Urine Dipstick as a Screening Test for Serum Creatinine Elevation in Emergency Department Patients with Severe Hypertension

OBJECTIVE: Patients presenting to the emergency department (ED) with severe hypertension require assessment for acute end-organ damage. Serum creatinine (SCr) measurement is routinely recommended to detect renal dysfunction. The authors assessed the utility of the urine dipstick test in screening for acute SCr elevation in this population. METHODS: The authors performed a prospective study of adult ED patients with diastolic blood pressures > or = 115 mm Hg that persisted for > or = 30 minutes or necessitated emergent treatment. Excluded were menstruating and pregnant women and patients with urinary infection, trauma, or dialysis dependence. Patients reporting a history of renal disease were excluded if the SCr was abnormal and no baseline value was available. Each subject had an SCr and urine dipstick test. The authors examined the performance of the dipstick in identifying an elevated SCr, defined as SCr > 1.2 mg/dL or > 25% above baseline. RESULTS: Of 143 patients, 42 had SCr > 1.2 mg/dL. Eighteen reported prior renal disease but had an SCr that was normal or < or = 25% above baseline. The remaining 24 subjects comprised the elevated SCr group. The presence of either proteinuria or hematuria on dipstick identified these patients with 100% sensitivity and 29.7% specificity. Specificity rose to 42.4% without loss of sensitivity when an abnormal dipstick was defined as hematuria or > or = 1+ proteinuria. CONCLUSIONS: The urine dipstick may be an effective screening test for SCr elevation in patients with severe hypertension. A restrictive definition of an abnormal dipstick would identify all patients with elevated SCr and substantially reduce the number of SCr assays necessary.     

Enteric coating of fenoprofen calcium reduces gastrointestinal microbleeding

The effects of plain and enteric-coated fenoprofen calcium (Nalfon, Dista, Indianapolis, Ind.) on gastrointestinal microbleeding were studied in 32 normal male volunteers in a randomized, open-label, parallel trial at two inpatient research facilities. A 1-week placebo (baseline) period preceded 2 weeks of fenoprofen therapy (enteric coated or plain, 600 mg q.i.d.). Fecal blood loss was measured by 51Cr-tagged erythrocyte assay and averaged over days 4 to 7 (baseline) and 11 to 14 and 18 to 21 (active therapy). At one center gastrointestinal irritation was evaluated endoscopically before and after active therapy. Endoscopy showed both formulations to cause mucosal damage not evident by subject-reported symptoms. Four of the 16 subjects developed asymptomatic duodenal ulcers. Mean daily fecal blood loss was significantly lower (P = 0.03) with enteric-coated (mean +/- SD, 1.104 +/- 0.961 ml/day) than with plain fenoprofen calcium (mean +/- SD, 1.686 +/- 0.858 ml/day), suggesting that tolerance of fenoprofen can be improved with administration in an enteric-coated form.     

Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects

TGF-betas play diverse and complex roles in many biological processes. In tumorigenesis, they can function either as tumor suppressors or as pro-oncogenic factors, depending on the stage of the disease. We have developed transgenic mice expressing a TGF-beta antagonist of the soluble type II TGF-beta receptor:Fc fusion protein class, under the regulation of the mammary-selective MMTV-LTR promoter/enhancer. Biologically significant levels of antagonist were detectable in the serum and most tissues of this mouse line. The mice were resistant to the development of metastases at multiple organ sites when compared with wild-type controls, both in a tail vein metastasis assay using isogenic melanoma cells and in crosses with the MMTV-neu transgenic mouse model of metastatic breast cancer. Importantly, metastasis from endogenous mammary tumors was suppressed without any enhancement of primary tumorigenesis. Furthermore, aged transgenic mice did not exhibit the severe pathology characteristic of TGF-beta null mice, despite lifetime exposure to the antagonist. The data suggest that in vivo the antagonist may selectively neutralize the undesirable TGF-beta associated with metastasis, while sparing the regulatory roles of TGF-betas in normal tissues. Thus this soluble TGF-beta antagonist has potential for long-term clinical use in the prevention of metastasis.     

