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Biomedical subjects

A Ettinger

Publications and source records attributed to A Ettinger.

15 recordsLinked to original sources

Rapid multiserotype detection of human rhinoviruses on optically coated silicon surfaces.

BACKGROUND: More than 100 immunologically distinct serotypes of human rhinoviruses (HRV) have been discovered, making detection of surface exposed capsid antigens impractical. However, the non-structural protein 3C protease (3Cpro) is essential for viral replication and is relatively highly conserved among serotypes, making it a potential target for diagnostic testing. The thin film biosensor is an assay platform that can be formatted into a sensitive immunoassay for viral proteins in clinical specimens. The technology utilizes an optically coated silicon surface to convert specific molecular binding events into visual color changes by altering the reflective properties of light through molecular thin films. OBJECTIVE: To develop a rapid test for detection of HRV by developing broadly serotype reactive antibodies to 3Cpro and utilizing them in the thin film biosensor format. STUDY DESIGN: Polyclonal antibodies to 3Cpro were purified and incorporated into the thin film assay. The in vitro sensitivity, specificity and multiserotype cross-reactivity of the 3Cpro assay were tested. Nasal washes from naturally infected individuals were also tested to verify that 3Cpro was detectable in clinical specimens. RESULTS: The 3Cpro assay is a 28-min, non-instrumented room temperature test with a visual limit of detection of 12 pM (picomolar) 3Cpro. In terms of viral titer, as few as 1000 TCID(50) equivalents of HRV2 were detectable. The assay detected 45/52 (87%) of the HRV serotypes tested but showed no cross-reactivity to common respiratory viruses or bacteria. The thin film assay detected 3Cpro in HRV-infected cell culture supernatants coincident with first appearance of cytopathic effect. Data are also presented demonstrating 3Cpro detection from clinical samples collected from HRV-infected individuals. The assay detected 3Cpro in expelled nasal secretions from a symptomatic individual on the first day of illness. In addition, 9/11 (82%) concentrated nasal wash specimens from HRV infected children were positive in the 3Cpro test. CONCLUSION: We have described a novel, sensitive thin film biosensor for rapid detection of HRV 3Cpro. This test may be suitable for the point of care setting, where rapid HRV diagnostic test results could contribute to clinical decisions regarding appropriate antibiotic or antiviral therapy.

3C Viral Proteases↗

Biochemical characterization of alpha-ketooxadiazole inhibitors of elastases.

A series of alpha-ketooxadiazole compounds was prepared and evaluated in vitro as potential inhibitors of human neutrophil elastase (HNE), proteinase-3 (PR-3), and porcine pancreatic elastase (PPE). Several compounds have been found to be very potent, fast, reversible, and selective inhibitors of HNE with Ki values below 100 pM. The highest kon value exceeded 10(7) M(-1) s(-1). Some alpha-ketooxadiazoles were also very effective against PR-3 and PPE with Ki values in the range of 5(-10) nM and 0.1(-2) nM, respectively. The two rings, 1,2,4- and 1,3,4-oxadiazole, are amenable to substitutions, extending the P' side of the inhibitor and allowing additional binding interactions at S' subsites of the enzyme. Nonpeptidic HNE inhibitors containing the oxadiazole heterocycle displayed promising oral bioavailability.

Cathepsin G↗

A new optical immunoassay for detection of S-100B protein in whole blood.

BACKGROUND: S-100B is a protein mainly found in astroglial cells and only detected to a low level in blood. Serum levels of S-100B increase in patients with acute brain injuries. The aim of this study was to establish feasibility of a new Optical ImmunoAssay ([OIA], Bio-Star, Inc, Boulder, CO) test for determination of S-100B in blood. METHODS: We have developed a new, rapid, and sensitive OIA test to identify elevated levels of S-100B in whole blood. The OIA test for S-100B combines monoclonal antibodies specific for the B-subunit of S-100 with OIA thin film technology. Each sample was tested for S-100B by the OIA method and a commercially available immunoluminometric assay. Blood samples were drawn serially from 9 patients undergoing coronary artery bypass graft surgery and during the early postoperative period. RESULTS: The OIA test determination of S-100B protein correlated with immunoluminometric assay data (r = 0.8) with a detection limit of 0.25 ng/mL. CONCLUSIONS: The sensitivity and feasibility of this rapid assay may be suitable for rapid evaluation of S-100B in urgent care settings (surgery, intensive care units, or emergency room).

