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Biomedical subjects

Michael Heller

Publications and source records attributed to Michael Heller.

16 recordsLinked to original sources

Liquid Biopsy Differentiation of Pancreatic Cancer From Non-Cancerous Pancreatic Disease Using Dielectrophoresis-Recovered Nanoparticles Carrying Cell-Free DNA and Protein Biomarkers.

Cancer-derived extracellular vesicle (EV) nanoparticles carry important biomarkers but are difficult to recover from plasma, making EV-based diagnostics a challenge for clinical settings. Here, we demonstrate nanoparticle-based detection of pancreatic cancer using dielectrophoresis (DEP) nanoparticle recovery technology, which purifies nanoparticles from undiluted plasma and quantifies associated biomarkers. We combined both nanoparticle recovery and biomarker quantification on a single device by simultaneously collecting cell-free DNA nanoparticles and EVs followed by on-chip biomarker fluorescent staining for DNA and Glypican-1. Using a blinded cohort, these biomarkers differentiated pancreatic cancer from benign pancreatic diseases, including cysts, pancreatitis, and precancerous low-grade intraductal papillary mucinous neoplasm (IPMN) lesions, with a sensitivity of 0.92, a specificity of 0.83, and an AUC of 0.93. The AUC increased to 0.97 for patients over 50 years old. This is higher than the standard invasive endoscopic ultrasound-guided fine needle aspiration tissue biopsy procedure (AUC 0.79). This study is among the first demonstrating a combined threshold of DNA and protein levels that can distinguish pancreatic cancer from its precursor IPMN lesions. We also demonstrated the detection of early-stage pancreatic cancer and high-grade in situ precancerous lesions. This DEP-based technique shows that multiple types of cancer-derived nanoparticles can be quickly and easily recovered from plasma making it promising for future clinical diagnostics.

Humans↗

Are all-terrain vehicle injuries becoming more severe?

BACKGROUND: There are several reasons to suspect that injuries from all-terrain vehicles (ATV) have become both more serious and frequent in recent years. These reasons include increasing engine power, younger age of operators and inconsistent enforcement of helmet laws. The purpose of this study was to determine if the increase in ATV injuries was out of proportion to the increase in ATV usage and whether ATV injuries have increased in severity. METHODS: A retrospective analysis of the Consumer Product Safety Commission (CPSC) ATV injury data and the Pennsylvania Trauma System Foundation (PTSF) database from 1989 to 2002 was performed. ATV use, sales, deaths, trauma center admissions, Injury Severity Score (ISS), hospital length of stay (LOS) and Glascow Coma Score (GCS) were reviewed. RESULTS: ATV sales increased to 316%. In the decade prior to 2003, reported deaths nationally increased from 183 to 357 (95%) nationally and from 5 to 10 (100%) in Pennsylvania (PA). Admissions to trauma centers in PA increased 240%, yet the percentage of deaths to trauma center admissions remained constant at 2.6% during this period (p>.50). ISS and LOS from 1989 to 2002 did not significantly change (all p>.05) and GCS improved significantly. CONCLUSION: Despite concerns regarding the increasing dangers associated with ATVs, it appears that the severity of injuries from ATV use has not increased.

Accidents↗

Etomidate versus midazolam for out-of-hospital intubation: a prospective, randomized trial.

STUDY OBJECTIVE: The primary objective of this study is to compare the intubation success rates of etomidate and midazolam when used for sedative-facilitated intubation, without paralytics, in out-of-hospital adult patients. METHODS: This prospective, double-blind, randomized trial was conducted with 2 ground out-of-hospital advanced life support systems (ALS); all patients aged 18 or older who required out-of-hospital sedative-facilitated intubation were eligible for participation. The ambulances were stocked with blinded numbered syringes containing either 7 mg of midazolam or 20 mg of etomidate. No paralytics were used. If sedation was not achieved with the study drug, medics could request additional sedation from a medical command physician; only midazolam or diazepam were available outside of the study. RESULTS: One hundred ten patients were enrolled in the study; 55 patients received midazolam and 55 patients received etomidate. The 2 groups were similar with regard to age, sex, initial vital signs, and reasons for intubation or sedation. The overall intubation success rate was 76% (95% confidence interval [CI] 68% to 84%); 75% (41/55) for midazolam (95% CI 64% to 86%) and 76% (42/55) for etomidate (95% CI 65% to 87%). There was also no difference in incidence of hypotension, number of intubation attempts, or perceived difficulty of intubation. Additional sedation was requested almost equally for the 2 groups: 14 patients in the midazolam group and 12 patients in the etomidate group. A benzodiazepine was successful for rescue of a failed etomidate intubation 10 of 12 times (83%; 95% CI 62% to 100%). When used for rescue of failed midazolam intubations, benzodiazepines were effective in only 5 of 14 (36%, 95% CI 11% to 61%) attempts. CONCLUSION: There were no observed differences between midazolam and etomidate in sedation-facilitated intubation success rates; we could not fully evaluate global outcomes of these agents or the sedative-facilitated intubation strategy itself.

