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Biomedical subjects

S J Weiss

Publications and source records attributed to S J Weiss.

At least 91 records · Page 5Linked to original sources

Molecular cloning of human cathepsin O, a novel endoproteinase and homologue of rabbit OC2.

A 1670-bp cDNA coding for a novel human cysteine protease has been isolated from a monocyte-derived macrophage cDNA library. This cDNA predicts a 329-amino acid preprocathepsin with more than 50% identity to both human cathepsin S and cathepsin L and 94% identity to a rabbit cDNA, termed OC2, recently isolated from osteoclasts. Based on its high homology to OC2, we have named the human enzyme cathepsin O. Cathepsin O mRNA was identified as a single approximately 1.7 kb transcript in cultures of 15-day-old monocyte-derived macrophages, but was not expressed in human monocytes or alveolar macrophages. When transfected into COS-7 cells, cathepsin O displayed potent endoprotease activity against fibrinogen at acid pH. This novel endoprotease may play an important role in extracellular matrix degradation.

Amino Acid Sequence↗

LAT (lidocaine-adrenaline-tetracaine) versus TAC (tetracaine-adrenaline-cocaine) for topical anesthesia in face and scalp lacerations.

The study objective was to compare the topical anesthetic LAT (4% lidocaine, 1:2,000 adrenaline, 1% tetracaine) to TAC (0.5% tetracaine, 1:2,000 adrenaline, 11.8% cocaine) for efficacy, adverse effects, and costs. The study design was a randomized, prospective, double blind clinical trial set in an inner-city emergency department with an emergency medicine residency program. Adults with linear lacerations of the face or scalp were eligible for inclusion in the study. Patients had lacerations anesthetized with topical TAC or LAT according to a random numbers table. A total of 95 patients were included in the study with 47 receiving TAC and 48 receiving LAT. Patients stated the number of sutures causing pain and patients and physicians rated the overall pain of suturing using a standard visual analog scale (VAS). The power of the study to determine a ranked sum difference of 15 was 0.8. Visual analog scale results and number and percentage of sutures causing pain were compared using Wilcoxon's Rank Sum Test. According to patients, the percentage of sutures causing pain was significantly fewer for LAT than TAC (P = .036, Interquartile Range 0.13 to 0.0 for LAT, 0.25 to 0 for TAC). Physicians found LAT statistically more effective than TAC (P = .0093, Interquartile Range 1 to 0 for LAT, 2 to 0 for TAC) but patients did not report a difference (P = .266, Interquartile Range 1 to 0 for both LAT and TAC). Our cost per application was $3.00 for LAT compared to $35.00 for TAC. Follow-up was accomplished in 91 of 95 patients (95%) with no reported complications for either medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Syphilis screening in out-of-hospital care.

To estimate the rates of syphilis infection in inner-city patients managed by prehospital providers, a convenience sampling of prehospital patients who had intravenous lines initiated was screened for syphilis over a nine-month study period from February 1992 through October 1992. In a university-affiliated inner-city emergency department served by a city ambulance company, patients 18 years of age or older transported via ambulance who had had intravenous lines initiated at the scene or en route had a Venereal Disease Research Laboratory (VDRL) and microhemagglutination-Treponema pallidum (MHA-TP) drawn and performed by the state laboratory as a routine serological test. If the results were reactive with no previous history of syphilis recorded in the state registry, the state health department and/or one of the authors of this study contacted the patient for follow-up treatment. Age, race, sex, and diagnostic category (medical, surgical/obstetric, or neuropsychiatric) were recorded. Results were checked with the state syphilis registry. Latent syphilis was defined as a reactive VDRL and MHA-TP with no prior history of infection or record of infection in the state syphilis registry. Chi-squared test was used in statistical analysis for comparisons among ages, races, and sexes, with P > .05 considered significant. Three hundred two subjects 18 years of age and older consenting to a screening VDRL and MHA-TP had serum drawn. Two hundred seventy-nine patients were enrolled in the study after 23 patients were excluded because of improper data collection or insufficient serum collection. There were 174 men (63%) and 105 women (37%), with 73 white (26%) and 199 African-Americans (71%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Art hazards.

