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Biomedical subjects

J L Rodriguez

Publications and source records attributed to J L Rodriguez.

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

Abdominal vena caval injuries: outcomes remain dismal.

BACKGROUND: The mortality rate for abdominal vena caval injuries remains high. We examined the experience of a level I trauma center to determine factors significant to the outcome in these injuries. METHODS: Forty-seven patients were identified in a retrospective review (1989 to 1999) of patients were identified with abdominal vena caval injury. Data were analyzed by uni- and multivariate methods, including logistic regression. RESULTS: Most of the individuals with abdominal vena caval injuries were young male patients who were injured by penetrating trauma and who were hypotensive on arrival. The severity of injury and the number of organs injured was high. The overall mortality rate was 55%. Nonsurvivors were more often hypotensive in the field with physiologic derangement consistent with hemorrhagic shock. Type and location of injury as well as method of repair were associated with death. Multiple regression analysis revealed that prehospital initial systolic blood pressure and intraoperative bicarbonate levels were independent predictors of survival. CONCLUSIONS: We identified factors related to poor outcome, including suprarenal and retrohepatic location of injury and variables that reflected the evolution of shock. Management should include appropriate resuscitation and ultimately may require novel operative techniques.

Abdominal Injuries↗
PubMed2000

Endotoxin tolerance from lipopolysaccharide pretreatment induces nuclear factor-kappaB alterations not present in C3H/HeJ mice.

BACKGROUND: Lipopolysaccharide (LPS) activation of macrophage (MO) cytokine secretion requires activation and translocation of nuclear factor-kappaB (NF-kappaB). Endotoxin tolerance induced in LPS-responsive C3H/HeN MOs by LPS pretreatment results in decreased tumor necrosis factor (TNF) secretion and altered NF-kappaB activation. C3H/HeJ MOs have a genetic defect that renders them tolerant to LPS activation. We hypothesized that the alterations of NF-kappaB activation seen with LPS tolerance in HeN MOs would be present in HeJ mice. METHODS: MOs from C3H/HeJ and C3H/HeN mice were cultured with +/- 10 ng/mL LPS pretreatment for 24 hours and then stimulated with 1 to 1,000 ng/mL LPS. Activation of NF-kappaB was assayed by gel shift using a 32P-labeled specific oligonucleotide 30 minutes after LPS activation. TNF secretion 6 hours after LPS stimulation was measured by bioassay. RESULTS: LPS stimulation activated NF-kappaB in both HeN and HeJ MOs. We observed decreased NF-kappaB activation and a characteristic mobility shift in endotoxin-tolerant MOs from HeN mice that were not present in HeJ MOs. In contrast with the results in HeN mice, LPS pretreatment did not induce any alterations in NF-kappaB activation in HeJ MOs. LPS-stimulated TNF secretion was decreased in HeN MOs after LPS pretreatment. There was no change in TNF secretion in HeJ MOs, but, overall, TNF secretion by these cells was much less than that seen in HeN cells. CONCLUSION: MOs from C3H/HeN mice rendered LPS-tolerant by low-dose LPS pretreatment have alterations in activation of NF-kappaB not present in LPS-hyporesponsive C3H/HeJ mice.

Animals↗
PubMed2000

Stapled versus hand sewn anastomoses in patients with small bowel injury: a changing perspective.

INTRODUCTION: Recent studies indicate that trauma patients with hollow viscus injuries requiring anastomosis who are managed with stapling have a higher rate of complications than do those in whom a hand-sewn anastomosis is used. We undertook this study to determine whether this finding applied to patients with small bowel trauma at our institution. METHODS: Records of patients with small bowel injuries were retrospectively reviewed. Demographics, severity of injury, injury management, and outcome data were collected. RESULTS: Patients who had their small bowel injuries managed by hand-sewn repair versus resection and stapled anastomosis demonstrated a nonsignificant decrease in overall complication rate (35% vs. 44%) and rate of intra-abdominal complication (10% vs. 18%). Yet the rate of intra-abdominal abscess formation was significantly lower with hand-sewn repair than with resection and stapled anastomosis (4% vs. 13%). However, when hand-sewn primary repairs were excluded from the analysis and injuries that required resection and either stapled or hand-sewn anastomosis were compared, there was a similar overall complication rate (41% vs. 41%) and rate of intra-abdominal complications (17% vs. 21%). CONCLUSION: The rate of intra-abdominal complications did not differ significantly between patients requiring small bowel resection and reanastomosis managed by either a stapled or hand-sewn technique. In our experience, surgical stapling devices appear to be safe for use in repairing traumatic small bowel injury.

