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Biomedical subjects

G Fleisher

Publications and source records attributed to G Fleisher.

At least 19 recordsLinked to original sources
PubMed1992

Effect of a human immunoglobulin preparation for intravenous use in a rabbit model of meningococcal endotoxin-induced shock.

BACKGROUND AND METHODS: Endotoxin shock is mediated by various cytokines, including tumor necrosis factor. Treatment of patients with i.v. immunoglobulin has been shown to reduce the concentration of circulating cytokines. The purpose of this study was to determine the protective effects of immunoglobulin for i.v. use on meningococcal endotoxin-induced shock in a rabbit model. Experimental animals were challenged with i.v. meningococcal endotoxin (lipo-oligosaccharide) 10 micrograms/kg, and treated with either a 2-hr i.v. immunoglobulin infusion (400 mg/kg) or a similar saline infusion that was initiated 30 mins before endotoxin challenge. Control animals were challenged with saline alone. RESULTS: Compared with untreated control animals, pulse rate increased (p less than .007) and mean arterial pressure and serum bicarbonate concentrations decreased (p less than .02) in both experimental groups, but did not differ between immunoglobulin-treated and saline-treated animals (p greater than .05) at any time after the endotoxin challenge. Geometric mean serum endotoxin concentrations were significantly (p less than .03) lower in the immunoglobulin-treated animals at 60, 120, 180, 240, 300, and 360 mins after the endotoxin challenge. The geometric mean serum tumor necrosis factor level at 1 hr after the endotoxin challenge in the immunoglobulin-treated experimental animals was lower than in saline-treated animals (5.53 vs. 8.47 tumor necrosis factor enzyme-linked immunosorbent assay U/mL), but not significantly so (p greater than .05). Mortality rate was similar in both experimental groups; eight (67%) of 12 saline-treated experimental rabbits and seven (70%) of ten immunoglobulin-treated rabbits died. All untreated control animals survived 24 hrs. CONCLUSIONS: In this model of circulatory shock in rabbits, i.v. immunoglobulin: a) does not significantly alter the physiologic responses to endotoxin challenge; b) significantly reduces endotoxin concentrations; c) reduces tumor necrosis factor concentrations, but not significantly; and d) does not improve survival rate.

Analysis of Variance↗
PubMed1992

Effect of meningococcal endotoxin in a rabbit model of shock.

Endotoxin in the form of a lipooligosaccharide (LOS) plays a key role in the development of shock in meningococcal sepsis. To examine hemodynamic and biochemical alterations during meningococcal endotoxic shock, we established a rabbit model. Thirty-nine rabbits, weighing 2.5-4.4 kg, were studied. After anesthesia with intramuscular ketamine (20 mg/kg) and xylazine (4 mg/kg), femoral venous and arterial catheters were inserted. Control animals received only saline, while rabbits in each of four additional groups were given LOS in 10-fold increments from 0.1 microgram/kg to 100 microgram/kg. Mean arterial pressure (MAP), heart rate (HR), respirations (RR), temperature (T), urine output, and arterial blood gases (pH, PCO2, PO2, and bicarbonate) were determined at baseline and hourly. Endotoxin levels and TNF levels were measured at 30, 60, 120, 180, 240, 300, and 360 min post-LOS. Survival was recorded. One-way analysis of variance (ANOVA) and the Scheffe procedure, paired samples t-test, two-tailed t-test, and Fisher's exact test were used. Pearson's coefficients were calculated. Animals receiving meningococcal LOS developed tachycardia and compensated metabolic acidosis with an initially normal pH and MAP. With progression of the shock state, the pH decreased and hypotension ensued. Maximal levels of endotoxin were measured 30 min after LOS injection and declined during the ensuing 6 hr. TNF rose from undetectable to markedly elevated levels and peaked at 60-120 min post-LOS. Increasing the amount of injected endotoxin produced more profound degrees of shock until a dose of 10.0 micrograms/kg was reached. There was no correlation between serum TNF at 60 min and survival at 6 hr or 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The spectrum of liver and spleen injuries in children: failure of the pediatric trauma score and clinical signs to predict isolated injuries.