Aged↗

Contralateral coronoid process bone grafts for orbital floor reconstruction: an anatomic and clinical study.

PURPOSE: This study compares the contour of the coronoid process with the orbital floor using skulls and shows the use of this bone as a graft for orbital floor reconstruction. METHODS: Measurements and contour evaluations of the orbital floor and the contralateral mandibular coronoid process (12 right orbital floors with the lateral surface of the left coronoid process and 12 left orbital floors with the lateral surface of the right coronoid processes) were made in 24 dried adult human skulls (age, race, gender unknown) to assess the feasibility of using the mandibular coronoid process for orbital floor reconstruction. Applying the findings of this study, eight patients who had sustained either an isolated orbital floor blowout fracture (n = 2) or orbital floor compromise with an associated zygomatic bone fracture (n = 6) were treated by using their contralateral coronoid process for repair of the orbital floor. RESULTS: Anatomic Study: Measurements and contour comparisons of the right orbital floor with the left lateral cortex of the coronoid process in 12 skulls and the left orbital floor with the right lateral cortex of the coronoid process in the another 12 skulls showed a close match in contour and demension. CLINICAL STUDY: Although minimal trimming of the peripheral bony margins and medial coronoid cortical plate was needed, none of the grafts required recontouring of their lateral cortical surface in the eight patients. Postoperative radiographic studies showed a correct anatomic contour of the orbital floor. A 1-year follow-up of each patient showed no occurrence of diplopia, enophthalmia, muscle entrapment, or infection. All eight patients had transient (1 to 2 weeks) trismus. CONCLUSION: Based on the anatomic studies and clinical results, the coronoid process makes an excellent donor graft site for reconstruction of orbital floor deformities.

Adult↗

The Cardiac Arrhythmia Suppression Trial: Implications for nursing practice.

BACKGROUND: Care of patients with ventricular arrhythmia after myocardial infarction requires careful nursing management, including assisting with arrhythmia monitoring and testing. Because ventricular premature depolarization is a known risk factor for sudden cardiac death, it was hypothesized that the suppression of asymptomatic or mildly symptomatic ventricular premature depolarization would improve survival in these patients. OBJECTIVE: To review the Cardiac Arrhythmia Suppression Trial findings and provide implications for nursing practice for patients after myocardial infarction. METHODS: The Cardiac Arrhythmia Suppression Trial was a multicenter, randomized, placebo-controlled trial designed to determine whether the suppression of ventricular premature depolarizations in postmyocardial infarction patients would improve survival. Three class I antiarrhythmic drugs were used: encainide, flecainide, or moricizine. Patients for whom the drug suppressed their arrhythmia 80% or more were randomly assigned to that drug and dose or its matching placebo and were followed every 4 months (main study). Patients with 1% to 79% suppression were randomly assigned to the drug or its placebo that best treated their arrhythmia and followed every 4 months. RESULTS: Suppression of asymptomatic or mildly symptomatic ventricular premature depolarization in patients using encainide, flecainide, or moricizine failed to improve patient survival and was even harmful in some cases. CONCLUSIONS: Our results showed that in the absence of effective antiarrhythmic drug therapy, supportive nursing care and arrhythmia monitoring is important until appropriate therapy for the management of these arrhythmias in patients who have had a myocardial infarction can be found. Clinical trials are essential to provide an evaluation of therapies and direction for further studies, as well as a basis for practicing clinicians.

Aged↗

Ionic modulation of triethyllead neurotoxicity in cerebellar granule cell culture.

