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Biomedical subjects

S B Rizoli

Publications and source records attributed to S B Rizoli.

At least 19 recordsLinked to original sources

Advances in fluid resuscitation of hemorrhagic shock.

The optimal fluid for resuscitation in hemorrhagic shock would combine the volume expansion and oxygen-carrying capacity of blood without the need for cross-matching or the risk of disease transmission. Although the ideal fluid has yet to be discovered, current options are discussed in this review, including crystalloids, colloids, blood and blood substitutes. The future role of blood substitutes is not yet defined, but the potential advantages in trauma or elective surgery may prove to be enormous.

Blood Substitutes↗

In vivo and in vitro modulation of intercellular adhesion molecule (ICAM)-1 expression by hypertonicity.

Hepatic ischemia-reperfusion (I/R) is an important cause of organ dysfunction in the critically ill. With reperfusion, Kupffer cells release pro-inflammatory cytokines that promote endothelial cell (EC) expression of adhesion molecules such as intercellular adhesion molecule (ICAM)-1, facilitating neutrophil (PMN) infiltration. Studies suggest hypertonic saline (HTS) might exert beneficial effects on development of organ injury following shock on the basis of reduced PMN-EC interactions. We hypothesized that HTS alters expression of EC ICAM-1 and thus minimizes PMN-mediated injury. To test our hypothesis, we used an in vivo model of hepatic I/R and an in vitro model of activated EC. Rats underwent 30 min of hepatic ischemia after pretreatment with HTS (7.5% NaCl, 4cc/kg ia) or normal saline (NS). At 4 h reperfusion, plasma was taken for aspartate aminotransferase (AST) and liver tissue was harvested for assessment of hepatic ICAM-1 mRNA by Northern blot analysis. Human umbilical vein endothelial cells (HUVECs) were activated by lipopolysaccharide (LPS) and exposed to hypertonic medium (350-500 mOsM). HUVEC ICAM-1 protein was measured by cell ELISA and ICAM-1 mRNA by Northern blot analysis. HTS prevented hepatic I/R injury as measured by AST. AST of shams was 282.6+/-38.1 IU/L. I/R following NS pretreatment caused significant injury (AST 973.8+/-110.9 IU/L) compared to sham (SM) (P < 0.001). Pretreatment with HTS exerted significant protection following I/R with an AST of 450.9+/-56.3 IU/L (P < 0.05). There was no significant difference in AST levels between SM and HTS groups. Reduced hepatic injury after HTS and I/R was accompanied by inhibition of I/R-induced hepatic ICAM-1 mRNA expression compared to NS treated animals (P < 0.01). Similarly, hypertonicity inhibited HUVEC LPS-induced ICAM-1 protein (LPS: 1.86+/-0.19 absorbance units; 400 mOsM +/- LPS: 1.45+/-0.14 absorbance units; 450 mOsM + LPS: 1.02+/-0.19 absorbance units, P < 0.001) and mRNA expression. Thus, hypertonicity modulates endothelial ICAM-1 expression as one possible protective mechanism against I/R injury.

Animals↗

Hypertonic inhibition of exocytosis in neutrophils: central role for osmotic actin skeleton remodeling.

Hypertonicity suppresses neutrophil functions by unknown mechanisms. We investigated whether osmotically induced cytoskeletal changes might be related to the hypertonic inhibition of exocytosis. Hyperosmolarity abrogated the mobilization of all four granule types induced by diverse stimuli, suggesting that it blocks the process of exocytosis itself rather than individual signaling pathways. Concomitantly, osmotic stress provoked a twofold increase in F-actin, induced the formation of a submembranous F-actin ring, and abolished depolymerization that normally follows agonist-induced actin assembly. Several observations suggest a causal relationship between actin polymerization and inhibition of exocytosis: 1) prestimulus actin levels were inversely proportional to the stimulus-induced degranulation, 2) latrunculin B (LB) prevented the osmotic actin response and restored exocytosis, and 3) actin polymerization induced by jasplakinolide inhibited exocytosis under isotonic conditions. The shrinkage-induced tyrosine phosphorylation and the activation of the Na(+)/H(+) exchanger were not affected by LB. Inhibition of osmosensitive kinases failed to prevent the F-actin change, suggesting that the osmotic tyrosine phosphorylation and actin polymerization are independent phenomena. Thus cytoskeletal remodeling appears to be a key component in the neutrophil-suppressive, anti-inflammatory effects of hypertonicity.