The diseases associated with art forms range from trauma (vibration syndrome, flying objects, etc) and heat exposure, to heavy metal and solvent exposure. Specific substances such as ozone, cadmium, and molybdenum have unique diseases associated with them. Sadly, artists may not have the medical knowledge to know how to deal with or avoid hazards. They and their immediate families often may be at risk. Many artists are not educated in what protective gear to use and do not have the money to purchase the specialized equipment for their particular work, or they refuse to wear protective gear because they are uncomfortable in the conditions encountered in the workplace. Education is often required for the use of the protective gear (respiratory, eyewear, contact protection). To make matters worse, artists are poorly protected from toxins. Government regulations are not adequate to protect self-employed artists. Laws regulating children's exposure do not address long-term toxicity. Most artists with acute problems present to the ED first. An awareness of the occupational hazards to which self-employed artists are exposed will prevent the treating physician from overlooking important clues. When an artist presents with unusual symptoms, the physician must get a complete occupational history and must have the patient bring a list or samples of any substances to which he or she has been exposed. In essence, artists are a group of enthusiastic, hardworking people that can be protected by a keen awareness of these basic principles by the treating physician.

Adult↗

Tympanic membrane thermometry in the care of out-of-hospital patients.

STUDY OBJECTIVES: To determine the effectiveness of tympanic membrane (TM) thermometry in the out-of-hospital setting and to characterize the patients with abnormal out-of-hospital temperatures. DESIGN: Prospective, randomized, single-month study. SETTING: Inner city. PARTICIPANTS: Subjects transported by ambulance for whom consent was obtainable. RESULTS: TM probes set to rectal equivalent were assigned to three of the ambulance units of the local health department on randomly selected shifts during August 1992, one half at night and one half during the day. Simultaneous left and right ear temperatures at the scene and at the hospital, ambient temperatures, and patient's hospital temperatures were recorded. Other data recorded included each patient's mental status, activity level, and environment temperature. Paramedics noted whether they suspected a temperature problem before using the probe and whether any treatment was directed toward the patient's temperature. Regression, bias analysis, and chi 2 testing were performed; P was considered significant if it was less than .05. Right and left ear TM temperatures were correlated both at the scene and at the hospital (r = .91 and .92, respectively). TM temperatures and hospital temperatures were also correlated (r = .83 for right ear and .78 for left ear). Evaluation of agreement indicated that TM and hospital methods were equal, with a bias of -0.55 degrees F for oral and +0.66 degrees F for rectal temperatures. Thirty-two subjects (17%) were hyperthermic at the scene; of these, 9 of 32 (28%) were suspected before use of the probe. The paramedics initially treated 5 of the 9 suspected to have a temperature-related problem before using the probe and none of the 23 who were not suspected before using the probe (chi 2, P < .001). CONCLUSION: The TM probe functioned well despite a month of vigorous handling. Temperature correlation with the gold standard and between ears was acceptable in this setting. Presence of the probe did not help with the management of hyperthermic patients in this study.

Adolescent↗

Hydrolytic inactivation of a breast carcinoma cell-derived serpin by human stromelysin-3.

To elucidate structure-function relationships of stromelysin-3, a putative matrix metalloproteinase originally identified at the tumor-stromal cell interface in breast carcinomas, the human cDNA was expressed in mammalian cells, and its products were isolated and characterized. In stably transfected cells, stromelysin-3 was recovered as a complex mixture of species ranging in size from approximately 20 to 65 kDa. Among these products, a major 45-kDa species with an N terminus of Phe98 and an intact C-terminal domain was identified as a true endopeptidase on the basis of its ability to cleave the bait region of alpha 2-macroglobulin between Phe684 and Tyr685, a site identical to that recognized by stromelysin-1. However, unlike stromelysin-1 or other members of the matrix metalloproteinase family, the mature form of stromelysin-3 was unable to hydrolyze a range of extracellular matrix molecules associated with either the basement membrane or interstitium. To probe for alternate substrates among tumor cell-derived products, purified stromelysin-3 was incubated with [35S]methionine-labeled medium conditioned by the breast cancer cell line, MCF-7. Under these conditions, a single, tumor cell-derived protein was hydrolyzed as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Following anion-exchange chromatography and preparative gel electrophoresis, the stromelysin-3 substrate was identified by N-terminal sequencing as the serine proteinase inhibitor, alpha 1-proteinase inhibitor. Further studies demonstrated that stromelysin-3 rapidly destroyed the antiproteolytic function of alpha 1-proteinase inhibitor by cleaving the antiproteinase at a distinct site between Ala350 and Met351 within the reactive-site loop. Together, these data not only demonstrate that human stromelysin-3 acts as a powerful endopeptidase with a restricted substrate specificity distinct from all other matrix metalloproteinases, but also serve to identify serine proteinase inhibitors as potential physiologic targets at sites of extracellular matrix remodeling.