Abdominal Injuries↗
PubMed2000

Impaired mitogen-activated protein kinase activation and altered cytokine secretion in endotoxin-tolerant human monocytes.

BACKGROUND: Dysregulation of monocyte/macrophage cytokine production after exposure to multiple inflammatory stimuli may contribute to multiple organ failure and sepsis. Endotoxin (lipopolysaccharide [LPS]) activation of murine macrophage results in the phosphorylation of kinases in the mitogen-activated protein kinase cascade. Pretreatment of murine macrophages with LPS induces LPS-tolerance, with inhibition of LPS-stimulated activation of kinases (ERK1/2 and p38) and diminished release of tumor necrosis factor (TNF). We sought to determine whether similar alterations in LPS-dependent signal transduction are present in LPS-tolerant human peripheral blood monocytes. METHODS: Human peripheral blood monocytes from healthy volunteer donors (n = 12) were incubated in RPMI 1640 culture medium +/- 10 ng/mL of LPS for 18 hours, then stimulated with 0 to 1,000 ng/mL of LPS. Supernatant TNF and interleukin-1 (IL-1) levels were measured after 5 hours by enzyme-linked immunosorbent assay. Activation of the p42/p44 kinases (ERK1/2) was measured 15 minutes after LPS with monoclonal antibodies to diphosphorylated (active) ERK1/2 using novel flow cytometric methods. RESULTS: LPS-tolerant (10 ng/mL LPS pretreatment) human monocytes had significant inhibition of LPS-stimulated TNF secretion but augmented IL-1 release (p < 0.05). Nontolerant human monocytes had a dramatic increase in the percentage of ERK1/2-positive cells in response to an initial stimulation with LPS. This did not occur in the LPS-tolerant cells. Phorbol-12-myristate-13 acetate restored ERK1/2 activation in LPS-tolerant human monocytes. CONCLUSION: LPS-tolerance in human monocytes is associated with inhibition of LPS-stimulated TNF secretion, augmented release of IL-1, and defective activation of mitogen-activated protein kinase cascade (ERK1/2). These results suggest a method of identifying LPS-tolerance and monocyte dysfunction in patients with sepsis.

Cytokines↗
PubMed2000

Defective lipopolysaccharide-dependent ERK 1/2 activation in endotoxin tolerant murine macrophages is reversed by direct protein kinase C stimulation.

Lipopolysaccharide (LPSp) pretreatment inhibits TNF secretion in endotoxin-tolerant macrophages via alterations in signal transduction pathways of LPS activation (LPSa). Protein kinase C inhibitors prevent TNF release in response to LPSa and direct protein kinase C activation with phorbol myristate acetate (PMA) restores TNF secretion after LPSp. In the current experiments the effect of protein kinase C modulation on LPSa-stimulated ERK 1/2 activation was investigated. Murine macrophage TNF production was determined after stimulation with 100 ng/mL of LPSa, +/- 24 h pretreatment with 10 ng/mL of LPSp. Direct protein kinase C activators (PMA or indolactam) or inhibitors (H7 or bisindolylmaleimide) were added 1 h before LPSa. Diphosphorylated ERK 1/2 was assayed after LPSa stimulation by Western blot. LPS tolerance after LPSp was characterized by inhibition of LPSa-stimulated TNF and accompanied by impaired ERK 1/2 activation by LPSa. Protein kinase C activation with PMA or indolactam restored ERK 1/2 activation and TNF secretion. Inhibition of protein kinase C with H7 or bisindolylmaleimide prevented TNF secretion and ERK 1/2 activation by LPSa. These findings suggest that both ERK 1/2 and protein kinase C are required for TNF production in nontolerant macrophages and that LPS tolerance may be associated with an inability to phosphorylate ERK 1/2.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Impaired ex vivo lipopolysaccharide-stimulated whole blood tumor necrosis factor production may identify "septic" intensive care unit patients.

