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Biomedical subjects

S M Cohn

Publications and source records attributed to S M Cohn.

At least 37 records · Page 2Linked to original sources
PubMed2000

Pharmacokinetics and burn eschar penetration of intravenous ciprofloxacin in patients with major thermal injuries.

Adequate penetration of antibiotics into burn tissue and maintenance of effective serum levels are essential for the treatment of patients sustaining major thermal injuries. The pharmacokinetics and burn eschar penetration of intravenous ciprofloxacin were determined in 12 critically ill patients with burn injuries. Mean age for the 12 patients was 45 +/- 17 (range 25-82 years), total body surface area burned (TBSAB) = 38 +/- 15% and Acute Physiology and Chronic Health Evaluation (APACHE) II score = 8 +/- 6. Patients received recommended doses of ciprofloxacin, 400 mg q12h iv, for three doses beginning 72 h post-burn. Serum concentrations were measured at t = 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 4.0 and 12.0 h after the first and third doses. Burn eschar biopsies were obtained after the third ciprofloxacin dose. Three of these 12 patients (25%) manifested later signs of clinical sepsis (TBSAB = 61 +/- 6% and APACHE II score = 11 +/- 3) and underwent a second infusion of three doses of intravenous ciprofloxacin, blood sampling and eschar biopsy. Serum and eschar concentrations were determined by high performance liquid chromatography. Serum ciprofloxacin concentrations were comparable to those of normal volunteers (C(max) = 4.0 +/- 1 mg/L and AUC = 11.4 +/- 2 mg.h/L) during the immediate post-burn period after dose 1 (C(max1) = 4.8 +/- 3 mg/L and AUC(0-12) = 12.5 +/- 7 mg. h/L) and dose 3 (C(max3) = 4.9 +/- 2 mg/L and AUC(24-36) = 17.5 +/- 11 mg.h/L). Mean burn eschar concentration during the 72 h post-burn was significantly lower than that found during clinical sepsis (18 +/- 17 compared with 41.3 +/- 54 microg/g; P < 0.05 by t test). Similar serum concentrations were achieved in patients with clinical sepsis (C(max1) = 4.2 +/- 0.2 mg/L and AUC(0-12) = 15.0 +/- 3 mg. h/L; C(max3) = 5.0 +/- 1 mg/L and AUC(24-36) = 22.8 +/- 9 mg.h/L). A positive correlation between burn eschar concentrations and C(max) (r = 0.71, r(2) = 0.51, P = 0.01) was found by linear regression analysis. A C(max)/MIC ratio > 10 (MIC = 0.5 mg/L) and an AUC/MIC ratio > 100 SIT(-1).h (serum inhibitory titre) (MIC = 0.125 mg/L) were achieved. High burn eschar concentrations and serum levels, similar to those found in normal volunteers, can be achieved after intravenous ciprofloxacin infusion in critically ill burns patients.

Adult↗
PubMed2000

Comparison of intravenous/oral ciprofloxacin plus metronidazole versus piperacillin/tazobactam in the treatment of complicated intraabdominal infections.

OBJECTIVE: To compare the safety and efficacy of intravenous (IV) ciprofloxacin plus IV metronidazole (CIP+MET) with that of IV piperacillin/tazobactam (PIP/TAZO) in adults with complicated intraabdominal infections, and to compare the efficacy of sequential IV-to-oral CIP+MET therapy with that of the IV CIP-only regimen. SUMMARY BACKGROUND DATA: Treatment of intraabdominal infections remains a challenge, mainly because of their polymicrobial etiology and attendant death and complications. Antimicrobial regimens using sequential IV-to-oral therapy may reduce the length of hospital stay. METHODS: In this multicenter, randomized, double-blind trial involving 459 patients, clinically improved IV-treated patients were switched to oral therapy after 48 hours. Overall clinical response was the primary efficacy measurement. RESULTS: A total of 282 patients (151 CIP+MET, 131 PIP/TAZO) were valid for efficacy. Of these patients, 64% CIP+MET and 57% PIP/TAZO patients were considered candidates for oral therapy. Patients had a mean APACHE II score of 9.6. The most common diagnoses were appendicitis (33%), other intraabdominal infection (29%), and abscess (25%). Overall clinical resolution rates were statistically superior for CIP+MET (74%) compared with PIP/TAZO (63%). Corresponding rates in the subgroup suitable for oral therapy were 85% for CIP+MET and 70% for PIP/TAZO. Postsurgical wound infection rates were significantly lower in CIP+MET (11%) versus PIP/TAZO patients (19%). Mean length of stay was 14 days for CIP+MET and 17 days for PIP/TAZO patients. CONCLUSION: CIP+MET, initially administered IV and followed by CIP+MET oral therapy, was clinically more effective than IV PIP/TAZO for the treatment of patients with complicated intraabdominal infections.

