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L Graff

Publications and source records attributed to L Graff.

At least 19 recordsLinked to original sources
PubMed2001

Expression of vesicular monoamine transporters, synaptosomal-associated protein 25 and syntaxin1: a signature of human small cell lung carcinoma.

Vesicular monoamine transporters (VMATs) are a prerequisite for the uptake of biogenic amines into intracellular storage organelles, whereas soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs; such as SNAP-25 and syntaxin1) are essential for exocytosis of biogenic amines by neurons and endocrine cells. In this study, we examined whether these proteins exist in high-grade malignant small cell lung carcinomas (SCLCs), large cell carcinomas, adenocarcinomas, and squamous cell carcinomas of the lung. We analyzed two established human SCLC cell lines, one adenocarcinoma cell line, paraffin-embedded tumors (SCLC, n = 25; large cell carcinoma, n = 10; adenocarcinoma, n = 10; squamous cell carcinoma, n = 10), and snap-frozen SCLC samples (n = 2). Using immunocytochemistry, Western blotting, Northern blotting, RT-PCR, and sequencing, we identified VMAT1, VMAT2, SNAP-25, and syntaxin1 in cultured SCLC cells. Immunohistochemistry carried out on paraffin sections revealed that all SCLC tumors express VMAT1, VMAT2, SNAP-25, and syntaxin1. The presence of SNAP-25 and syntaxin1 in SCLC was confirmed by RT-PCR performed with material extracted from paraffin sections. Western blot analysis and RT-PCR carried out with snap-frozen SCLC tumors revealed the presence of SNAREs and VMATs. Immunohistochemistry showed that non-SCLC tumors were negative for SNAREs and VMATs, with the exception of immunostaining for SNAP-25 and syntaxin1 in 3 of 10 adenocarcinomas. Our findings indicate that SCLC cells are endowed with transporters necessary for intracellular storage of biogenic amines and with proteins required for exocytosis of secretory products. These proteins may be used as markers of differentiation of human lung tumors. Moreover, the presence of VMATs provides the basis for a diagnostic application of biogenic amine-derived tracers in positron emission tomography of SCLC tumors.

Adenocarcinoma↗
PubMed2000

Implementing emergency department observation units within a multihospital network.

BACKGROUND: The proportion of emergency department (ED) chest pain patients who undergo an extended "rule out MI (myocardial infarction)" evaluation beyond the ED determines both the quality and cost of patient care. The higher an organization's rate of such evaluations, the lower the average miss rate for MI. Five of the 13 hospitals in the Voluntary Hospital Association Northeast multihospital network implemented ED observation units by June 1997 for outpatient rule out MI evaluations. RESULTS: Compared with historical and case controls, the five hospitals with ED observation units had a higher observation rate (16% versus 0% [p < .001] and 2% [p < .001]) and a higher rule out MI evaluation rate (61% versus 46% [p < .01] and 45% [p < .01]), without a significantly higher admission rate (47% versus 46% and 45%). For the three hospitals with observation units that collected charge data during 1997 on a consecutive series of chest pain patients who had negative rule out MI evaluations, charges for patient services were lower for patients evaluated in the ED observation unit ($2,214.80 +/- $80.40) than in the hospital ($5,464.30 +/- $393.60). CONCLUSIONS: ED observation units represent a cost-effective restructuring of the diagnostic approach to patients with acute chest pain. In an improvement of quality of patient care, a larger proportion of ED chest pain patients receive an extended evaluation than is possible with hospital admission as the only ED disposition option.

Chest Pain↗
PubMed2000

Prospective randomized study of analgesic use for ED patients with right lower quadrant abdominal pain.