Currently, there is no reliable diagnostic test to identify septic intensive care unit (ICU) patients. We initiated studies to test the hypothesis that in sepsis, the in vivo exposure to endotoxin is detectable by the ex vivo analysis of lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) production. We obtained heparinized whole blood (WB) from 58 ICU patients and 14 healthy controls. The samples were incubated +/-10 ng/mL of LPS at 37 degrees C for 3 h. Plasma TNF levels were measured using enzyme-linked immunoassay (mean +/- standard error of the mean). Clinical data, including ICU length of stay (LOS), ventilator days (VentD), WBC, and positive cultures (Clt+), were obtained retrospectively. A wide range of LPS-stimulated WB TNF production (pg/mL) was observed in ICU patients (4481+/-469) and controls (6706+/-715). Patients were stratified into quartiles (I-IV) on the basis of the distribution of plotted LPS-stimulated TNF values (pg/mL). Patients in quartile I (N = 14) had significantly lower TNF production (< 2000 pg/mL, P < 0.05) and required increased VentD (16 vs. 10 days, P < 0.05) compared to quartiles II-IV (N = 44). Patients in quartile I also had a higher incidence of infection (79 vs. 50%) and longer LOS (18 vs. 13 d) compared to quartiles II-IV. Impaired TNF release may be a manifestation of monocyte endotoxin tolerance and may be useful to diagnose sepsis.

Adult↗
PubMed2000

Simultaneous quantitation of intracellular zidovudine and lamivudine triphosphates in human immunodeficiency virus-infected individuals.

Highly active antiretroviral therapy (HAART) is the standard treatment for infection with human immunodeficiency virus (HIV). The most common HAART regimen consists of the combination of at least one protease inhibitor (PI) with two nucleoside reverse transcriptase inhibitors (NRTIs). Contrary to PIs, NRTIs require intracellular activation from the parent compound of their triphosphate moiety to suppress HIV replication. Simultaneous intracellular determination of two NRTI triphosphates is difficult to accomplish due to their relatively small concentrations in peripheral blood mononuclear cells (PBMCs), requiring large amounts of blood from HIV-positive patients. Recently, we described a method to determine intracellular zidovudine triphosphate (ZDV-TP) concentrations in HIV-infected patients by using solid-phase extraction and tandem mass spectrometry. The limit of quantitation (LOQ) for ZDV-TP was 0.10 pmol, and the method was successfully used for the determination of ZDV-TP in HIV-positive patients. In this study, we enhanced the aforementioned method by the simultaneous quantitation of ZDV-TP and lamivudine triphosphate (3TC-TP) in PBMCs from HIV-infected patients. The LOQ for 3TC-TP was 4.0 pmol, with an interassay coefficient of variation and an accuracy of 7 and 12%, respectively. This method was successfully applied to the simultaneous in vivo determination of the ZDV-TP and 3TC-TP pharmacokinetic profiles from HIV-infected patients receiving HAART.

Anti-HIV Agents↗
PubMed2000

Intracellular studies of the nucleoside reverse transcriptase inhibitor active metabolites: a review.

Nucleoside reverse transcriptase inhibitors (NRTIs) plasma concentrations do not correlate with clinical efficacy or toxicity. These agents need to be phosphorylated to become active against HIV-infection. Thus, the characterization of the NRTIs intracellular metabolite pharmacological parameters will provide a better understanding that could lead to the development of more rational dose regimens in the HIV-infected population. Furthermore, intracellular measurements of NRTIs may provide a better marker with respect to clinical efficacy and toxicity than plasma concentrations. Thus, in this article we review the latest information regarding the intracellular pharmacological parameters of zidovudine (ZDV) and lamivudine (3TC) active metabolites in HIV-infected patients including the results from our recent clinical studies. We will start the discussion with ZDV and 3TC clinical efficacy, followed by systemic pharmacokinetics studies. We will then discuss the in vitro and in vivo intracellular studies with particular emphasis in the method development to measure these metabolites and we will conclude with the most current data from our clinical trials.

Adult↗
PubMed2000

Identification of patients at highest risk for ventilator-associated pneumonia in the surgical intensive care unit.