Abdomen↗
PubMed2000

Utility of near-infrared spectroscopy in the diagnosis of lower extremity compartment syndrome.

OBJECTIVE: To determine the utility of near-infrared spectroscopy in the diagnosis of lower extremity compartment syndrome (CS). METHODS: Nine patients with CS confirmed by physical examination and elevated compartment pressures (64 +/- 17 mm Hg) were evaluated before and after fasciotomy. Control readings were also performed on 33 surgical patients who had no evidence of CS. The deltoid muscle was used as a reference value. RESULTS: The deltoid muscle oxygen saturation (StO2) readings revealed a mean = 84 +/- 17% prefasciotomy and mean = 83 +/- 12% postfasciotomy in the CS group. The control group had a mean StO2 of 83 +/- 11%. In the CS group, the leg compartment with the highest pressure had a StO2 mean = 56 +/- 27% before fasciotomy. This value was statistically significantly lower (p < 0.05) than either the postfasciotomy mean StO2 in that compartment (82 +/- 16%) or the values found in matched control patients with no evidence of CS (87 +/- 7%). CONCLUSION: Near-infrared spectroscopy-derived StO2 values in the lower extremities of trauma patients with CS were diminished relative to the control patients and usually normalized after fasciotomy. Near-infrared spectroscopy evaluation may offer a rapid, noninvasive method of assessing extremities at risk for CS.

Adult↗
PubMed2000

Identification of trauma patients at risk of thoracic aortic tear by mechanism of injury.

OBJECTIVE: We sought to identify potential measurable on-scene information that would assist clinicians in the identification of patients at risk for thoracic aortic tear (AT) after vehicular trauma. METHODS: Data were prospectively collected at the scene of 295 motor vehicle crashes from 1995 to 1999. There were 34 cases (12%) with AT. Scene data consisted of vehicle maximal crush, maximal intrusion into the occupant compartment, change in velocity (Delta V) and principal direction of force. Thoracic aortic injuries were confirmed radiographically or at autopsy. Crash factors were analyzed for correlation with AT by logistic regression. RESULTS: Delta V > or = 20 mph and near-side impact were the factors having the strongest correlation with thoracic aortic injury. Delta V > or = 20 mph (n = 32 with AT) had an odds ratio = 6.4, (p < 0.01). Near impact (n = 20 with AT) had an odds ratio = 2.3, (p < 0.05) and intrusion > or = 15 inches had an odds ratio = 3.2, p < 0.05. The sensitivity, specificity, and accuracy of the presence of near impact, Delta V > or = 20 mph, or both, were 100%, 34%, and 64%. The positive and negative predictive values were 16% and 100%, respectively. There was no relationship of AT to use of seat belts or airbags. CONCLUSION: Thoracic aortic injury after vehicular collision can be reliably excluded if near-impact, Delta V > or = 20 mph, or intrusion > or = 15 inches are not present. Mechanism of injury in the form of crash scene information may aid clinicians in identifying individuals at risk for thoracic aortic tear after vehicular trauma.

Accidents, Traffic↗
PubMed2000

Incidence and susceptibility of pathogenic bacteria vary between intensive care units within a single hospital: implications for empiric antibiotic strategies.