Giving an analgesic to patients with right lower quadrant (RLQ) pain causes greater alteration of abdominal signs predictive of appendicitis than placebo. A randomized double-blinded controlled trial of 68 patients who received either tramadol or placebo. Absence or presence of seven abdominal signs (tenderness on light and deep palpation, tenderness in the RLQ and elsewhere, rebound, cough, and percussion tenderness) and pain (100 mm Visual Analog Scale [VAS]) at 0 and 30 minutes were recorded. The predictive value of each physical finding (PF) was measured using an 11-point PF score weighted by likelihood ratios. There was significant reduction in mean VAS of 14.2 mm (95% CI 5.6 to 22.8) in analgesic group versus 6.5 mm (95% CI 1.6 to 11.4) in placebo group. The analgesic group had less normalization of signs as measured by the PF score in all patients [32 of 154 (20.8%) versus 40 of 121 (33.1 %) (P = .031)] and in those with proven appendicitis [4 of 33 (12.1%) versus 10/22 (45.5%) (P = .014)]. Parenteral use of tramadol in emergency department patients with RLQ pain resulted in significant levels of pain reduction without concurrent normalisation of abdominal examination findings indicative of acute appendicitis.

Abdominal Pain↗
PubMed2000

Triage of patients for a rapid (5-minute) electrocardiogram: A rule based on presenting chief complaints.

STUDY OBJECTIVE: A rule based on presenting chief complaints can identify patients for a rapid (5-minute) ECG and decrease delays in treatment of patients with acute myocardial infarction (MI). METHODS: The presenting chief complaint was electronically collected on all patients treated in a community teaching hospital emergency department. A rule for ordering ECG on patient presentation to the ED was developed from a model set of patients presenting from July through December 1994 (22,717 patients) and then tested on a validation set of patients from January through May 1995 (18,759 patients). Outcome measures (delay in performance of ECG and delay in administration of thrombolytic agents) were prospectively collected on written data sheets before (April 1993-May 1995, n=67) and after (June 1995-March 1997, n=128) implementation of the rule at the study hospital. RESULTS: On the model set, 193 patients had the final diagnosis of MI, with 5 chief complaints having the best performance in identifying patients with acute MI and comprising the rapid ECG rule: older than 30 years with chest pain (130 [67.4%] patients); older than 50 years with syncope (5 [1%] patients); weakness (12 [6.2%] patients); rapid heart beat (2 [1%] patients); and difficulty breathing or shortness of breath (20 [10.4%] patients). On the validation set, 142 patients had the final diagnosis of MI, with the rule performing better than chest pain in identifying patients for a "stat" ECG (sensitivity 93.7% versus 67. 4% [95% confidence interval (CI) of the difference, 15.6% to 33.8%]), although a larger percentage of ED patients would receive a stat ECG (7.3% versus 6.3% [95% CI of the difference, 0.7% to 1.7%]). During the model and validation period, 44 (13.1%) of 335 patients with MI received thrombolytic agents. The rule had higher sensitivity on patients with MI treated with thrombolytic agents compared with patients with MI not treated with thrombolytic agents (sensitivity 100% versus 86.4% [95% CI of the difference, 1.7% to 20. 3%] and specificity of 90.4% versus 93.8% [95% CI of the difference, 3.0% to 3.8%]). For the 4-year study period, outcome improved after the implementation of the rule: mean delay in performing ECGs in patients with MI who were administered thrombolytic agents decreased from 10.0 to 6.3 minutes (95% CI of the difference, 1.1 to 6.4), and mean delay in administering thrombolytic agents decreased from 36.9 to 26.1 minutes (95% CI of the difference, 3.5 to 17.7). CONCLUSION: Use of a rule based on chief complaints can identify patients with MI for immediate ECG and decrease delays in performing ECGs and administration of thrombolytic agents.

Adult↗
PubMed2000

False-negative and false-positive errors in abdominal pain evaluation: failure to diagnose acute appendicitis and unnecessary surgery.

