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Biomedical subjects

Reuven Rabinovici

Publications and source records attributed to Reuven Rabinovici.

At least 19 recordsLinked to original sources
PubMed2007

Adenosine deaminase acting on RNA 1 accelerates cell cycle through increased translation and activity of cyclin-dependent kinase 2.

Adenosine-to-inosine RNA editing has been recently implicated in the pathogenesis of inflammation through the upregulation of the editase adenosine deaminase acting on RNA 1 (ADAR1). Because cell proliferation is a key feature of the inflammatory process, the present study tested the hypothesis that overexpression of ADAR1 accelerates cell cycle. To that end, human embryonic kidney 293 cells were transiently transfected with ADAR1 or vector, and cell cycle was evaluated by fluorescence-activated cell sorter. Overexpression of wild-type ADAR1 decreased the proportion of G0-G1 cells (-19%, P<0.01, n=3), increased the percentage of S phase cells (+19%, P<0.01, n=3), and did not change the ratio of cells residing in the G2-M phase (n=3). This finding was supported by three observations. First, there was a parallel production in ADAR1-transfected cells of cyclin-dependent kinase (Cdk) 2 and cyclin A, a pivotal protein complex upregulated at the G1-S phase checkpoint, and of [p]-Histone H1, a marker of Cdk2 activity (+102%, P<0.01, n=3). Second, ADAR1-transfected cells displayed higher activity of the proliferation marker, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide. Third, using anti-ADAR1 antibody, direct binding of ADAR1 to Cdk2 messenger RNA was demonstrated in ADAR1-transfected cells by protein-RNA cross-linking and immunoprecipitation (+974%, P<0.01, n=3). Finally, causal relationships between ADAR1 and Cdk2 were confirmed by a study with the Cdk2 inhibitor, kenpaullone, which prevented the ADAR1-induced shift from the G0-G1 to the S phase. Taken together, these data show that ADAR1 increases cell cycle by shifting cells from the G0-G1 to the S phase through the upregulation of Cdk2.

Adenosine Deaminase↗
PubMed2006

Do not roll the videotape: effects of the health insurance portability and accountability act and the law on trauma videotaping practices.

BACKGROUND: We hypothesized that trauma video practices would be affected as a result of Health Insurance Portability and Accountabilty Act (HIPAA) enactment. METHODS: A survey was distributed electronically to coordinators and/or directors of level 1 trauma centers. Centers were queried on demographics, trauma video use, and reasons for changes, if any, in their video practice patterns. Descriptive statistics and chi-square analysis were employed. RESULTS: Survey response rate was 75%. Prior to HIPAA, 58% of responding trauma centers used video compared to 18% now. On a Likert scale of 1-5, video analysis rated 3.80. For those using video currently, the most common purposes are education (91%) and quality assurance (83%). HIPAA has affected the way video is used at one third of these centers. Ten percent receive institutional review board approval for videotaping, 35% get patient consent, and more than half report capturing a poor patient outcome on tape. The most commonly cited reasons for stopping video use were HIPAA and legal concerns about patient privacy, consent, and discoverability (79%). Scarce resources were, in part, to blame at 70% of centers, while video technology was found to be ineffective at only 32%. CONCLUSIONS: A minority of level I trauma centers currently use video, although it is effective according to users. HIPAA and medicolegal concerns have affected its use at some centers and contributed to its abandonment at others.

Data Collection↗
PubMed2006

Is it safe to delay appendectomy in adults with acute appendicitis?