STUDY OBJECTIVES: To determine whether potentially life-threatening intra-abdominal injuries occur in the absence of multisystem trauma in children, and to determine the usefulness of physical examination and a pediatric triage score in the assessment of liver and spleen injuries in children. DESIGN: Retrospective study. SETTING: Admissions to a children's hospital from October 1982 through September 1989 who were found to have liver or spleen injuries. Seventy-seven patients were identified; 55 were male, 22 were female. Mean age was 9 years and 3 months (+/- 56 months) with a range of 22 months to 20 years, 4 months. Clinical signs were recorded and a Pediatric Trauma Score (PTS) and Injury Severity Score (ISS) were calculated for each patient. MEASUREMENTS AND MAIN RESULTS: Fifty-four patients (70%) had a spleen injury, 18 (23%) had a liver injury, and five (7%) had both liver and spleen injuries. Patients were managed without surgery in 63 of 77 cases (82%); two died. Fifty-one of 77 patients (66%) received an ISS of 18 or less; 26 patients (34%) received a score of more than 18. Forty-four of the 51 patients (86%) with an ISS of 18 or less had a normal pulse (120 or less); 48 of the 51 (94%) had a normal systolic blood pressure (90 mm Hg or more). A strong negative correlation (r = -0.80; P = .001) was found between the two scores for children with multiple severe injuries (ISS of more than 18); there was poor correlation (r = -0.04; P greater than .05) between the two scores for isolated liver or spleen injury (ISS of 18 or less). CONCLUSIONS: We conclude that liver or spleen damage may be present in children without other injuries and must be considered with a high index of suspicion, and that neither the initial clinical findings nor the PTS reliably predicts liver or spleen injuries in children with focal abdominal injuries.

Adolescent↗
PubMed1991

Lack of effect of peroral acyclovir for the treatment of acute infectious mononucleosis.

Perorally administered acyclovir was evaluated in the therapy of acute infectious mononucleosis in a multicentered, randomized, double-blind, placebo-controlled trial. A total of 120 patients received 600 mg of acyclovir or placebo five times daily for 10 days. All patients were entered into the study within 7 days of symptom onset and had a positive Monospot test. Analysis of mean values and time to resolution of fever, lymphadenopathy, weight change, hepatomegaly, splenomegaly, liver function tests, atypical lymphocytes, hours of bed rest, sense of well-being, and return to normal activities revealed no significant differences. There was a trend toward suppression of Epstein-Barr virus excretion in the oropharynx in acyclovir recipients. No toxicity was detected in patients treated with acyclovir. Under the conditions of the study, there was no evidence that treatment with perorally administered acyclovir affected the course of infectious mononucleosis.

Acyclovir↗
PubMed1990

Arterial access in the pediatric emergency department.

Arterial catheters are used frequently to monitor critically ill children in ICUs, but their role in the emergency department has not been described. The medical records of all patients admitted to the ICU from the ED of a children's hospital during a 30-month period were reviewed retrospectively. Forty-one patients were identified as having arterial catheters placed in the ED. Catheterization was performed for serial blood gas determinations (59%) or continuous blood pressure monitoring (41%). The radial artery was catheterized in 73% of the 41 patients, and a 22-gauge catheter was used in 78% of the patients. The original catheter was discontinued before the end of medical indication in only 24% of cases--17% were discontinued for failure to draw and 7% for vascular changes at the site of the catheter. We conclude that arterial access can be used for children in the ED to monitor blood pressure and that blood gas tensions and complications are few and generally minor.

Adolescent↗
PubMed1989

Comparison of external jugular and peripheral venous administration of sodium bicarbonate in puppies.

We compared the administration of sodium bicarbonate via a catheter inserted in the external jugular and extending to the junction with the subclavian vein (group 1) and a peripheral hindpaw vein (group 2) in puppies. During spontaneous cardiac activity, the increases in pH (0.12 +/- 0.04 in group 1 vs. 0.08 +/- 0.04 in group 2) and PCO2 (11 +/- 2.8 torr in group 1 vs. 6 +/- 3.2 torr in group 2) in blood from the right atrium 10 sec after the injection of bicarbonate differed significantly. However, the increases in pH (0.31 +/- 0.07 in group 1 vs. 0.30 +/- 0.15 in group 2) and PCO2 (86 +/- 33 torr in group 1 vs. 72 +/- 35 torr in group 2) in blood from the right atrium during closed chest CPR were similar in the two groups. We found that the sodium bicarbonate reached the central circulation more rapidly when administered in the external jugular vein as compared to a peripheral site, but this difference was small and did not reach the level of significance during CPR. Our findings do not provide evidence of any advantage to obtaining central venous access (a potentially complicated procedure) in children with cardiac arrest in regard to the delivery of medications to the heart.

Animals↗
PubMed1989

Prospective evaluation of selective criteria for imaging among children with suspected blunt renal trauma.