Adolescent↗

Short- and long-term effects of emergency medicine sonography on formal sonography use: a decade of experience.

OBJECTIVES: It has been reported that use of formal sonographic studies by departments of radiology initially increases after inception of an emergency medicine (EM) sonography training program, but there are no data on whether this trend continues as the training program matures. The purpose of this study was to evaluate the effect of an ongoing EM sonography program on formal sonography use after more than a decade of experience. METHODS: This retrospective, computer-assisted review compared emergency department (ED) abdominal sonographic studies ordered in the 3 years before inception of an EM sonography program (1992-1994) with those ordered in the 8 years after its inception (1995-2002). To determine the relative change, all abdominal sonograms ordered by ED physicians were compared with equivalent outpatient formal sonograms by all other physicians in the hospital. The study site is a community teaching hospital with a current ED census of 50,000. RESULTS: In the initial 4 years (1995-1998), the number of formal studies increased significantly in both absolute numbers (annual mean, 95 versus 162; P < .002) and as a percentage of all outpatient sonograms ordered at the institution (5.1% versus 8.5%; P < .0001). However, in the following 4 years (1999-2002), the absolute number of formal studies remained constant but decreased when adjusted for an increased ED census. Emergency department-ordered formal studies also decreased as a percentage of all sonograms ordered (5.1% versus 4.1%; P = .002). CONCLUSIONS: Emergency department use of formal sonography services increases with the introduction of ED sonography but decreases markedly as the program matures.

Abdomen↗

Does the presence or absence of sonographically identified cardiac activity predict resuscitation outcomes of cardiac arrest patients?

This study evaluated the ability of cardiac sonography performed by emergency physicians to predict resuscitation outcomes of cardiac arrest patients. A convenience sample of cardiac arrest patients prospectively underwent bedside cardiac sonography at 4 emergency medicine residency-affiliated EDs as part of the Sonography Outcomes Assessment Program. Cardiac arrest patients in pulseless electrical activity (PEA) and asystole underwent transthoracic cardiac ultrasound B-mode examinations during their resuscitations to assess for the presence or absence of cardiac kinetic activity. Several end points were analyzed as potential predictors of resuscitations: presenting cardiac rhythms, the presence of sonographically detected cardiac activity, prehospital resuscitation time intervals, and ED resuscitation time intervals. Of 70 enrolled subjects, 36 were in asystole and 34 in PEA. Patients presenting without evidence of cardiac kinetic activity did not have return of spontaneous circulation (ROSC) regardless of their cardiac rhythm, asystole, or PEA. Of the 34 subjects presenting with PEA, 11 had sonographic evidence of cardiac kinetic activity, 8 had ROSC with subsequent admission to the hospital, and 1 had survived to hospital discharge with scores of 1 on the Glasgow-Pittsburgh Cerebral Performance scale and 1 in the Overall Performance category. The presence of sonographically identified cardiac kinetic motion was associated with ROSC. Time interval durations of cardiac resuscitative efforts in the prehospital environment and in the ED were not accurate predictors of ROSC for this cohort. Cardiac kinetic activity, or lack thereof, identified by transthoracic B-mode ultrasound may aid physicians' decision making regarding the care of cardiac arrest patients with PEA or asystole.

Adolescent↗

Cardiac cath lab activation by the emergency physician without prior consultation decreases door-to-balloon time.

OBJECTIVE: The purpose of this before-and-after study is to determine whether an ED strategy which calls for cardiac catheterization lab (cath lab) activation directly by the emergency physician (EP) is effective in decreasing door-to-balloon time (DTBT). METHODS: In our active community teaching hospital ED, with an annual census of 55,000, the traditional practice for STEMI required cardiology consultation prior to cath lab notification. In November 2003 we instituted an ED protocol which mandated direct cath lab activation by the EP for eligible STEMI patients without prior notification of the cardiologist. We measured clinically relevant time intervals, including DTBT, prior to and after institution of the protocol. RESULTS: Twenty-four patients were enrolled after institution of the protocol; these were compared to twenty STEMI patients enrolled prior to the new protocol. DTBT decreased significantly, from 118 to 89 minutes, p=.039. Other ED parameters, including door to exam (17 vs. 15 minutes) and total ED time (80 vs. 56 minutes, p = .056) decreased post-protocol but were not significantly different for the two periods. Those arriving by ambulance continued to have a significantly lower DTBT than non-ambulance patients (pre: change of 47 minutes, p = .03, post: change of 33 minutes; p = .012). Both groups were affected similarly by the change in protocol, decreasing DTBT by approximately 25%. CONCLUSION: We conclude that a strategy which mandates cath lab activation by the emergency physician for STEMI without prior cardiology consultation, reduces door to balloon time.