BACKGROUND: The purpose of this study was to determine whether the incidence of recovery and patterns of antibiotic susceptibility of pathogenic bacteria vary between intensive care units (ICUs) in a single teaching hospital. METHODS: Culture and susceptibility results were collected prospectively for a 3-month period (April through June 1999) in each of the surgical, trauma, and medical ICUs. The number of unique isolates and susceptibility patterns were determined. Susceptibility of isolates among ICUs was compared with chi2. RESULTS: Statistically significant differences between ICUs in susceptibility to various antibiotics were found for Staphylococcus aureus, Enterococcus sp, Acinetobacter sp, Enterobacter sp, Klebsiella sp, and Pseudomonas sp. Notably, vancomycin-resistant Enterococcus was not seen in the medical ICU, whereas it was seen in both the surgical and trauma ICUs. Klebsiella spp resistant to ceftazidime were seen only in the trauma ICU. The aminoglycosides and quinolones had attenuated activity against Pseudomonas sp in the surgical ICU, whereas they remained highly effective in the trauma ICU. Cefazolin had no activity against the Enterobacter sp in either of the surgical ICUs, but was highly effective in the medical ICU. CONCLUSION: Although the microbiologic results of this study should not be extrapolated to other institutions, the principle is of value. There is variability between ICUs in a single large teaching hospital in susceptibility of bacterial pathogens to various antibiotics. This may have implications in the design of empiric antibiotic strategies and the planning of the hospital formulary. Hospital wide or composite ICU antibiograms are inadequate for planning empiric therapy in the ICU.

Antibiotic Prophylaxis↗
PubMed2000

Disruption of cyclooxygenase-1 gene results in an impaired response to radiation injury.

Prostaglandins may play an important role in regulating normal renewal of gastrointestinal epithelium, epithelial injury repair, and initiation or progression of intestinal neoplasia. Synthesis of prostaglandins is catalyzed by either of two cyclooxygenase isoforms, Cox-1 and Cox-2. Cox-1 is the predominant cyclooxygenase isoform found in the normal intestine. In contrast, Cox-2 is present at low levels in normal intestine but is elevated at sites of inflammation and in adenomas and carcinomas. To determine directly whether prostaglandins synthesized by Cox-1 or Cox-2 regulate crypt epithelial cell fate after genotoxic or cytotoxic injury, we examined apoptosis, prostaglandin synthesis, and crypt stem cell survival after gamma-irradiation in Cox-1(-/-) and Cox-2(-/-) mice. Cox-1(-/-) mice had increased crypt epithelial cell apoptosis and decreased clonogenic stem cell survival compared with wild-type littermates. PGE(2) synthesis was also diminished in Cox-1(-/-) mice compared with wild-type controls in unstressed intestine and after radiation injury. In contrast, apoptosis, stem cell survival, and intestinal PGE(2) synthesis in Cox-2(-/-) mice after irradiation were the same as in wild-type littermates. Crypt stem cell survival after irradiation was inhibited by a highly specific neutralizing antibody to PGE(2), suggesting that this prostaglandin mediates stem cell fate in vivo. These data suggest that prostaglandins synthesized by Cox-1 regulate multiple steps that determine the fate of crypt epithelial cell after genotoxic or cytotoxic injury.

Animals↗
PubMed1999

FGF-2 enhances intestinal stem cell survival and its expression is induced after radiation injury.

Fibroblast growth factors (FGFs) have mitogenic activity toward a wide variety of cells of mesenchymal, neuronal, and epithelial origin and regulate events in normal embryonic development, angiogenesis, wound repair, and neoplasia. FGF-2 is expressed in many normal adult tissues and can regulate migration and replication of intestinal epithelial cells in culture. However, little is known about the effects of FGF-2 on intestinal epithelial stem cells during either normal epithelial renewal or regeneration of a functional epithelium after injury. In this study, we investigated the expression of FGF-2 in the mouse small intestine after irradiation and determined the effect of exogenous FGF-2 on crypt stem cell survival after radiation injury. Expression of FGF-2 mRNA and protein began to increase at 12 h after gamma-irradiation, and peak levels were observed from 48 to 120 h after irradiation. At all times after irradiation, the higher molecular mass isoform ( approximately 24 kDa) of FGF-2 was the predominant form expressed in the small intestine. Immunohistochemical analysis of FGF-2 expression after radiation injury demonstrated that FGF-2 was predominantly found in the mesenchyme surrounding regenerating crypts. Exogenous recombinant human FGF-2 (rhFGF-2) markedly enhanced crypt stem cell survival when given before irradiation. We conclude that expression of FGF-2 is induced by radiation injury and that rhFGF-2 can enhance crypt stem cell survival after subsequent injury.