Actins↗

Cell volume-dependent regulation of L-selectin shedding in neutrophils. A role for p38 mitogen-activated protein kinase.

Neutrophil-mediated organ damage is a common feature of many disease states. We previously demonstrated that resuscitation with hypertonic salt solutions prevented the endotoxin-induced leukosequestration and consequent lung injury, and this effect was partially attributed to an altered surface expression of adhesion molecules, CD11b and L-selectin. In this study we investigated the mechanisms whereby osmotic stress evokes L-selectin shedding. The metalloprotease inhibitor RO 31-9790 prevented the osmotic down-regulation of L-selectin, indicating that this process was catalyzed by the same "sheddase" responsible for L-selectin cleavage induced by diverse inflammatory stimuli. The trigger for hypertonic shedding was cell shrinkage and not increased osmolarity, ionic strength, or intracellular pH. Volume reduction caused robust tyrosine phosphorylation and its inhibition by genistein and erbstatin abrogated shedding. Shrinkage stimulated tyrosine kinases Hck, Syk, and Pyk2, but prevention of their activation by the Src-family inhibitor PP1 failed to affect the L-selectin response. Hypertonicity elicited the Src family-independent activation of p38, and the inhibition of this kinase by SB203580 strongly reduced shedding. p38 was also essential for the N-formyl-methionyl-leucyl-phenylalanine- and lipopolysaccharide-induced shedding but not the phorbol ester-induced shedding. Thus, cell volume regulates L-selectin surface expression in a p38-mediated, metalloprotease-dependent manner. Moreover, p38 has a central role in shedding induced by many inflammatory mediators.

Calcium-Calmodulin-Dependent Protein Kinases↗

Hypertonic immunomodulation is reversible and accompanied by changes in CD11b expression.

BACKGROUND: In a two-hit model of hemorrhagic shock and lipopolysaccharide (LPS), we previously showed that hypertonic saline (HTS) resuscitation reduced lung sequestration of neutrophils and the accompanying injury. This effect was partially attributed to suppressed expression of the surface adhesion molecule CD11b. This study investigates the duration of this protective effect after a single HTS dose and the usefulness of repeated infusions. MATERIAL AND METHODS: The previous two-hit rodent model was used. Neutrophil lung sequestration was measured by bronchoalveolar fluid cell count. CD11b expression was followed by flow cytometry. In vitro studies used isolated human neutrophils. RESULTS: Eighteen hours following resuscitation, the protective effect of HTS was lost. At this time, LPS caused an increase in both neutrophil lung sequestration and CD11b expression, regardless of the resuscitation regimen used. A second infusion of HTS prevented these changes and restored the lung protection observed earlier. In vitro studies showed that the duration of hypertonic pretreatment is an important determinant of cell responsiveness under the isotonic conditions: Four but not 2 h hypertonic exposure was able to prevent upregulation of CD11b induced by LPS added immediately after reestablishing isotonicity. CONCLUSIONS: This study demonstrates that HTS resuscitation lessens lung neutrophil sequestration and CD11b surface expression induced by LPS. This protective effect is transient but can be restored by a second HTS infusion suggesting that maintenance of beneficial effect necessitates repeated HTS addition. The reversibility ensures rapid modulation of neutrophil functions, thereby preventing acute tissue damage without causing long-lasting immunosuppression.

Animals↗

Hypertonicity prevents lipopolysaccharide-stimulated CD11b/CD18 expression in human neutrophils in vitro: role for p38 inhibition.

BACKGROUND: Neutrophil sequestration in the lungs plays an important role in the development of acute respiratory distress syndrome. We previously reported that hypertonic saline resuscitation attenuated lung injury after hemorrhagic shock and lipopolysaccharide (LPS) by abolishing neutrophil CD11b up-regulation. We investigated the mechanism underlying this effect. METHODS: Human neutrophils were exposed to LPS in the presence or absence of hypertonicity or SB203580 (p38 inhibitor). CD11b and CD14 were studied by immunofluorescence and p38 phosphorylation by immunoblotting. RESULTS: Hypertonicity had no effect on CD11b or CD14, caused a weak p38 phosphorylation, and completely prevented the LPS-induced p38 phosphorylation and CD11b up-regulation. p38 inhibition also abrogated CD11b up-regulation by LPS. CONCLUSION: MAPKp38 is important in CD11b regulation by LPS. The inhibitory effect of hypertonicity on the LPS-mediated effect may contribute to its protective anti-inflammatory effect observed in vivo. Transient hypertonicity might minimize organ injury in diseases characterized by neutrophil-mediated damage such as ARDS.