Catheterization↗

EPs do not accept the strategy of "lumbar puncture first" in subarachnoid hemorrhage.

It has been proposed that the workup of suspected subarachnoid hemorrhage should begin with lumbar puncture (LP) rather than computed tomography (CT) scan. We investigated whether EPs would in fact advocate this strategy in an index hypothetical case and in variations of the index case. An eight-question survey was distributed to EM physicians attending national continuing medical education meetings. Questions included whether the responders would advocate "LP first" in the following scenarios: (1) the index case in which the patient's symptoms had been present for more than 12 hours, other diagnoses were very unlikely, the patient was fully insured, and CT scan was available immediately; (2) a case in which the patient is not insured; (3) a case in which the respondent is the patient; and (4) a case in which there is a delay in obtaining a CT scan. Two hundred forty-one of 275 surveys were completed for a response rate of 88%. Given the index scenario, only 22.8% of the respondents would advise patients to have an LP first versus 17.9% if they themselves were the patient (P=.11). Compared with the index scenario, 34.0% of respondents would advise LP first if their patient did not have insurance (P<.0001); a majority, 57.1%, would advise LP first if the CT were delayed (P<.0001). The "LP first" strategy for workup of subarachnoid hemorrhage was rejected by most EM physicians except when the CT scan would entail delay. Compared with the index case, an added number of physicians would advocate this strategy if the patient was uninsured. The ethical implication of advocating a strategy because of financial concerns and that most physicians would not favor for themselves or their patients merits attention.

Emergency Service, Hospital↗

Computed Tomography is Diagnostic in the Cervical Imaging of Helmeted Football Players With Shoulder Pads.

OBJECTIVE: Prospective, observational case series evaluating the value of cervical spine computed tomography (CT) scans in the initial evaluation of a helmeted football player with suspected cervical spine injury. SUBJECTS: Five asymptomatic male football players, fully equipped and immobilized on a backboard. DESIGN: Multiple 3.0-mm, helically acquired, axially displayed CT images of the cervical spine were obtained from the skull base inferiorly through T1, with images filmed at soft tissue and bone windows. Sagittal and coronal reformatted images were performed. Software was used to minimize metallic artifact. MEASUREMENTS: All series were reviewed by a Board-certified neuroradiologist for image clarity and diagnostic capability. RESULTS: Lateral scout films demonstrated mild segmental degradation, depending on the location of the metallic snaps overlying the spine. Anteroposterior scout films and bone window images were of diagnostic quality. The soft tissue windows showed minimal localized artifact occurring at the same levels as in the lateral scout views. This minimal beam-hardening streak artifact did not affect the diagnostic quality of the soft tissue windows. Reconstructed images were uniformly of clinical diagnostic quality. DISCUSSION: When CT scans were reviewed as a unit, sufficient information was available to allow reliable clinical decisions about the helmeted football player. In light of recent publications demonstrating the difficulty of obtaining adequate radiographs to evaluate cervical spine injury in equipped football players, helmeted athletes may undergo CT scanning without any significant diagnostic limitations.

Journal Article↗

Bedside ultrasound to determine prandial status.

The prandial status of ED patients is often unknown. Because a full stomach predisposes patients to aspiration during a variety of urgent interventions, a method of determining the degree of gastric fullness would be of potential clinical importance. The purpose of this single-blind interventional trial was to determine if bedside ultrasound, performed by EPs, could accurately determine prandial status. We enrolled 20 subjects who were randomized to either a fasting or nonfasting group. Three emergency sonographers scanned each subject in both the supine and right lateral decubitus (RLD) positions and independently recorded their determination of the prandial status both before and after ingestion of water. We found that the technique was specific in identifying a full stomach but only moderately reliable in identifying an empty one. Best results (sensitivity S + 86%, specificity S- 70%, accuracy A+ 78%) were achieved only after water ingestion with the patient in the RLD position. We conclude that bedside ultrasound is of only limited value for determining prandial states in the ED setting.

Emergency Medical Services↗

MRI is nondiagnostic in cervical spine imaging of the helmeted football player with shoulder pads.