Ventilator-acquired pneumonia (VAP) is a major problem for patients admitted to the surgical intensive care unit mechanically ventilated. Recently, we have identified both clinical and immunologic factors associated with the development of VAP. The clinical risk factors are associated with the severity of the injury and the length of mechanical ventilation. The immunologic risk factors are associated with the local lung inflammatory response that is unchecked and affects local cell function. The combination of the severity of injury, the length of mechanical ventilation, and the failure to "auto-regulate" the lung response places the host at risk of VAP. In the next millennium, if we are to make significant advances in the management of VAP, we will need to understand the pathophysiology of the disease process. Then we can develop preventive strategies that will reduce the morbidity and the associated cost of VAP.

Age Factors↗
PubMed2000

Trauma in cirrhotics: survival and hospital sequelae in patients requiring abdominal exploration.

Hepatic cirrhosis significantly increases the mortality and morbidity of elective surgery; therefore we hypothesized that cirrhosis would adversely impact outcome after abdominal trauma. We used the trauma registry to identify 17 patients with cirrhosis who sustained trauma injuries requiring emergent exploratory laparotomy. Patients were characterized with respect to age, sex, hospital days, intensive care unit days, and trauma scores. A control group (n = 73) was constructed from the registry by matching age, sex, Injury Severity Score (ISS) and Abbreviated Injury score. Mortality rates were compared by Fisher's exact test and age, ISS, Revised Trauma Score 2, and hospital and intensive care unit days were compared by Student's t test. Despite similar ISS between cirrhotic patients and controls, patients with cirrhosis had a fourfold increase in mortality (mortality odds ratio = 7.2; 95% confidence interval = 2.2-24.0). Cirrhotic trauma patients had a complication rate of 71 per cent and a mortality of 44 per cent. We conclude that cirrhosis is a major independent risk factor for mortality in trauma patients with injuries that require emergent abdominal surgery.

APACHE↗
PubMed1999

Macrophage TNF secretion in endotoxin tolerance: role of SAPK, p38, and MAPK.

PURPOSE: Endotoxin (LPS) activation of macrophages results in phosphorylation of mitogen-activated protein kinases (MAPK), stress-activated protein kinases (SAPK), and p38 kinase. LPS pretreatment inhibits subsequent LPS-stimulated MAPK activation and TNF release and both were reversed if macrophages were treated with phorbol myristate acetate (PMA) before LPS stimulation. In this study we sought to determine if SAPK and p38 tyrosine kinases are required for TNF production and if LPS pretreatment alters their activation. METHODS: TNF production by murine peritoneal exudate macrophages was determined 6 h after stimulation with 100 ng/mL of LPS +/- 24 h pretreatment with 10 ng/mL of LPS. The active, diphosphorylated forms of MAPK (p42, p44), SAPK (p46, p54), and p38 were assayed 30 min after LPS stimulation by Western immunoblot using specific antibodies. In some experiments a p38 kinase inhibitor (SB202190) or the protein kinase C activator (PMA) was added 1 h before LPS stimulation. RESULTS: LPS activated MAPK, SAPK, and p38. LPS pretreatment significantly inhibited MAPK, SAPK, and p38 activation by LPS stimulation. TNF protein secretion and MAPK activation in tolerant macrophages were restored by PMA treatment, but this did not restore SAPK activation. The p38 inhibitor SB202190 blocked LPS-stimulated TNF production. CONCLUSION: LPS pretreatment-induced tolerance decreased LPS-stimulated MAP, SAP, and p38 kinase activation. LPS tolerance in murine macrophages appears to be associated with specific, PMA-reversible defects in MAPK and p38 kinase activation.

Animals↗
PubMed1999

Trauma faculty and trauma team activation: impact on trauma system function and patient outcome.