Animals↗
PubMed1999

Intestinal mucosal injury in critically ill surgical patients: preliminary observations.

This was a prospective study designed to evaluate the extent to which intestinal mucosal compromise occurs in adult critical care patients with and without systemic inflammatory response syndrome (SIRS) and to correlate the degree of intestinal injury with outcome. Ten patients from a university hospital surgical intensive care unit were identified who manifested SIRS at the time of admission to the intensive care unit. Five other critical care patients without SIRS were also evaluated. The Acute Physiology and Chronic Health Evaluation II score was determined. Intestinal mucosal viability was assessed by serial measurement of serum and urine iFABP intestinal fatty acid binding protein (iFABP), a sensitive and specific marker for mucosal injury. Outcome in terms of the development of multiorgan dysfunction syndrome, adult respiratory distress syndrome, and survival was determined. iFABP was detectable in the serum or urine in 8 out of 10 patients with SIRS. Among the 4 patients with detectable serum iFABP, 2 died and 1 developed severe adult respiratory distress syndrome. Nine of 11 patients without detectable serum iFABP recovered without major morbidity. iFABP was detectable in most patients with SIRS, suggesting that subclinical intestinal mucosal compromise is a frequent component of this syndrome. When iFABP was detectable, particularly in the serum, the prognosis was poor, even in the absence of SIRS, indicating that iFABP may be a relevant and independent predictor of outcome in critical care patients.

Adolescent↗
PubMed1998

Angiography for preoperative evaluation in patients with lower gastrointestinal bleeding: are the benefits worth the risks?

OBJECTIVE: To evaluate the benefits and risks of selective angiography for the evaluation of acute lower gastrointestinal (GI) bleeding to identify the site of bleeding and theoretically limit the extent of colonic resection. DESIGN: Retrospective chart review. SETTING: Tertiary care hospital. PATIENTS: Sixty-five patients undergoing 75 selective angiograms for evaluation of acute lower GI bleeding. Mean age was 71 years (range, 27-93 years), and 37 (57%) were women. MAIN OUTCOME MEASURES: Demographic data were collected that included any associated medical problems, potential factors contributing to an increased risk for bleeding, and the diagnostic methods used in evaluating the source of lower GI bleeding. The details of angiography procedures were recorded with special attention to the impact of the procedure on clinical management and any associated complications. RESULTS: Twenty-three patients (35%) had positive angiography findings, and 14 of them (61%) required operations. Forty-two patients (65%) had negative angiography findings, and 8 of them (19%) required operations. Surgery for the 22 patients included hemicolectomy in 11 patients, subtotal colectomy in 10 patients, and small-bowel tumor resection in 1 patient. In 9 patients, a hemicolectomy was performed on the basis of angiography findings. Three patients (2 with negative angiography findings) experienced rebleeding after a hemicolectomy and required a subsequent subtotal colectomy. Overall, only 8 (12%) of the 65 patients underwent a segmental colon resection that was based on angiography findings and did not bleed after their operation. Complications from angiography occurred in 7 patients (11%). CONCLUSION: Selective angiography appears to add little clinically useful information in patients with acute lower GI bleeding and carries a relatively high complication risk.

Adult↗
PubMed1998

Fiberoptic endoscopic documentation of the high incidence of aspiration following extubation in critically ill trauma patients.

The purpose of this study was to investigate the incidence of aspiration following extubation in critically ill trauma patients. This prospective pilot study included 20 consecutive trauma patients who required orotracheal intubation for at least 48 hours. All subjects underwent a bedside transnasal fiberoptic endoscopic evaluation of swallowing at 24 +/- 2 hr after extubation to determine objectively aspiration status. Aspiration was defined as the entry of a blue dyed material into the airway below the level of the true vocal folds, with silent aspiration occurring in the absence of any external behavioral signs such as coughing or choking. Aspiration was identified in 9 of 20 (45%) subjects and 4 of these 9 (44%) were silent aspirators. Therefore, silent aspiration occurred in 20% of the study population. Eight of the 9 (89%) aspirating subjects resumed an oral diet from 2-10 days (mean, 5 days) following extubation. All subjects had no evidence of pulmonary complications. It was concluded that trauma patients after orotracheal intubation and prolonged mechanical ventilation have an increased risk of aspiration. An objective assessment of dysphagia to identify aspiration may reduce the likelihood of pulmonary complications after extubation.