OBJECTIVES: To test the hypothesis that physician errors (failure to diagnose appendicitis at initial evaluation) correlate with adverse outcome. The authors also postulated that physician errors would correlate with delays in surgery, delays in surgery would correlate with adverse outcomes, and physician errors would occur on patients with atypical presentations. METHODS: This was a retrospective two-arm observational cohort study at 12 acute care hospitals: 1) consecutive patients who had an appendectomy for appendicitis and 2) consecutive emergency department abdominal pain patients. Outcome measures were adverse events (perforation, abscess) and physician diagnostic performance (false-positive decisions, false-negative decisions). RESULTS: The appendectomy arm of the study included 1, 026 patients with 110 (10.5%) false-positive decisions (range by hospital 4.7% to 19.5%). Of the 916 patients with appendicitis, 170 (18.6%) false-negative decisions were made (range by hospital 10.6% to 27.8%). Patients who had false-negative decisions had increased risks of perforation (r = 0.59, p = 0.058) and of abscess formation (r = 0.81, p = 0.002). For admitted patients, when the inhospital delay before surgery was >20 hours, the risk of perforation was increased [2.9 odds ratio (OR) 95% CI = 1.8 to 4.8]. The amount of delay from initial physician evaluation until surgery varied with physician diagnostic performance: 7.0 hours (95% CI = 6.7 to 7.4) if the initial physician made the diagnosis, 72.4 hours (95% CI = 51.2 to 93.7) if the initial office physician missed the diagnosis, and 63.1 hours (95% CI = 47.9 to 78.4) if the initial emergency physician missed the diagnosis. Patients whose diagnosis was initially missed by the physician had fewer signs and symptoms of appendicitis than patients whose diagnosis was made initially [appendicitis score 2.0 (95% CI = 1.6 to 2.3) vs 6.5 (95% CI = 6.4 to 6.7)]. Older patients (>41 years old) had more false-negative decisions and a higher risk of perforation or abscess (3.5 OR 95% CI = 2.4 to 5.1). False-positive decisions were made for patients who had signs and symptoms similar to those of appendicitis patients [appendicitis score 5.7 (95% CI = 5.2 to 6.1) vs 6.5 (95% CI = 6.4 to 6.7)]. Female patients had an increased risk of false-positive surgery (2.3 OR 95% CI = 1.5 to 3.4). The abdominal pain arm of the study included 1,118 consecutive patients submitted by eight hospitals, with 44 patients having appendicitis. Hospitals with observation units compared with hospitals without observation units had a higher "rule out appendicitis" evaluation rate [33.7% (95% CI = 27 to 38) vs 24.7% (95% CI = 23 to 27)] and a similar hospital admission rate (27.6% vs 24.7%, p = NS). There was a lower miss-diagnosis rate (15.1% vs 19.4%, p = NS power 0.02), lower perforation rate (19.0% vs 20.6%, p = NS power 0.05), and lower abscess rate (5.6% vs 6.9%, p = NS power 0.06), but these did not reach statistical significance. CONCLUSIONS: Errors in physician diagnostic decisions correlated with patient clinical findings, i.e., the missed diagnoses were on appendicitis patients with few clinical findings and unnecessary surgeries were on non-appendicitis patients with clinical findings similar to those of patients with appendicitis. Adverse events (perforation, abscess formation) correlated with physician false-negative decisions.

Abdominal Pain↗
PubMed1999

Reflex testing II: evaluation of an algorithm for use of cardiac markers in the assessment of emergency department patients with chest pain.

A reflex algorithm was developed and evaluated for the use of serum cardiac markers for the diagnosis and rule out of acute myocardial infarction (AMI), and risk stratification of unstable angina patients for those who present to emergency departments (ED) with chest pain. The process begins with testing of total CK and myoglobin at admission. Based on these results, the algorithm determines the need for subsequent testing for the CK-MB isoenzyme and cardiac troponin I (cTnI). The algorithm also directs the need for further blood collection and cardiac marker testing at 4, 8, and 12 h after presentation. A total of eleven stopping points were identified. For some of these stopping points, the algorithm concluded that further blood collections and testing was unnecessary and redundant. The algorithm was retrospectively evaluated on 101 non-consecutive chest pain patients who presented to the EDs at three hospitals. For the AMI group (n=34), six of nine possible different stopping points were reached: 64.7% of cases were diagnosed with the first sample at admission, an additional 32.3% after 4 h, and 2.9% at 8 h. The 12-h sample was not necessary for any of the AMI patients. For the non-AMI group (n=67), most reached the stopping point of no cardiac injury or risk. There were five unstable angina patients who had minor myocardial damage on the basis of a marginally increased cTnI. Of these, one patient subsequently suffered AMI, and three others required angioplasty or bypass surgery. Compared to performing four tests on all patient samples, the reflex algorithm would have reduced the number of necessary tests from 442 to 130 (71% reduction) for AMI patients, and 871 to 469 (46% reduction) for non-AMI patients, if prospectively implemented.