Identification of a new shared HLA-A2.1 restricted epitope from the melanoma antigen tyrosinase

Tyrosinase has many advantages as a target antigen for the immunotherapy of patients with melanoma because it is expressed in nearly all melanoma specimens with a high degree of cellular homogeneity, and its distribution in normal tissues is limited to melanocytes. To broaden our ability to direct cellular immune responses against this protein, we pursued an investigation to identify new shared human leukocyte antigen (HLA)-A2.1 restricted epitopes from tyrosinase. Peptides were synthesized that fit a permissive HLA-A2.1 binding motif and did not span common sites of polymorphism. The binding affinity of each peptide to HLA-A2.1 relative to a standard peptide with intermediate binding affinity was evaluated in a competitive inhibition assay. Twelve peptides were selected that had binding affinities within 80% of that of the standard peptide, and these were used to stimulate peripheral blood mononuclear cells (PBMC) in vitro from three HLA-A2.1+ patients with metastatic melanoma. Cytotoxic T lymphocytes that specifically recognized peptide-pulsed target cells as well as HLA-A2.1+ tyrosinase+ melanoma cells were raised from one patient with tyrosinase:8-17 (CLLWSFQTSA). To evaluate further the immunogenicity of this peptide, PBMC from 23 HLA-A2.1+ patients were stimulated in vitro with tyrosinase:8-17. Eleven bulk T-cell cultures demonstrated specific peptide recognition, and six of these also recognized HLA-A2.1+ tyrosinase+ melanoma cells. These data suggest that tyrosinase:8-17 may be clinically useful for the treatment of patients with melanoma.     

Detection and quantitation of fetal maternal hemorrhage utilizing an enzyme-linked antiglobulin test

Existing methods to evaluate fetal-maternal hemorrhage depend upon red blood cell agglutination or blood film elution techniques. These tests are insensitive and difficult to quantitate and reproduce. An enzyme-linked antiglobulin test was evaluated to determine its suitability for clinical testing of postpartum candidates for Rh immune globulin administration. Prepared mixtures of Rh positive fetal and Rh negative adult red blood cells approximating fetal maternal hemorrhage ratios of 0-2.0 percent were studied. In 43 assays, the enzyme-linked antiglobulin test consistently detected Rh positive fetal red blood cells in the 0.5 and 0.25 percent mixtures representing a 25 ml and a 12.5 ml hemorrhage, respectively, in a 70-kg woman. The 0.125 percent red blood cell suspension was positive in 85 percent of the assays and the 0.0625 percent suspension was positive in 56 percent of the tests. Agglutination testing by Du variant technique failed to detect 25 percent of the 0.5 percent mixtures. Only 45 percent of tests with the Rh immune globulin crossmatch detected the 0.5 percent mixture. A modified Kleihauer-Betke procedure was as sensitive, but less reproducible than the enzyme-linked antiglobulin test. Forty-seven Rh immune globulin candidates were studied to assess the quantity of fetal maternal hemorrhage. Fourteen patients (29.8%) had detectable Rh positive red blood cells by enzyme-linked antiglobulin tests but all hemorrhages were less than 12 ml; agglutination tests did not detect any fetal red blood cells. We conclude that the enzyme-linked antiglobulin test is a simple, sensitive, and objective procedure for detecting small amounts of Rh positive red blood cells in Rh negative blood and should be applicable to clinical testing of post-partum Rh immune globulin candidates.     

Digital photography: a primer for pathologists

The computer and the digital camera provide a unique means for improving hematology education, research, and patient service. High quality photographic images of gross specimens can be rapidly and conveniently acquired with a high-resolution digital camera, and specialized digital cameras have been developed for photomicroscopy. Digital cameras utilize charge-coupled devices (CCD) or Complementary Metal Oxide Semiconductor (CMOS) image sensors to measure light energy and additional circuitry to convert the measured information into a digital signal. Since digital cameras do not utilize photographic film, images are immediately available for incorporation into web sites or digital publications, printing, transfer to other individuals by email, or other applications. Several excellent digital still cameras are now available for less than 2,500 dollars that capture high quality images comprised of more than 6 megapixels. These images are essentially indistinguishable from conventional film images when viewed on a quality color monitor or printed on a quality color or black and white printer at sizes up to 11x14 inches. Several recent dedicated digital photomicroscopy cameras provide an ultrahigh quality image output of more than 12 megapixels and have low noise circuit designs permitting the direct capture of darkfield and fluorescence images.There are many applications of digital images of pathologic specimens. Since pathology is a visual science, the inclusion of quality digital images into lectures, teaching handouts, and electronic documents is essential. A few institutions have gone beyond the basic application of digital images to developing large electronic hematology atlases, animated, audio-enhanced learning experiences, multidisciplinary Internet conferences, and other innovative applications. Digital images of single microscopic fields (single frame images) are the most widely utilized in hematology education at this time, but single images of many adjacent microscopic fields can be stitched together to prepare "zoomable" panoramas that encompass a large part of a microscope slide and closely simulate observation through a real microscope. With further advances in computer speed and Internet streaming technology, the virtual microscope could easily replace the real microscope in pathology education. Later in this decade, interactive immersive computer experiences may completely revolutionize hematology education and make the conventional lecture and laboratory format obsolete. Patient care is enhanced by the transmission of digital images to other individuals for consultation and education, and by the inclusion of these images in patient care documents. In research laboratories, digital cameras are widely used to document experimental results and to obtain experimental data.     