Adolescent↗
PubMed1998

Prostaglandins prevent decreased epithelial cell proliferation associated with dextran sodium sulfate injury in mice.

BACKGROUND & AIMS: Although dextran sodium sulfate (DSS)-induced colitis is a commonly used model of colonic injury, the mechanism of this model is not understood. The aim of this study was to determine the contribution of prostaglandins to the mechanism of DSS-induced epithelial injury. METHODS: Mice were treated with 3% DSS in the drinking water for 5 days followed by water only (recovery). Tissue prostaglandin E2 (PGE2) levels were measured, proliferating cells per cecal crypt were determined by bromodeoxyuridine labeling, and the cellular localization of cyclooxygenase (COX)-1 and COX-2 was determined by immunohistochemistry. RESULTS: DSS decreased the number of proliferating epithelial cells per crypt by approximately 90% and decreased the height of cecal crypts by 40%. Administration of dimethyl PGE2 with DSS reversed the effect of DSS on proliferation but not its effect on crypt shortening. COX-1 was expressed in the crypt epithelium and lamina propria mononuclear cells; DSS treatment down-regulated COX-1 expression only in the epithelium. Dimethyl PGE2 reversed the effect of DSS on COX-1 expression. Recovery was associated with a return to normal COX-1 expression in the epithelium. COX-2 was expressed in lamina propria mononuclear cells. CONCLUSIONS: Epithelial cell proliferation in the presence of DSS contains a PGE2-sensitive component.

16,16-Dimethylprostaglandin E2↗
PubMed1998

Fibrin glue terminates massive bleeding after complex hepatic injury.

OBJECTIVE: We determined the ability of a packaged fibrin glue (FG) product to terminate severe bleeding in a new porcine model of complex hepatic injury. METHODS: Femoral arterial and venous catheters were placed in pentobarbital-anesthetized swine (n=7 per group, 16-18 kg). Pigs received an external blast to the right upper abdomen at 0 minutes, followed by uncontrolled hemorrhage at 0 to 30 minutes, with anticoagulation (heparin, 200 U/kg) at 10 minutes. Pigs were resuscitated with lactated Ringer's solution (20 mL/kg) beginning at 15 minutes and then underwent laparotomy to control bleeding at 30 minutes. Lactated Ringer's solution was infused to keep mean arterial pressure greater than 70 mm Hg until 120 minutes, when repeat laparotomy was performed. Control animals (group 1) underwent routine surgical procedures to terminate bleeding followed by packing if hepatic bleeding continued. The FG animals (group II) underwent routine surgical procedures plus application of FG. Avoidance of packing, estimated blood loss (EBL) during and after laparotomy, and fluid resuscitation volume were the primary end points studied. RESULTS: In both groups, mean arterial pressure varied significantly from baseline to 120 minutes (group I: 100+/-3 to 52+/-11 mm Hg; group II: 99+/-4 to 66+/-3 mm Hg). Temperature decreased at the end of each experiment (group I: 37+/-1 to 33+/-1 degrees C; group II: 37+/-1 to 34+/-1 degrees C). There were no group differences in EBL before laparotomy (0-30 minutes), but from initial laparotomy to repeat laparotomy (30-120 min), EBL (group I: 875+/-265 mL; group II: 300+/-59 mL) and total fluid resuscitation (group I: 2.9+/-0.4 L; group II: 1.9+/-0.3 L) were statistically significantly less in FG pigs. Of greatest importance, six of seven control pigs required packing, but none of the FG animals were packed and none bled at repeat laparotomy. CONCLUSION: FG stopped bleeding and eliminated the need for packing in a model of severe liver injury. Further work in the clinical arena is warranted to determine the potential benefits of FG in arresting hemorrhage in hypotensive, hypothermic, coagulopathic trauma patients with complex visceral injuries.