Algorithms↗
PubMed1999

Correlation of the Agency for Health Care Policy and Research congestive heart failure admission guideline with mortality: peer review organization voluntary hospital association initiative to decrease events (PROVIDE) for congestive heart failure.

STUDY OBJECTIVE: We quantify patient risk as related to the presence or absence of the Agency for Health Care Policy and Research (AHCPR) congestive heart failure (CHF) hospital admission criteria. METHODS: This was a retrospective observational cohort study at 12 acute care hospitals examining consecutive patients with the final primary diagnosis of CHF. Trained record abstractors blinded to outcome extracted 386 data elements, including 6 AHCPR admission criteria: (1) pulmonary edema (determined by radiograph) or severe respiratory distress (respiration >40 breaths/min), (2) hypoxia (oxygen saturation <90%) not caused by pulmonary disease, (3) significant edema (>/=+2) or anasarca, (4) symptomatic hypotension (<90 mm Hg systolic blood pressure) or syncope, (5) CHF of recent onset, and (6) clinical evidence (chest pain) of myocardial ischemia. The association between admission criteria and mortality rate (30 days, 6 months, and 1 year) was quantified and risk adjusted by stepwise logistic regression analysis. RESULTS: Of the 1,674 patients with CHF, 1,340 (80%) were admitted to the hospital. Patients not admitted had a lower mortality rate than admitted patients (30-day mortality rate, 2.1% [95% confidence interval [CI] 0.6 to 3.6] versus 11.5% [95% CI 9.8 to 13.2]; odds ratio 0.20 [95% CI 0.09 to 0.45]). Two of the admission criteria did not correlate with a higher mortality rate: CHF of recent onset and myocardial ischemia. Excluding those 2 criteria, the number of admission criteria present correlated with the patient's probability of hospital admission (P <.001), length of hospital stay (P =.014), and 30-day mortality rate (P <.0001). When zero or 1 admission criteria was present, physician clinical judgment did distinguish patients less likely to die in the subsequent 30 days (1.5% [95% CI 0.2 to 2.8] sent home versus 10.2% [95% CI 8.5 to 11.9] admitted). When 2 or more admission criteria were present, physician clinical judgment did not distinguish patients less likely to die in the subsequent 30 days (18.2% [95% CI 0 to 42.0] sent home versus 19.4% [95% CI 13.6 to 25.2] admitted). CONCLUSION: Selected criteria of the AHCPR CHF admission guideline correlate with mortality rate. Combined with physician clinical judgment, they may be useful in the risk stratification of patients with CHF. Selected low-risk patients with CHF identified by the admission criteria who are presently managed in the acute care hospital may be candidates for outpatient management. [Graff L, Orledge J, Radford MJ, Wang Y, Petrillo M, Maag R: Correlation of the Agency for Health Care Policy and Research congestive heart failure admission guideline with mortality: Peer Review Organization Voluntary Hospital Association Initiative to Decrease Events (PROVIDE) for congestive heart failure.

Aged↗
PubMed1999

Interobserver variability among faculty in evaluations of residents' clinical skills.

OBJECTIVE: To describe interobserver variability among emergency medicine (EM) faculty when using global assessment (GA) rating scales and performance-based criterion (PBC) checklists to evaluate EM residents' clinical skills during standardized patient (SP) encounters. METHODS: Six EM residents were videotaped during encounters with SPs and subsequently evaluated by 38 EM faculty at four EM residency sites. There were two encounters in which a single SP presented with headache, two in which a second SP presented with chest pain, and two in which a third SP presented with abdominal pain, resulting in two parallel sets of three. Faculty used GA rating scales to evaluate history taking, physical examination, and interpersonal skills for the initial set of three cases. Each encounter in the second set was evaluated with complaint-specific PBC checklists developed by SAEM's National Consensus Group on Clinical Skills Task Force. RESULTS: Standard deviations, computed for each score distribution, were generally similar across evaluation methods. None of the distributions deviated significantly from that of a Gaussian distribution, as indicated by the Kolmogorov-Smirnov goodness-of-fit test. On PBC checklists, 80% agreement among faculty observers was found for 74% of chest pain, 45% of headache, and 30% of abdominal pain items. CONCLUSIONS: When EM faculty evaluate clinical performance of EM residents during videotaped SP encounters, interobserver variabilities are similar, whether a PBC checklist or a GA rating scale is used.