OBJECTIVE: To examine whether delayed surgical intervention in adult patients with acute appendicitis is safe by correlating the interval from onset of symptoms to operation (total interval) with the degree of pathology and incidence of postoperative complications. SUMMARY BACKGROUND DATA: Prompt appendectomy has long been the standard of care for acute appendicitis because of the risk of progression to advanced pathology. This time-honored practice has been recently challenged by studies in pediatric patients, which suggested that acute appendicitis can be managed in an elective manner once antibiotic therapy is initiated. No such data are available in adult patients with acute appendicitis. METHODS: A retrospective review of 1081 patients who underwent an appendectomy for acute appendicitis between 1998 and 2004 was conducted. The following parameters were monitored and correlated: demographics, time from onset of symptoms to arrival at the emergency room (patient interval) and from arrival to the emergency room to the operating room (hospital interval), physical, computed tomography (CT scan) and pathologic findings, complications, length of stay, and length of antibiotic treatment. Pathologic state was graded 1 (G1) for acute appendicitis, 2 (G2) for gangrenous acute appendicitis, 3 (G3) for perforation or phlegmon, and 4 (G4) for a periappendicular abscess. RESULTS: The risk of advanced pathology, defined as a higher pathology grade, increased with the total interval. When this interval was <12 hours, the risk of developing G1, G2, G3, and G4, was 94%, 0%, 3%, and 3%, respectively. These values changed to 60%, 7%, 27%, and 6%, respectively, when the total interval was 48 to 71 hours and to 54%, 7%, 26%, and 13% for longer than 71 hours. The odds for progressive pathology was 13 times higher for the total interval >71 hours group compared with total interval<12 hours (95% confidence interval = 4.7-37.1). Although both prolonged patient and hospital intervals were associated with advanced pathology, prehospital delays were more profoundly related to worsening pathology compared with in-hospital delays (P < 0.001). Advanced pathology was associated with tenderness to palpation beyond the right lower quadrant (P < 0.001), guarding (P < 0.001), rebound (P < 0.001), and CT scan findings of peritoneal fluid (P = 0.01), fecalith (P = 0.01), dilation of the appendix (P < 0.001), and perforation (P < 0.001). Increased length of hospital stay (P < 0.001) and antibiotic treatment (P < 0.001) as well as postoperative complications (P < 0.001) also correlated with progressive pathology. CONCLUSION: In adult patients with acute appendicitis, the risk of developing advanced pathology and postoperative complications increases with time; therefore, delayed appendectomy is unsafe. As delays in seeking medical help are difficult to control, prompt appendectomy is mandatory. Because these conclusions are derived from retrospective data, a prospective study is required to confirm their validity.

Acute Disease↗
PubMed2006

The trauma bay chest radiograph in stable blunt-trauma patients: do we really need it?

The current study evaluates the need for trauma bay chest radiographs (CXR) in stable blunt-trauma patients who are scheduled for chest computed tomography (CCT). A retrospective review of 157 randomly selected, stable, adult blunt-trauma patients who were admitted to a level I trauma center between 2000 and 2002, who underwent both CXR and CCT (GE Light-Speed Scanner), was performed. Stable patients were defined as unintubated, normotensive (SBP > 100 mm Hg), and without hypoxia (O2 saturation > 90%). No interventions were conducted in the trauma bay based on chest radiograph findings. Among 95 patients with a "normal" CXR, 38 patients (40%) were found on CCT to have traumatic injuries. Among 62 patients with an "abnormal" CXR, 18 (29%) were found to be normal on CCT. Of the remaining 44 patients, 34 had additional findings on CCT. In 32 patients, CCT led to changes in management. CCT was more sensitive in diagnosing thoracic injuries and led to significant changes in management. We feel that CXR could be safely eliminated in favor of CCT in stable blunt-trauma patients.

Adult↗
PubMed2006

Are resident work-hour limitations beneficial to the trauma profession?

In July 2003, work-hour restrictions were implemented by the Accreditation Council for Graduate Medical Education (ACGME) to limit resident duty hours. Attending surgeon work-hours have not been similarly reduced, and many trauma services have added emergency general surgery responsibilities. We hypothesized that trauma attending/resident work-hour disparity may disincentivize residents from selecting trauma careers and that trauma directors would view ACGME regulations negatively. We conducted a 6-month study of resident and in-house trauma attending self-reported hours at a level I trauma center and sent a questionnaire to 172 national level I trauma directors (TDs) regarding work-hours restrictions. TD survey response rate was 48 per cent; 100 per cent of 15 residents and 6 trauma faculty completed work-hour logs. Attending mean hours (87.1/ wk), monthly calls (5), and shifts > 30 hours exceeded that of all resident groups. Case volume was similar. Residents viewed their lifestyle more favorably than the lifestyle of the trauma attending (Likert score 3.6 +/- 0.5 vs Likert score 2.5 +/- 0.8, P = 0.0003). Seventy-one per cent cited attending work hours and lifestyle as a reason not to pursue a trauma career. Nationally, 80 per cent of trauma surgeons cover emergency general surgery; 40 per cent work greater than 80 hours weekly, compared with < 1 per cent of surgical trainees (P < 0.0001). Most TDs feel that residents do not spend more time reading (89%) or operating (96%); 68 per cent feel patient care has suffered as a result of duty-hours restrictions. Seventy-one per cent feel residents will not select trauma surgery as a career as a result of changes in duty hours. Perceived trauma attending/ resident work-hour disparity may disincentive trainees from trauma career selection. TDs view resident duty-hour restrictions negatively.