BACKGROUND: It is currently recommended that helmet and shoulder pads remain in place during the initial clinical and radiographic evaluation of the helmeted athlete with a potential cervical spine injury. The objective of this prospectively designed, single-subject study was to determine whether MRI may play a role in the initial evaluation and management of the helmeted football player with a cervical spine injury. METHODS: One male athlete was fitted using equipment (football helmet [Riddell], shoulder pads [Douglas]) worn during the collegiate season at Lehigh University. Standard MRI using a routine clinical 0.7 T high field open MRI scanner (GE Signa System, Milwaukee, WI) was employed for the evaluation using standard clinical parameters (sagittal T1, fast spin echo [FSE] T2, STIR, and axial FSE T2 series). A single board-certified, fellowship-trained neuroradiologist reviewed all series. Studies were evaluated for image clarity and diagnostic capability in this clinical setting. RESULTS: All standard MRI series were of extremely limited quality, even using sequences and slice selection designed to minimize artifact associated with metals (FSE T2-weighted series). When all MRI series were reviewed as a whole, sufficient evidence was not available to allow clinical decision making. CONCLUSIONS: The amount and type of metal within the standard football helmet and shoulder pads result in sufficient field inhomogeneity and SKEW artifact to preclude adequate evaluation of the cervical structures, rendering MRI evaluation in this setting not clinically useful. This study shows that current MRI techniques play no role in the clearance of the cervical spine (with currently available brands of helmet and shoulder pads in place) without prior equipment removal or manipulation.

Artifacts↗

Dielectrophoretic cell separation and gene expression profiling on microelectronic chip arrays.

Cell membrane dielectric properties of five different cultivated cell lines and human peripheral blood mononuclear cells (PBMC) were determined from dielectrophoretic crossover frequency measurements on a 5 x 5 microelectronic chip array. Based on distinct dielectric property differences between individual cell types, efficient cell separations were achieved by dielectrophoresis on this 5 x 5 array, which included separation of monocytic cells (U937) or human T cell leukemia virus type 1 (HTLV-1) tax-transformed cells (Ind-2) from PBMC, as well as separation of neuroblastoma cells (SH-SY5Y) from glioma cells (HTB). The purity of dielectrophoretically separated cells can be greater than 95%. Expression profiles of IL-1, TNF-alpha, and TGF-beta genes for U937 cells mixed with PBMC before and after the separation were determined by a means of electric field-facilitated hybridization on a 10 x 10 microelectronic chip array. By using the expression levels of pure U937 cells as a control, it was shown that the gene expression profiles of the postseparation cells were significantly different from those of the preseparation cell mixtures. The increase in gene expression levels for U937 cells upon lipopolysaccharide induction could be accurately determined only in the postseparation cells, while the preseparation samples masked these changes. Furthermore, by cultivating the separated HTB and SH-SY5Y cells and measuring expression of the stress-related gene c-fos, dielectrophoretic forces were shown to have little effect on cell survival and stress. The presented approach of using microelectronic chip arrays for both cell separation and gene expression profiling provides a great potential for accurate genetic analysis of specific cell subpopulations in heterogeneous samples.

Cell Line↗

Cardiac arrest on the links: are we up to par? Availability of automated external defibrillators on golf courses in southeastern Pennsylvania.

OBJECTIVES: A growing number of golfers are senior citizens, and it may be predicted that the number of golf-related medical emergencies, including the incidence of cardiac arrest, will increase. This study was designed to survey the level of preparedness of golf courses in southeastern Pennsylvania to respond to cardiac arrest among their members. METHODS: A telephone survey of all of the 180 golf courses in the area was conducted to determine their type (public/private), volume in rounds per year, presence of automated external defibrillator (AED) devices, number of employees, and percentage of employees with cardiopulmonary resuscitation (CPR) training. Participants also were asked to estimate the time needed to reach the farthest point on their course in order to estimate a maximum time to the application of an AED device. RESULTS: A total of 131 of 180 golf courses completed the survey (53 private, 78 public) for an overall response rate of 73%. Private courses reported a greater average number of employees with CPR training [private = 9.1, public = 3.6; p = 0.001] and in AED presence [public = 9%, private = 58.5%; p = 0.0001]. Public courses support a higher volume of play than do private courses [public = 32,000, private = 24,000; p = 0.001], yet have far fewer employees [public=25, private=44; p = 0.004]. The longest time necessary to reach the most remote point on the course was between four and five minutes in all courses. Analysis was performed using the Student's t-test and Pearson's Chi-square as appropriate. CONCLUSION: Neither public nor private golf courses are well equipped to respond to cardiac arrest, but outcomes on public courses likely are to be far worse.

Data Collection↗