Clinical Competence↗
PubMed1999

Academic emergency medicine's future. The SAEM Task Force on Emergency Medicine's Future. Society for Academic Emergency Medicine.

Emergency medicine (EM) will change over the next 20 years more than any other specialty. Its proximity to and interrelationships with the community, nearly all other clinicians (physicians and nonphysicians), and scientific/technologic developments guarantee this. While emergency physicians (EPs) will continue to treat both emergent and nonemergent patients, over the next decades our interventions, methods, and place in the medical care system will probably become unrecognizable from the EM we now practice and deliver. This paper, developed by the Society for Academic Emergency Medicine (SAEM) Task Force on Academic Emergency Medicine's Future, was designed to promote discussions about and actions to optimize our specialty's future. After briefly discussing the importance of futures planning, it suggests "best-case," "worst-case," and most probable future courses for academic EM over the next decades. The authors predict that EPs will practice a much more technologic and accurate form of medicine, with diagnostic, patient, reference, and consultant information rapidly available to them. They will be at the center of an extensive consultation network stemming from major medical centers and the purveyors of a sophisticated home health system, very similar to or even more advanced than what is now delivered on hospital wards. The key to planning for our specialty is for EM organizations, academic centers, and individuals to act now to optimize our possible future.

Academic Medical Centers↗
PubMed1997

Improving chest pain evaluation within a multihospital network by the use of emergency department observation units.

BACKGROUND: Since 1993 the 13 VHA Southern New England (VHA-SNE) hospitals have been engaged in a regionally sponsored initiative to analyze and improve selected clinical processes. Nine of these hospitals have chosen to participate in an initiative in which observation units were postulated to offer a tool for improving the care of patients with chest pain-the VHA initiative to Implement Chest Pain Treatment in Observation Units. THE FIVE PHASES: In phase 1 of the initiative, the VHA-SNE's Clinical Benchmarking Work Group reviewed the medical literature, which confirmed longstanding systemic and pervasive problems in the evaluation of chest pain patients. The work group's preferred practice was the outpatient "rule out myocardial infarction [MI] evaluation" program during monitored observation; serial testing can accurately diagnose low- and moderate-probability patients with MI. In Phase 2 the study group surveyed the emergency departments in the nine hospitals, discovering significant variation in admission rates and practice patterns. During phase 3 the work group identified a health care organization demonstrating best-practice performance--one of the few hospitals in the nation with an operational outpatient "rule out MI evaluation" program. A team site-visited that organization and recorded information about its structure and processes. VHA-SNE then published a monograph that identified its current performance, described the best-practice approach, offered strategies to implement the model program, and analyzed the financial implications and return on investment. In phase 4 a pilot hospital implemented the model program, which in phase 5 is being extended to the other hospitals represented in the work group. Information regarding protocols, lessons learned, and barriers to implementation was freely provided.

Chest Pain↗
PubMed1995

In vitro and in vivo comparative studies on chelation of aluminum by some polyaminocarboxylic acids.

Since desferrioxamine exhibits toxic effects, the possible use of several other therapeutic agents in acute aluminum intoxication has been investigated in this study. The potential for the chelation of aluminum (Al) by different compounds has been first determined using two in vitro techniques. The formation of stable complexes with Al in an aqueous solution has been evaluated by using pulse polarography. This technique allows the influence of temperature and of calcium (Ca) to be studied for each compound. Certain compounds (HEDTA, DTPA) showed extensive chelation in the presence of Ca2+ at a temperature of 37 +/- 1 degree C. An ultrafiltration technique combined with Al determination by atomic emission spectroscopy (A.E.S.) has allowed the ability of different substances to complex Al that was previously bound to serum proteins, to be estimated. The kinetics of chelation and the minimum efficient concentration have been determined for all of the products studied. The real efficacies of the compounds were studied by in vivo investigations to compare the effectiveness of the best chelating agents (DFO, HEDTA and EDTA) on the distribution and excretion of Al, after repeated i.p. administration to rats. HEDTA shows a chelation potential as widely active as the DFO potential.

Acetates↗