While the molecular mechanism underlying triethyllead (TEL) neurotoxicity is unknown, we hypothesize that triethyllead mediates an accelerated Cl-/OH exchange across neuronal membranes leading to prolonged depolarization and neuronal cell injury. As a test of this hypothesis we have investigated the effect of external ion modulation on triethyllead neurotoxicity in cerebellar granule cell culture. Cultures were prepared from neonatal rats and used 10-20 days in vitro. Cytotoxicity was assessed by lactate dehydrogenase (LDH) release and trypan blue exclusion. A slow, dose-dependent (1-30 microM TEL) release of LDH occurred after a variable latent period dependent upon [TEL]. External replacement of [Cl-]e by Na isothionate dramatically shifted the dose response curve to the left reflecting an accelerated stimulation of LDH release, while replacement of extracellular [Na+]e with equimolar choline chloride had a minimal protective effect. Similarly, high [Mg2+]e or low [Ca2+]e did not protect or potentiate TEL cytotoxicity. The low [Cl-]e accelerated TEL cytotoxicity was dependent on medium pH: alkaline pH potentiated the cytotoxicity. Low [Cl-]e had no significant effect on culture ATP over 5 hrs. ATP reduction was markedly stimulated by TEL in low Cl- medium in contrast to the minimal decline in [ATP] in the control medium. The reduction of ATP in the low [Cl-]e medium occurred prior to LDH or trypan blue staining release confirming that such reduction in [ATP] was not secondary to cell damage. Substituting K sulfate or Na sulfate for the Cl(-)-free medium revealed marked loss of ATP without LDH release in control and TEL supplemented cultures. These observations provide supporting evidence for the role of an abnormal Cl- flux in mediating TEL-induced neurotoxic injury. Specifically, the membrane depolarization is proportional to the gradient imposed by Cl- efflux/OH influx, stimulated by low [Cl-]e. The rapid loss in ATP appeared early, was not a secondary reflection of neuronal damage but a result of a combination of increased ion flux at the plasma membrane, stimulation of Na+/K+ ATPase and direct TEL-induced inhibition of mitochondrial oxidative phosphorylation.

Adenosine Triphosphate↗

Using observational information in planning and implementation of field studies with children as subjects.

Children have been one of the least-studied populations for estimating environmental exposure, even though they are cited as a sensitive subgroup for diseases derived from environmental exposure. This trend appears to be changing as more studies are conducted with children as subjects. It consequently becomes increasingly important to gather and use observational data in all phases of the study. Observational data are the key for both defining the pathway of exposure and for assessing effectiveness of the data-collection protocols. Obtaining quality data from a study involving children requires: efficient use of observational data, collection of meaningful personal and microenvironmental samples, linkage of observational data to the collected samples, and personnel trained to work with children using pilot-tested protocols. Although all of these help to ensure the quality of the data, the utility of the data is often determined by observational feedback from those who collected it. Laboratory-derived protocols should be living documents and observations from the field should be used to modify the data-collection methods when practical.

Child↗

Edema associated with long-term valproate therapy.

Scattered reports of facial and limb edema have been reported, predominantly in the context of valproate (VPA)-induced hepatic injury. We report seven patients with edema associated with long-term VPA therapy in the absence of hepatic disease.

Adolescent↗

Hygiene- and food-related behaviors associated with blood lead levels of young children from lead-contaminated homes.

Exposures associated with blood lead levels greater than 40 micrograms/dL in young children who live in lead-contaminated homes have been well documented. As the action level for lead is reduced, activities that contribute to lower levels of lead exposure must be identified. A child's eating habits and related hygiene behaviors are major hand-to-mouth activities that have been largely overlooked in the study of activities contributing to lead ingestion. To examine this subject, a survey questionnaire for caretakers of young children was developed. The objective of the questionnaire was to characterize food-related activities of young children and to identify behavioral indicators of lead exposure. The association between food- and hygiene-related behaviors and blood lead levels among 60 children between 13 and 36 months old with low-to-moderate blood lead levels was examined in homes that had been identified as containing lead in paint and house dust. The participants were enrolled in the Children's Lead Exposure and Reduction Study in Jersey City, New Jersey. Blood lead levels of children 13-24 months old did not differ significantly from those of children 25-36 months of age (10.1 and 11.3 micrograms/dL, respectively). Differences in eating habits and hygiene behaviors were found for the two age groups. Bivariate analyses found that the primary behavioral indicators of blood lead levels were determined by whether the child prepared his/her own food and whether the child ate food that had been on the floor. This factor was dependent on age. Children 13-24 months old had significantly elevated blood lead levels if these behaviors exhibited. No significant differences were found, however, for children 25-36 months old. Several food-related habits were also associated with blood lead levels. Eating hamburgers, doughnuts, peanut butter and jelly sandwiches, and cold cuts were associated with elevated blood lead levels in 13-24-month-old children, while eating vitamins, raw vegetables, and yogurt were associated with lower blood lead levels in this age group. For children 25-36 months old, eating hamburgers and peanut butter and jelly sandwiches was associated with elevated blood lead levels, while yogurt consumption was associated with lower blood lead levels.

Age Factors↗