the aqueous, undiluted vitreous produced a higher percentage of confirmed positive cultures and higher colony counts on chocolate agar and was more frequently the only source of a positive culture from the eye. Nevertheless, the aqueous and vitrectomy cassette fluid were the only source of a positive culture from the eye in 4.2% and 8.9% of eyes, respectively. The overall yields of chocolate agar and thioglycolate broth were similar. A positive Gram stain from the aqueous or undiluted vitreous was highly predictive of a positive culture from the eye, but a negative Gram stain had little predictive value for the culture result. The overall rate of laboratory-confirmed infection was not statistically significantly higher in the vitrectomy group than in the tap or biopsy group. CONCLUSIONS: The vitreous was a richer source of positive cultures and high colony counts than was the aqueous, either because it is more supportive of bacterial growth or because a somewhat larger inoculum of the vitreous than of aqueous could be obtained. The result of Gram stain should not determine the choice of antibiotic drugs in the treatment of endophthalmitis. Vitrectomy, with culture of the vitrectomy cassette fluid, did not produce significantly more positive cultures than tap or biopsy material, and the procedure should not be performed to improve the microbiological yield.

Aqueous Humor↗

PubMed1997

The role of adenosine during the period of delayed cerebral swelling after severe traumatic brain injury in humans.

Cerebrovascular failure with an increase in cerebral blood volume or hyperemia contributes delayed cerebral swelling after severe traumatic brain injury (TBI) in humans. One mediator that could be involved in this process is adenosine, which stimulates a concurrent reduction in cerebral metabolic rate and an increase in cerebral blood flow (CBF). We hypothesized that during the delayed phase after TBI in humans: 1) CSF adenosine concentration is associated with uncoupling of CBF and CMRO2, and 2) adenosine formation is driven by mediator-stimulated cAMP production in injured brain. We serially measured CBF and AVDO2, and CSF adenosine, lactate and cAMP after severe TBI in 13 humans. After 6-18 h, global CBF was increased and AVDO2 was reduced vs all other time periods, defining the uncoupling phase as the period between 18 h and 5 days. CSF adenosine concentration was negatively associated with AVDO2 and strongly associated with death (both p < 0.05), CSF lactate peaked during the initial 18 h, but remained increased for 5 days. CSF cAMP concentration was not increased (vs normal). The association between CSF adenosine concentration and death, and the correlation between uncoupling of CBF and oxidative metabolism and CSF adenosine concentration support our first hypothesis. In contrast, the low levels of cAMP in CSF observed in these patients, but persistently increased CSF lactate, refute our second hypothesis. We speculate that hyperglycolysis or occult ischemic foci are possible sources of ATP breakdown and adenosine formation, and that adenosine is playing a neuroprotective role.

Adenosine↗