Blotting, Western↗

Immunomodulatory effects of hypertonic resuscitation on the development of lung inflammation following hemorrhagic shock.

Hypertonic resuscitation fluids are known to be effective in restoring circulating volume in the hypovolemic trauma patient. Previous studies have suggested that hypertonicity might exert effects on immune cells leading to an altered host response. The present studies evaluated the effect of hypertonic resuscitation on the development of lung injury in a hemorrhagic shock model in which antecedent shock primes for increased lung neutrophil sequestration in response to intratracheal LPS. Resuscitation with hypertonic saline significantly reduced albumin leak, bronchoalveolar lavage fluid neutrophil counts, and the degree of histopathologic injury compared with resuscitation with Ringer's lactate. Both in vivo and in vitro data suggest that this beneficial effect may be related to altered adhesion molecule expression by the neutrophil. Specifically, hypertonicity induced shedding of L-selectin and prevented LPS-stimulated expression and activation of CD11b, both of which might contribute to reduced sequestration in the lung. Impaired up-regulation of lung ICAM-1 may have also participated, although ex vivo studies suggest that alterations in neutrophils were sufficient to account for the effect. Lung cytokine-induced neutrophil chemoattractant did not differ between animals resuscitated with hypertonic saline vs Ringer's lactate. Considered together, these studies demonstrate a possible novel approach to inhibiting organ injury in disease processes characterized by neutrophil-mediated damage.

Adjuvants, Immunologic↗

Emergent abdominal sonography as a screening test in a new diagnostic algorithm for blunt trauma.

Although there is an interest in emergent abdominal sonography (EAS), the clinical utilization of EAS in North America is minimal. The purpose of this study was to develop a new diagnostic algorithm for blunt abdominal injury based on a prospective blinded comparison of EAS, diagnostic peritoneal lavage (DPL), and computed tomography (CT). EAS (+ = fluid, - = no fluid) was performed before the DPL or CT, in 400 patients with a mean Injury Severity Score of 26; 293 had a CT and 107 had a DPL. The EASs required 2.6 +/- 1.2 minutes with 82% < or = 3 minutes. The accuracy of EAS for free fluid was 94% with a positive and negative predictive value of 82 and 96%, respectively. Only 1 of 338 patients with EAS- had an acute therapeutic laparotomy. Three patients with EAS- had a delayed laparotomy based on evolving clinical findings. The radiologists interpretation of the EAS video disagreed with the clinician sonographer in only 3% of cases. Based on these results, a diagnostic algorithm was developed using EAS as a screening test with selective use of DPL and CT. Emergent abdominal sonography performed by clinician sonographers is a rapid and accurate test for peritoneal fluid in blunt trauma victims, and the need for laparotomy in patients with a negative EAS is rare. Our study supports the routine use of EAS as a screening test in a diagnostic algorithm for the evaluation of blunt abdominal trauma.

Abdominal Injuries↗

Injury pattern and severity in lateral motor vehicle collisions: a Canadian experience.

OBJECTIVE: To determine the pattern and severity of injury and the outcome of front seat motor vehicle occupants after lateral impact crashes. DESIGN: Retrospective review undertaken in a Regional Trauma Unit (Sunnybrook Health Science Centre). MATERIALS AND METHODS: Review of seriously injured front seat motor vehicle occupants admitted to a Regional Trauma Unit over a 46-month period (September 15, 1989, to July 15, 1993) for whom vehicle crash information and occupant seat belt use were known. MEASUREMENTS AND MAIN RESULTS: Three hundred forty-eight front seat vehicle occupants were available for study; one hundred forty-one (41%) were involved in a lateral impact motor vehicle crash. Driver side lateral crashes (57%) were more common than passenger side impacts. Victims of lateral impact crashes had a significantly higher mean Injury Severity Score (25 compared with 20 for nonlateral crashes: p < 0.05), and the direction of impact was strongly associated with injury severity (p < 0.05). Lateral impact crashes resulted in substantially more significant chest (p < 0.01) and intra-abdominal (p < 0.0001) injuries. Type of injury was significantly different between the lateral and nonlateral impact groups for facial, chest, abdominal, and musculoskeletal injuries. CONCLUSIONS: The direction of impact in motor vehicle crashes is strongly associated with the pattern and severity of organ injuries. Further attention to automobile safety design is necessary to better protect occupants involved in lateral impact crashes.