Animals↗
PubMed1998

Minimal head trauma in children revisited: is routine hospitalization required?

OBJECTIVE: Children with a question of occult head injury are routinely hospitalized despite having both normal central nervous system (CNS) and computed tomographic (CT) scan examinations. We determined the incidence of significant CNS morbidity after occult head injury to determine whether or not hospital admission was necessary in children after minimal head trauma. METHODS: We reviewed the records of children admitted to a level I trauma center with a question of closed head injury, an initial Glasgow Coma Scale equal to 15, a normal neurologic exam, and a normal head CT scan. Children with associated injuries requiring admission were excluded. The endpoints were deterioration in CNS exam, new CT findings, and the need for a prolonged hospital stay. RESULTS: Sixty-two patients were studied with a mean age of 7 years (range, 1 month to 15 years), and 65% were male. The primary mechanisms of injury were fall (45%) and vehicular crash (23%). The mean injury severity score was 4 +/- 2. The mean length of stay was 1.2 days (range, 1 to 3 days). Prolonged hospitalization occurred in 9 patients (15%). No child developed significant CNS sequelae warranting hospital admission. Total charges for these hospitalizations were $177 874. CONCLUSIONS: Children undergoing emergency department work-up of occult head injury, who have a normal CNS exam and a normal head CT scan, do not seem to be at risk for significant CNS sequelae. These patients can be discharged home with parental supervision and avoid unnecessary and costly hospitalization.

Adolescent↗
PubMed1997

Crypt stem cell survival in the mouse intestinal epithelium is regulated by prostaglandins synthesized through cyclooxygenase-1.

Prostaglandins (PGs) are important mediators of epithelial integrity and function in the gastrointestinal tract. Relatively little is known, however, about the mechanism by which PGs affect stem cells in the intestine during normal epithelial turnover, or during wound repair. PGs are synthesized from arachidonate by either of two cyclooxygenases, cyclooxygenase-1 (Cox-1) or cyclooxygenase-2 (Cox-2), which are present in a wide variety of mamalian cells. Cox-1 is thought to be a constitutively expressed enzyme, and the expression of Cox-2 is inducible by cytokines or other stimuli in a variety of cell types. We investigated the role of PGs in mouse intestinal stem cell survival and proliferation following radiation injury. The number of surviving crypt stem cells was determined 3.5 d after irradiation by the microcolony assay. Radiation injury induced a dose-dependent decrease in the number of surviving crypts. Indomethacin, an inhibitor of Cox-1 and Cox-2, further reduced the number of surviving crypts in irradiated mice. The indomethacin dose response for inhibition of PGE2 production and reduction of crypt survival were similar. DimethylPGE2 reversed the indomethacin-induced decrease in crypt survival. Selective Cox-2 inhibitors had no effect on crypt survival. PGE2, Cox-1 mRNA, and Cox-1 protein levels all increase in the 3 d after irradiation. Immunohistochemistry for Cox-1 demonstrated localization in epithelial cells of the crypt in the unirradiated mouse, and in the regenerating crypt epithelium in the irradiated mouse. We conclude that radiation injury results in increased Cox-1 levels in crypt stem cells and their progeny, and that PGE2 produced through Cox-1 promotes crypt stem cell survival and proliferation.

Animals↗
PubMed1997

Addressing the myths of cervical spine injury management.

Every year in the United States about 5,000 people sustain a cervical spinal cord injury. Vastly greater numbers present to hospitals after motor vehicle crashes and falls with potential cervical spine injuries (CSI) for evaluation. This group of patients requires very careful management while undergoing evaluation for potential CSI to minimize the potential for spinal cord injury. It is, therefore, incumbent on everyone caring for these patients to distinguish between fact and fiction in regard to CSI management. This article addresses the following areas of controversy: CSI is a rare injury; patients with cranial and facial injuries are at increased risk for CSI; everyone with a significant mechanism of injury needs radiological clearance of their cervical spine; a normal cross-table lateral view radiograph excludes significant CSI; oral intubation of patients with CSI is not safe; a semi-rigid collar prevents movement of the cervical spine; and the evaluation of the cervical spine needs to begin in the resuscitation room in every patient.

Algorithms↗