OBJECTIVE: To determine the impact of the presence of an attending trauma surgeon during trauma team activation on system function and patient outcome. METHODS: After a retrospective review of medical records and trauma registry, a comparative study between two American College of Surgeons Committee on Trauma Level I trauma centers was performed. One center (Hennepin County Medical Center) required a chief surgical resident, two junior residents, and a board-certified emergency medicine faculty to be present in the emergency department for all trauma team activations. The attending trauma surgeon was notified at the time of trauma team activation and was neither required to be present in the emergency department at time of patient arrival nor in the hospital 24 h/day. The other center (St. Paul Ramsey Medical Center) required a chief surgical resident, two junior residents, a board-certified emergency medicine faculty member, and an attending trauma surgeon to be present in the emergency department for all trauma activations and in hospital 24 hours/day. Over a 21-month period, all major trauma patients (Injury Severity Score > 15 or emergent operation within 4 hours of admission and any Injury Severity Score) that triggered trauma team activation were examined. Resuscitation time, time to incision, probability of survival, and mortality were analyzed. RESULTS: Resuscitation time was shorter at St. Paul Ramsey Medical Center when compared with Hennepin County Medical Center. Analysis by mechanism of injury demonstrates that this was true for blunt trauma (39+/-13 vs. 27+/-12 minutes, p = 0.001) and for penetrating trauma (28+/-14 vs. 24+/-17 minutes, p = 0.01). Subgroup analysis of penetrating trauma victims demonstrated that there was a significant difference in resuscitation times for gunshot wounds but not for stabs. There was no difference in how quickly operations could be initiated for blunt trauma patients. However, in penetrating cases, time to incision was significantly shorter at St. Paul Ramsey Medical Center (50+/-29 vs. 66+/-43 minutes, p = 0.01). There was no significant difference in mortality for any category of Trauma and Injury Severity Score probability of survival in blunt or penetrating trauma. Analysis of "in-house" and "out-house" time intervals demonstrated no difference in survival in any mechanism of injury, nor was there a difference in overall mortality. CONCLUSION: The presence of a trauma surgeon on the trauma team reduced resuscitation time and reduced time to incision for emergent operations, particularly in penetrating trauma. However, it had no measurable impact on mortality based on Trauma and Injury Severity Score probability of survival. Attending trauma surgeon presence on the trauma team improves in-hospital trauma system function without affecting patient outcome.

Adult↗
PubMed1999

In vitro macrophage endotoxin tolerance: defective in vitro macrophage map kinase signal transduction after LPS pretreatment is not present in macrophages from C3H/HeJ endotoxin resistant mice.

Altered endotoxin (LPS) signal transduction in macrophages (Mphi) may mediate development of organ dysfunction in sepsis. C3H/HeJ Mphi have a specific genetic defect that renders them "tolerant" to in vitro LPS activation. LPS tolerance can be induced in normal C3H/HeN Mphi following in vitro LPS pretreatment. In these experiments, in vitro LPS-stimulated activation of Mphi mitogen-activated protein (MAP) kinases were compared in C3H/HeJ and C3H/HeN mice. C3H/HeJ and C3H/HeN Mphi were cultured+/-10 ng/mL LPS pretreatment for 24 h, then stimulated with 0-1,000 ng/mL LPS for 6 h. Western blots were performed on lysates with monoclonal antibody to active ERK1,2 (p42/44), stress-activated protein kinase (SAPK, p54/46), and p38 kinase. Supernatant TNF or IL-1 was determined by bioassay. High dose LPS stimulation activated ERK, SAPK, and p38 kinases in both C3H/HeN and C3H/HeJ Mphi. ERK activation, p46 SAPK, and p38 activation were inhibited in C3H/HeN Mphi after LPS pretreatment, whereas they were unchanged or increased in HeJ Mphi. TNF secretion was significantly decreased in C3H/HeN Mphi following LPS pretreatment, but absent in C3H/HeJ Mphi at all times. Mphi from normal C3H/HeN mice rendered endotoxin tolerant by in vitro, low dose LPS pretreatment have specific signal transduction defects that are not present in genetically LPS hyporesponsive C3H/HeJ mice.

Animals↗
PubMed1999

Inhibitory kappaBalpha control of nuclear factor-kappaB is dysregulated in endotoxin tolerant macrophages.