Follow-Up Studies↗
PubMed2005

What price for general surgery?

BACKGROUND: This study aims to determine the cost-benefit analysis of adding a full emergency general surgery (EGS) arm to a trauma/critical care (TCC) service with limited EGS activity in a Level I trauma center. METHODS: Data on the composition, activity, and billings of a TCC were collected and compared before (January 1, 2002-June 30, 2003) and after (July 1, 2003-December 31, 2003) it assumed the care of all unassigned EGS patients. These included patient volume and demographics, service, procedures, on-call/service activity, and professional billings and collections. Data are means +/- SD or percentages. Intergroup comparisons were performed by using t test or chi2 as appropriate; significance was assumed for values of p < 0.05. RESULTS: Deploying an EGS arm increased coverage weeks (+52 weeks) and necessitated additional staffing (pre-EGS, n = 5; post-EGS, n = 6). Trauma operative volume remained constant (8.2 vs. 10.3 per month), EGS and elective case load increased (28.7 vs. 60 per month; p < 0.01), and the EGS case/consult ratio decreased from 0.81 to 0.64 (p < 0.01). This expanded activity was associated with reduced on-call nonclinical hours, from 3.2 +/- 0.9 to 1.1 +/- 0.8 (p < 0.01), and increased outpatient visits (68.6 vs. 91.1 per month; p < 0.01) and off-service time used for elective operations (22.3 vs. 76%; p < 0.01). Billings significantly increased in each arm compared with the pre-EGS study period (operating room, +44.8; intensive care unit, +12.5; outpatient, +48.7%; p < 0.01). CONCLUSION: Integrating a full EGS into a TCC service encumbers increased nontrauma unscheduled clinical activity in the operating room, clinic, and floors, which resulted in enhanced billings. These beneficial effects were accrued at the expense of individual time and investment in recruiting additional faculty.

Connecticut↗
PubMed2004

The saliva strip test is an accurate method to determine blood alcohol concentration in trauma patients.

OBJECTIVES: To determine the accuracy of alcohol saliva testing (AST) in trauma patients. METHODS: Blood alcohol concentration (BAC) was measured by using both AST (QED A350; STC Technologies, Bethlehem, PA) and blood serum levels in 100 trauma patients admitted to the emergency department of an urban Level 1 trauma center. RESULTS: All 41 patients who tested positive for BAC on AST (mean [+/-SD]: 167.9 +/- 16.16; range: 20-350 mg/dL) also tested positive on serum determination (mean: 197.6 +/- 13.79; range: 22-446 mg/dL). Correlation between the two positive tests was significant (0.879, p < 0.001). Of the remaining 61 patients, 59 tested negative on both tests, while two patients with BACs of <30 mg/dL tested negative on the AST. For 18 patients with blood in the oropharynx, there was a correlation of 0.976 (p < 0.001, two-tailed) between serum and AST tests. CONCLUSIONS: The AST method of measuring BAC in trauma patients is accurate. Blood in the oral cavity did not appear to affect the accuracy of the test.

Adolescent↗
PubMed2003

Intracellular localization of differentially regulated RNA-specific adenosine deaminase isoforms in inflammation.

Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional process that amplifies the repertoire of protein production. Recently, the induction of this process through up-regulation of the editing enzyme RNA-specific adenosine deaminase 1 (ADAR1) was documented during acute inflammation. Here we report that the inflammation-induced up-regulation of ADAR1 involves differential production and intracellular localization of several isoforms with distinct RNA-binding domains and localization signals. These include the full-length ADAR1 (p150) and two functionally active short isoforms (p80 and p110). ADAR1 p80 starts at a methionine 519 (M519) due to alternative splicing in exon 2, which deletes the putative nuclear localization signal, the Z-DNA binding domain, and the entire RNA binding domain I. ADAR1 p110 is the mouse homologue of the human ADAR1 110-kDa variant (M246), which retains the second half of the Z-DNA binding domain, all RNA binding domains, and the deaminase domain. Additional variations are found in the third RNA binding domain of ADAR1; they are differentially regulated during inflammation, generating isoforms with different levels of activities. Studies in several cell types transfected with ADAR1-EGFP chimeras demonstrated that the p150 and p80 variants are localized in the cytoplasm and nucleolus, respectively. In agreement with this observation, endogenous ADAR1 was identified in the cytoplasm and nucleolus of mouse splenocytes and HeLa cells. Since the ADAR1 variants are differentially regulated during acute inflammation, it suggests that the localization of these variants and of A-to-I RNA editing in the cytoplasm, nucleus, and nucleolus is intracellularly reorganized in response to inflammatory stimulation.

Adenosine↗
PubMed2003

Self-inflicted abdominal stab wounds.

BACKGROUND: Self-inflicted abdominal stab wounds (ASWs) are uncommon. The present study aims to characterize the clinical profile of this unique group of psychiatric-surgical patients. METHODS: A retrospective review of 23 patients with intentional self-inflicted ASWs at two urban level I trauma centres during a 10-year period. RESULTS: Most patients were males (70%), ages ranging from 21 to 82 years (mean 40 years). Seventy-four percent of patients had a previous psychiatric history and prior suicide attempts were common (41%). Half of the patients had a positive admission drug or alcohol screen. Hypotension (systolic blood pressure (SBP) < 90 mmHg) was present in only two patients. Mean injury severity, revised trauma and Glasgow coma scores were 5.8, 7.7 and 14.5, respectively. The most commonly used instrument was a knife (87%). There were 1.5 external wounds per patient located primarily in the right upper quadrant (40%) and right lower quadrant (23%). These were associated with extra-abdominal wounds in 22% of cases. Local wound exploration was positive in 15 patients (65%), who all underwent laparotomy. Injured intra-abdominal or retroperitoneal organs were identified in 10 patients and included the stomach, duodenum, small bowel, colon, mesentery, inferior vena cava (IVC) and psoas muscle with a mean of 1.7 injuries per patient. Wound infection was the only post-operative complication (two patients). All eight patients with a negative local wound exploration were observed without complication. Seventy percent of patients were ultimately transferred to a psychiatric ward with a mean length of stay on the surgical service of 8 days. Only one patient died during admission due to metastatic malignant disease. CONCLUSION: Self-inflicted ASWs in suicidal patients can induce significant although most likely non-lethal abdominal and retroperitoneal injuries. This observation should guide the trauma surgeon when treating such patients.

Abdominal Injuries↗
PubMed2003

Widespread inosine-containing mRNA in lymphocytes regulated by ADAR1 in response to inflammation.

Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional modification of pre-mRNA catalysed by an RNA-specific adenosine deaminase (ADAR). A-to-I RNA editing has been previously reported in the pre-mRNAs of brain glutamate and serotonin receptors and in lung tissue during inflammation. Here we report that systemic inflammation markedly induces inosine-containing mRNA to approximately 5% of adenosine in total mRNA. Induction was the result of up-regulation of A-to-I RNA editing as both dsRNA editing activity and ADAR1 expression were increased in the spleen, thymus and peripheral lymphocytes from endotoxin-treated mice. Up-regulation of ADAR1 was confirmed in vitro in T lymphocytes and macrophages stimulated with a variety of inflammatory mediators including tumour necrosis factor-alpha and interferon-gamma. A late induction of RNA editing was detected in concanavalin A-activated splenocytes stimulated with interleukin-2 in vitro. Taken together, these data suggest that a large number of inosine-containing mRNAs are produced during acute inflammation via up-regulation of ADAR1-mediated RNA editing. These events may affect the inflammatory and immune response through modulation of protein production.

Acute Disease↗