External validation of compliance to perfusion quality indicators

PURPOSE: There exists a significant gap between the expected and delivered level of quality received in America's hospitals. As a result, clinical outcomes of critical services such as coronary artery bypass graft (CABG) surgery have received unparalleled scrutiny. Medical information technology companies like Solucient and insurance carriers such as Blue Cross of California have identified and published a list of hospitals that demonstrate superior quality and patient outcomes for CABG procedures. These 'benchmark' programs serve as a reminder that closing the quality gap is possible. Unfortunately, none of these rankings (report cards) provide programs that fail to achieve benchmark status with detailed information on the processes or methods necessary to improve performance. METHOD: After identifying hospitals within the Fresenius Medical Care Extracorporeal Alliance (FMCEA) system that were judged as top performers (benchmark programs) by either Solucient ('100 Top Cardiovascular Hospitals', Evanston, IL 60201) or Blue Cross of California ('Centers of Expertise', Newbury Park, CA 91320), 12 months of continuous collection of CPB-related quality indicator data were analyzed for compliance to the FMCEA evidence-based Quality Indicator Program (QIP). A comparison of compliance to the FMCEA CPB indicators was made between the benchmark FMCEA hospitals and the FMCEA peer group hospitals. RESULTS: Seven CPB process indicators were compared: 1) lowest sustained mean arterial pressure, 2) lowest sustained cardiac index, 3) lowest sustained mixed venous oxygen saturation, 4) lowest sustained hematocrit, 5) lowest activated clotting time, 6) highest sustained arterial blood temperature and 7) average sodium bicarbonate administered. Analysis of hospitals in the FMCEA system designated by Blue Cross of California as 'Centers of Expertise' revealed statistically significantly greater compliance (p < 0.05) in all but one CPB indicator. Hospitals in the FMCEA system designated by Solucient's '100 Top Cardiovascular Hospitals' listing revealed statistically significantly greater compliance to all but three CPB quality indicators. CONCLUSIONS: Successful compliance with the majority of FMCEA CPB process indicators correlates with external recognition from two report card systems demonstrating superior hospital performance. Analysis of compliance to process indicators may provide useful guidelines to improve the standard of care in CABG surgery in many hospitals.     

Validation of the 2001 American Thoracic Society criteria for severe community-acquired pneumonia

STUDY OBJECTIVE: Ewig et al. proposed a new definition of severe community-acquired pneumonia in 1999, which was adopted by the American Thoracic Society in 2001. We evaluated this definition in an independent population of emergency department patients. DESIGN: We compared the 2001 American Thoracic Society definition of severe community-acquired pneumonia using emergency department data to intensive care unit (ICU) admission, use of mechanical ventilation, and administration of vasopressors. SETTING: LDS Hospital, a tertiary care, university-affiliated hospital with 520 total beds and 68 ICU beds in Salt Lake City, UT. PATIENTS: We studied 980 consecutive emergency department patients with a radiographically confirmed diagnosis of pneumonia between June 1995 and June 1999. Of these patients, 498 were admitted to the hospital, immunocompetent, and without a "do-not-resuscitate" order within 24 hrs of admission. MEASUREMENTS AND MAIN RESULTS: Forty-seven patients met the criteria for severe community-acquired pneumonia in the emergency department and were admitted to the ICU. Three hundred eighty patients did not meet the criteria and were admitted to a hospital unit. Nineteen patients met the definition but were admitted to a hospital unit; only one required subsequent ICU admission. Two of the 19 died after a do-not-resuscitate order was entered >24 hrs after admission; the remainder recovered. Fifty-two patients were triaged to the ICU but did not initially meet the definition of severe pneumonia. Sixteen of these 52 patients required mechanical ventilation, 13 of the 16 within 24 hrs of admission to the ICU. The sensitivity for the 2001 American Thoracic Society definition in our population was 44%, specificity was 95%, positive predictive value was 71%, and negative predictive value was 88%. CONCLUSION: The 2001 American Thoracic Society definition of severe community-acquired pneumonia had high specificity but lower sensitivity in our population compared with the derivation population. Additional factors not reflected in the definition may contribute to ICU admission and the need for mechanical ventilation.