The evaluation of children with suspected blunt renal injury relies mainly on clinical assessment, urinalysis, and imaging studies. Because imaging studies rarely influence management, yet entail both risk and expense, we investigated a protocol to define their appropriate use. During a one-year period, children seen in the emergency department underwent a mandated radiographic evaluation for renal injury only if they had (a) severe injuries or (b) a urinalysis with greater than 20 RBC/hpf. Thirty-two children were enrolled; 16 had imaging studies that detected four abnormalities, ie, three contusions and one incidental finding of renal papillary necrosis. All children with abnormal imaging studies had greater than 20 RBC on urinalysis. None of the 16 children who were not studied radiographically developed complications related to renal trauma during short-term follow-up. Our findings support earlier recommendations for limiting the use of imaging for suspected blunt renal trauma in children with minor to moderate injuries and hematuria of less than or equal to 20 RBC/hpf.

Adolescent↗
PubMed1987

Antibiotic administration to treat possible occult bacteremia in febrile children.

We performed a prospective, randomized, placebo-controlled, double-blind clinical trial of antibiotic administration to treat possible occult bacteremia in febrile children. A total of 955 children aged 3 to 36 months with temperatures greater than or equal to 39.0 degrees C and no focal bacterial infection were enrolled at the emergency departments of two children's hospitals from January 1982 until July 1984. Blood samples for culture were obtained, and the children were randomly assigned to receive either oral amoxicillin or placebo and were restudied approximately 48 hours after enrollment. Data were also collected on 228 children who could not be randomly assigned. Twenty-seven of the randomly assigned children (2.8 percent) had bacteremic infections with pathogenic organisms (Streptococcus pneumoniae, Haemophilus influenzae, and salmonella). There were no differences in the incidence of major infectious morbidity associated with bacteremia between the antibiotic and placebo groups--2 of 19 patients (10.5 percent) in the antibiotic group and 1 of 8 (12.5 percent) in the placebo group--although the power for this comparison was low. Antibiotics reduced fever (P less than 0.005) and improved the clinical appearance (P = 0.07) in the children with bacteremia but not in those without bacteremia. Although there were no statistically significant differences in the incidence of side effects, diarrhea tended to occur more often in the patients treated with amoxicillin (15 vs. 11 percent, P less than 0.10). We conclude that our data do not support the routine use of standard oral doses of amoxicillin in febrile children who do not have evidence of focal bacterial disease.

Amoxicillin↗
PubMed1987

Fluid resuscitation following liver laceration: a comparison of fluid delivery above and below the diaphragm in a pediatric animal model.

Liver laceration is the most common cause of mortality following blunt abdominal trauma in children. To determine the optimal route for volume expansion in the clinical setting of blunt abdominal injury, we compared the response to fluid resuscitation delivered above (Group 1) or below (Group 2) the diaphragm in a canine model of liver laceration. After induction of hemorrhagic shock by resection of 45% to 55% of the right median hepatic lobe followed by immediate closure of the laparotomy incision, we monitored pulse, arterial and venous pressures, urine output, pH, and lactate levels for three hours or until death. Physiologic and biochemical parameters did not differ significantly between the two groups; three of six (50%) of those receiving fluids through the external jugular vein and four of seven (57%) resuscitated through the femoral vein survived for three hours. Comparing survivors and nonsurvivors in both groups, those animals that lived for three hours maintained a higher pH, a greater urine output, and a lower serum lactate level. We conclude that the route of IV fluid administration does not affect the response to volume expansion; lactate levels, urine output, and pH provide valuable guides to the adequacy of resuscitation; and in appropriately resuscitated patients, even with serious liver lacerations, operative repair may be unnecessary except in the face of clinical or biochemical deterioration despite optimal fluid and blood replacement.

Animals↗
PubMed1987

Intraosseous infusion flow rates in hypovolemic "pediatric" dogs.

We tested a 20-gauge, 2 1/2-inch spinal needle and a 13-gauge, 3 1/2-inch bone marrow needle with Ringer's lactate delivered by gravity and 300 mm Hg pressure in vitro and in hypovolemic puppies to ascertain in vivo intraosseous flow rates and to determine the effects of catheter size and anatomic factors on flow rate. In vitro flow was significantly faster than in vivo flow (P = .001). In vivo, mean flow rates were 11 mL/min for the 20-gauge needle and 13 mL/min for the 13-gauge needle by gravity. The mean flows by 300 mm Hg pressure for the same needles were 24 mL/min and 29 mL/min. While the in vivo flow rates were significantly greater for the 13-gauge versus the 20-gauge needle, the differences were not clinically significant (2 mL/min difference by gravity and 5 mL/min difference by pressure). The clinically comparable in vivo rates for the two needles tested indicated that the rates are dependent on flow through the bone marrow rather than the size of the needle. The data suggest that while intraosseous infusion is a rapid technique for gaining vascular access, the flow rates achieved may not be sufficient for the definitive treatment of severe hypovolemic or hemorrhagic shock alone.