The transcription factor nuclear factor (NF)-kappaB is thought to be required for endotoxin-stimulated tumor necrosis factor (TNF) and interleukin (IL)-1 gene transcription. Nuclear translocation of NF-kappaB is regulated by the cytoplasmic inhibitory factor IkappaBalpha. Low-dose lipopolysaccharide (LPS) pretreatment modulates cytokine release by altering subsequent LPS-activated signal transduction pathways. In this study, we examined the effect of LPS pretreatment exposure on IkappaBalpha and NF-kappaB following activation with LPS. Murine macrophages (Mphi were exposed to a range of LPS concentrations +/-24 h PreRx with 10 ng/mL LPS pretreatment. Cytoplasmic IkappaBalpha (Western immunoblot) and NF-kappaB (gel-shift assay) were assayed 30 min after LPS activation. Gene transcription for TNF was measured 6 h after LPS activation using RT-PCR. In the absence of LPS pretreatment, IkappaBalpha disappeared from the cytoplasm coincident with nuclear translocation of NF-kappaB. Tolerant Mphi had markedly enhanced levels of IkappaBalpha and normal to increased levels of NF-kappaB translocation with a different electrophoretic shift. LPS activation enhanced cytokine gene transcription in a dose-dependent manner, and this was unaltered by LPS pretreatment. Endotoxin-tolerant Mphi also had increased cytoplasmic levels of the p65 subunit of NF-kappaB. LPS tolerance is associated with increases of cytoplasmic IkappaBalpha p65, as well as enhanced NF-kappaB. We conclude that control of NF-kappaB translocation by IkappaBalpha is dysregulated in endotoxin-tolerant Mphi.

Animals↗
PubMed1999

Wound management in perforated appendicitis.

Open wound management after perforated appendicitis was common practice but, recently, primary closure has been advocated to reduce costs and morbidity. Hospital records from 319 adults who underwent appendectomy from 1993 to 1996 were reviewed to identify surgical wound infections (SWIs) and examine risk factors. Information about age, length of stay (LOS), operative time, white blood cell count, and antibiotic administration were obtained. Perforation was either noted at operation or identified microscopically by the pathologist. If primary wound closure was performed, patients with acute appendicitis and perforation had a 4-fold higher readmission rate, a 5-fold increase in SWI, and twice the LOS compared with patients with acute appendicitis without perforation. Patients with grossly perforated acute appendicitis had no difference in LOS if the wound was treated open or closed primarily. No patient with microscopic perforation and primary wound closure developed SWI. Primary wound closure after acute appendicitis was safe in the absence of clinical perforation. In the presence of clinical appendiceal perforation the wound should be left open.

Acute Disease↗
PubMed1999

Initial experience with laparoscopic live donor nephrectomy.

BACKGROUND: Advances in laparoscopic instruments and video technology have made laparoscopic donor nephrectomy (LDN) feasible. We report our initial experience with this technique. METHODS: A retrospective review of 30 open donor nephrectomies and our first 30 LDNs was performed to assess donor and recipient outcome and resource usage. RESULTS: LDN was successfully completed in 26 donors (87%). The increased operative time and costs were balanced by less postoperative pain, earlier discharge, earlier return to normal activity and work, fewer incision problems, and less personal financial loss. Recipient outcome was not affected. CONCLUSION: LDN is technically feasible and safe, and recipient graft outcomes are equivalent. Convalescence is shortened, and there is less personal financial loss. LDN offers significant benefit to the donor and may result in increased organ donation.

Adult↗
PubMed1999

Civilian rectal trauma: a changing perspective.

BACKGROUND: Recently the Organ Injury Scaling Committee of the American Association for the Surgery of Trauma developed a Rectal Injury Scaling System (RISS). Little data exist regarding its clinical utility. METHODS: We retrospectively reviewed 45 patients with rectal injuries to assess the impact of the RISS on patient management and outcome. We compared RISS grade I patients (group I, partial-thickness injury) with patients with grades 2, 3, and 4 injuries (group II, full-thickness injury). RESULTS: Group II underwent distal rectal washout and repair of the injury twice as often and had a significantly higher rate of diversion of the fecal stream. This was associated with a 3-fold increase in complications. The only complications in group I were in patients managed with diversion of the fecal stream and distal rectal washout. CONCLUSIONS: Our data suggest that aggressive surgical management for RISS grade I injury may not be necessary. Implementation of therapy based on the RISS may improve outcomes of civilian rectal trauma.

Adolescent↗