Accidents, Traffic↗

Hypotension after blunt abdominal trauma: the role of emergent abdominal sonography in surgical triage.

OBJECTIVE: Trauma victims with hypotension require a rapid and reliable localization of bleeding and expedient surgical triage. Our hypothesis is that emergent abdominal sonography (EAS) is a rapid and accurate test of the need for urgent laparotomy in blunt trauma victims with hypotension. METHODS: Among 400 blunt trauma victims entered in a prospective blind study of EAS, a subgroup of 69 (17%) patients had a systolic blood pressure < or = 90 mm Hg during their initial assessment. Although the EAS results [(+) = fluid, (-) = no fluid] were not used in clinical decision making, the potential contribution of EAS to patient care was examined. RESULTS: The mean Injury Severity Score was 32. Twenty-two (32%) patients were EAS (+), of which 19 required an acute laparotomy. No laparotomies were performed in the 47 EAS (-) patients. The EASs required 19 +/- 5 seconds in the EAS (+) group and 154 +/- 13 seconds in the EAS (-) group. Twenty of the 22 positive EASs had free fluid in Morison's pouch. All 13 patients with an ultrasound score > or = 3 had a laparotomy. The primary etiology of hypotension was blood loss in 42 patients, hemoperitoneum in 18, and retroperitoneal hemorrhage in 12. CONCLUSION: EAS is a rapid and accurate indicator of the need for urgent laparotomy in the hypotensive blunt trauma victim. Further, a negative EAS can hasten the search for other causes of hypotension. Diagnostic peritoneal lavage may become obsolete in centers with EAS capabilities.

Abdominal Injuries↗

Classification of liver trauma.

The classification of liver injuries is important for clinical practice, clinical research and quality assurance activities. The Organ Injury Scaling (OIS) Committee of the American Association for the Surgery of Trauma proposed the OIS for liver trauma in 1989. The purpose of the present study was to apply this scale to a cohort of liver trauma patients managed at a single Canadian trauma centre from January 1987 to June 1992. 170 study patients were identified and reviewed. The mean age was 30, with 69% male and a mean ISS of 33. 90% had a blunt mechanism of injury. The 170 patients were categorized into the 6 OIS grades of liver injury. The number of units of blood transfused, the magnitude of the operative treatment required, the liver-related complications and the liver-related mortality correlated well with the OIS grade. The OIS grade was unable to predict the need for laparotomy or the length of stay in hospital. We conclude that the OIS is a useful, practical and important tool for the categorization of liver injuries, and it may prove to be the universally accepted classification scheme in liver trauma.

Adolescent↗

Post-traumatic small-bowel stricture: a case report.

The use of lap seat belts has recently been recognized as a mechanism of blunt injury to the small bowel. Patients usually present immediately after injury and require urgent laparotomy. An unusual case of delayed small-bowel stricture after conservative management of an injury resulting from blunt trauma is reported. A 37-year-old woman involved in a high-speed motor vehicle accident was managed in hospital by observation. She had abdominal distension and pain, which gradually decreased and allowed slow introduction of a liquid diet. She was discharged from hospital but returned 6 weeks after injury with pain, abdominal distension, vomiting and obstipation. Stricture of an 8-cm segment of distal jejunum was found. Resection of the involved segment with primary anastomosis was curative.

Adult↗

Insertion of a transpyloric feeding tube during laparotomy in the critically injured: rationale and plea for routine use.

Although clinical and experimental evidence favours early enteral feeding in the critically injured, provision of such enteral feeds can be difficult. Gastric feeds are often not tolerated and may lead to aspiration. An intolerance of gastric feeds leads to a cumulative energy and protein deficit and may result in the initiation of expensive parenteral nutrition (TPN). An alternative and under-utilized technique to ensure enteral access in trauma victims is the insertion of a transpyloric (nasojejunal) feeding tube during emergent laparotomy. We have employed this method of enteral access with success. In the following report, we describe this technique, provide an illustrative case with a cost comparison between nasojejunal feeds and TPN, present the rationale for such a mode of enteral access and outline the indications and contraindications. Enteral access by the intra-operative insertion of a transpyloric feeding tube allows immediate/early enteral feeding that is easy, safe, reliable and inexpensive.

Adult↗

A prospective study of emergent abdominal sonography after blunt trauma.