Animals↗
PubMed1987

Slow versus rapid closed-chest cardiac compression during cardiopulmonary resuscitation in puppies.

The recommended rates for closed-chest cardiac compressions during CPR are based on physiologic variations with increasing age rather than experimental data. Using puppies, we compared mean arterial pressure, cardiac index (CI), and cerebral blood flow (CBF) at a slow (40/min, group 1) and a rapid (120/min, group 2) rate. CBF was measured in all experiments by N2O uptake before and during CPR from cardiac arrest induced with KCl. Both CI and CBF were measured in half of the subjects with radiolabeled microspheres. Groups 1 and 2 were similar in terms of baseline mean weight, mean arterial pressure, CI, CBF, and arterial and venous blood gases. During resuscitation for group 1, the mean CI was 221 ml/min . m2, and the mean CBF was 4 ml/100 g . min determined by N2O uptake (2 ml/100 g.min by microspheres); in group 2, the respective means were 248 ml/min . m2 and 4 ml/100 g . min with both techniques. The values for mean CI and CBF (N2O or microspheres) did not differ significantly at either rate of compression. The N2O uptake and microsphere techniques for measuring CBF correlated closely during spontaneous cardiac contractions and mechanical chest compressions. We conclude that a) closed-chest cardiac compressions at either rate studied provided inadequate CBF, and b) the N2O uptake and microsphere techniques give similar measures of CBF under conditions of normal and low flow.

Animals↗
PubMed1986

Central and peripheral catheter flow rates in "pediatric" dogs.

Several authors have reported flow rates for various catheters in vitro, but these studies may not reflect differences in vivo because of intravascular pressure, valves, and/or venous tortuosity, particularly in the small vessels of the child. We studied flow rates of four small-gauge catheters in a "pediatric" dog model. We found that flow rates were less in vivo than in vitro, less in peripheral than in central veins, and equal in hypovolemic and normovolemic dogs. Our data indicate that the results of in vitro studies cannot be extrapolated directly to predict achievable flow rates in clinical practice. In particular, a small-diameter catheter in the central circulation may allow delivery of fluid under pressure at a faster rate than does a catheter of larger diameter in a peripheral vein. Thus decisions about site, type, and size of catheter for fluid resuscitation should be based on data obtained in vivo.

Animals↗
PubMed1986

Effect of dichloroacetate in the treatment of anoxic lactic acidosis in dogs.

Lactic acidosis is seen frequently after severe anoxia and circulatory failure. Because dichloroacetate (DCA) has been shown to be effective in the treatment of lactic acidosis, we studied its effect on lactate levels and pH in arterial and sagittal sinus blood specimens in a pediatric canine model of anoxic cardiac arrest followed by CPR. Lactate levels rose steadily in all puppies receiving DCA alone (group 1), DCA plus bicarbonate (group 2), bicarbonate alone (group 3), or neither drug (group 4). Arterial and sagittal-sinus lactate levels were in the range of 2 mmol/L during the baseline period, 6 mmol/L after anoxic arrest, and 10 mmol/L after 20 min of CPR. Bicarbonate, but not DCA, significantly raised arterial pH. Neither drug reversed the progression of acidosis in the sagittal sinus; mean pH ranged from 6.85 to 6.92 among the four groups after 20 min of CPR. We speculate that DCA did not decrease lactate levels or raise the pH in either the peripheral circulation or the CNS (sagittal sinus) because of poor perfusion achieved during closed-chest cardiac compression.

Acetates↗
PubMed1985

Open- versus closed-chest cardiac compressions in a canine model of pediatric cardiopulmonary resuscitation.

Whether or not the principles of adult resuscitation apply to the pediatric population remains unknown. In order to study this issue, a pediatric animal model was developed using puppies 6-12 weeks of age and 2-8 kg in weight. Hemodynamic status was assessed using standard methods, and measured global cerebral blood flow was assessed using the nitrous oxide (Kety-Schmidt) technique after placement of a catheter in the sagittal sinus. In this initial study, five puppies resuscitated with closed-chest cardiac compression (CCCC) were compared with five receiving open-chest cardiac compression (OCCC). Although mean systolic arterial pressures were equal with both methods during resuscitation (40 versus 49 mm Hg, P = 0.19), OCCC produced a greater cardiac output and a higher cerebral blood flow (5 versus 18 ml/100 g/min, P = 0.008). Only one of five dogs treated with CCCC had a blood flow during resuscitation greater than 15 ml/100 g/min, as compared with four of five receiving OCCC. Finally, three of five dogs in the CCCC group experienced liver lacerations, while none who were resuscitated by OCCC sustained any gross visceral injuries.

Animals↗