In North America, the role of emergent abdominal sonography [ultrasonography (US)] after blunt trauma requires further definition. The purpose of this prospective study was to compare US to the gold standards, diagnostic peritoneal lavage (DPL), and computed tomography (CT), in a population of adults after blunt trauma. In 206 adults who required either CT or DPL to assess possible abdominal injury, US was performed, before DPL or CT, and was aimed at the detection of intraperitoneal fluid. The mean Injury Severity Score and Glasgow Coma Scale score were 24.0 and 11.9, respectively. One hundred thirty-seven patients (67%) had CT and 69 (33%) had DPL. The positive and negative predictive values of US for intraperitoneal fluid were 90% and 97%, respectively. The sensitivity, specificity, and accuracy of US for free fluid were 81%, 98%, and 96%, respectively. Of the six false-negative USs, only one required surgery. The US examinations required 2.6 +/- 1.4 min. Emergent abdominal sonography is an accurate, rapid test for the presence of intraperitoneal fluid in adult blunt trauma victims and in these patients may prove valuable as a screening test for abdominal injury.

Abdominal Injuries↗

Injuries missed during initial assessment of blunt trauma patients.

OBJECTIVE: To determine the incidence and clinical significance of undiagnosed injuries in blunt trauma patients at our institution. DESIGN: Retrospective analysis of blunt trauma admissions over a 1-year period. Missed injury (MI) was defined as any injury recorded after the initial 24 hours. RESULTS: Of 432 patients studied, 59 (13.6%) had MI. Fractures were the most common MI. Thirty-five percent of MI were detected during repeated physical examination and 28% after patients were conscious and able to voice concerns. CONCLUSION: Over 10% of all blunt trauma patients had undiagnosed injuries. Forty percent of the MI had clinical implications. The most effective method of diagnosis consists of repeated clinical assessments. Special attention should be focused on patients with severe anatomical injuries, obtunded or intubated.

Adult↗

Blunt diaphragmatic and thoracic aortic rupture: an emerging injury complex.

Although both blunt diaphragmatic rupture (BDR) and thoracic aortic rupture (TAR) have been extensively discussed, the association of both injuries has been infrequently mentioned. The purpose of this study was to examine the current prevalence and clinical characteristics of combined BDR and TAR at an adult regional trauma unit. Among 3,886 trauma victims, 69 (1.8%) had a BDR and 44 (1.1%), a TAR. Seven patients (10% of all patients with a BDR) had both injuries. All 7 were victims of motor vehicle crashes and had a mean Injury Severity Score of 35. All TARs were just distal to the origin of the left subclavian artery. Five patients underwent repair of both injuries and survived, 1 patient had only the BDR repaired and survived, and 1 died during emergency thoracotomy, for a survival rate of 86%. Five patients had laparotomy and repair of the BDR in the presence of an unrepaired TAR. The TARs were repaired by the clamp-and-sew technique, three of them with primary repair and two with interposition tube grafts. Concomitant BDR and TAR appears to be an emerging injury complex with both diagnostic and therapeutic challenges. The presence of BDR demands a rigorous search for associated TAR.

Adolescent↗

What are the clinical determinants of early energy expenditure in critically injured adults?

The clinical determinants of energy expenditure in critically injured adults require definition. Among adult blunt trauma victims who required mechanical ventilation, the resting energy expenditure was calculated with the Harris-Benedict equation (HBEE) and the early (< or = 5 days postinjury) energy expenditure was measured by indirect calorimetry (MEE) (n = 115). The MEE was 2052 +/- 531 kcal/day and MEE/HBEE ("stress factor") was 1.24 +/- 0.2. The MEE was correlated with HBEE, age, height, weight, sex, temperature, and paralytic agents (p < 0.01). However, MEE did not correlate with ISS, admission GCS score, admission base deficit, initial systolic blood pressure, or the number of units of packed red blood cells transfused in the first 24 hours after injury (p = NS). Temperature and paralysis correlated with MEE/HBEE (p < 0.01). A regression model of MEE was developed with the clinical variables HBEE, temperature, and the presence or absence of paralytic agents (r2 = 0.62; p < 0.001): MEE (kcal/d) = 1.4(HBEE) + 71.4(temperature) + 274(paralytics; + = 1, - = 2) - 3485. In mechanically ventilated trauma victims, both the early energy expenditure and the stress factor are determined by host factors but are independent of the severity of the anatomic and physiologic insult. The degree of hypermetabolism observed in this population was less than previously reported.

Adult↗