Amino Acid Sequence↗

Oxidative dissociation of human alpha 2-macroglobulin tetramers into dysfunctional dimers.

Human alpha 2-macroglobulin is a broad-spectrum, homotetrameric antiproteinase that can maximally bind up to two proteinase molecules in a ternary complex. Proteinases cleave the inhibitor within a peptide stretch termed the bait region and induce the emergence of internal thiol esters whose nucleophilic scission precede a major conformational change which entraps enzymes within molecular cages. In a previous study, leukocyte-generated hypohalous acids and N-haloamines were identified as the first examples of physiologically relevant inactivators of the antiproteolytic activity of alpha 2-macroglobulin (Reddy, V. Y., Pizzo, S. V., and Weiss, S. J. (1989) J. Biol. Chem. 264, 13801-13809), but the mechanisms whereby the oxidants damaged the inhibitor remained undefined. We now demonstrate that N-chloramines (RNCl) destroy the antiproteolytic activity of alpha 2-macroglobulin in an unusual biphasic process that results in the formation of inactive alpha 2-macroglobulin half-molecules. In the first phase, 8 eq of RNCl reacted with each alpha 2-macroglobulin subunit to generate a partially oxidized antiproteinase containing 8 methionyl sulfoxide residues/monomer. Structure-function analyses demonstrated that the oxidized inhibitor retained its homotetrameric structure as well as its ability to entrap proteinases. In marked contrast, the oxidation of an additional 6 methionyl residues and a single tryptophanyl residue fractured the alpha 2 M homotetramer across its non-covalent axis into two pairs of disulfide-linked dimers. Despite the fact that the oxidized dimers displayed normal bait regions whose cleavage by proteinases initiated thiol ester scission, all antiproteolytic activity was lost. Furthermore, the oxidized dimers were unable to undergo the critical conformational changes normally associated with bait region cleavage or thiol ester scission. Together, these results demonstrate that chlorinated oxidants destroy the antiproteolytic activity of alpha 2-macroglobulin by attacking a subset of methionyl and tryptophanyl residues whose oxidation mediates the dissociation of the native homotetramer into conformationally locked dimers.

Amino Acid Sequence↗

Increasing the completion of the durable power of attorney for health care. A randomized, controlled trial.

OBJECTIVE: Wider use of written advance directives may prevent many ethical dilemmas about life-sustaining interventions for patients who have lost decision-making capacity. We investigated whether a simple educational intervention increased patient completion of the durable power of attorney for health care. DESIGN: A randomized, controlled trial. SETTING: A health maintenance organization. SUBJECTS: All patients aged 65 years and older and discharged from a hospital between January 1991 and May 1991 (n = 1101) were randomized to either an intervention group or a control group. INTERVENTION: An educational pamphlet on the durable power of attorney for health care and a durable power of attorney for health care form were mailed to all patients in the intervention group. The control group received conventional care only. MAIN OUTCOME MEASURE: Completion of the durable power of attorney for health care form. RESULTS: There were no significant baseline differences between the intervention group and the control group. Following our intervention, 18.5% of the subjects in the experimental group completed a durable power of attorney for health care form, compared with 0.4% of the control group (P < .0001). CONCLUSIONS: A simple educational intervention significantly increased the completion of the durable power of attorney for health care. Our findings should stimulate further efforts to empower patients to make informed decisions about their health care.

Advance Directives↗

Intracardiac thrombus: a risk of incomplete anticoagulation for cardiac operations.

Mitral valve replacement was performed urgently in a patient with hemorrhagic brain lesions. To decrease the risk of intracranial hemorrhage, cardiopulmonary bypass was performed using a heparin-coated perfusion system and a reduced dose of heparin. The detection of an acute intracardiac thrombus by transesophageal echocardiography during cardiopulmonary bypass exposed a potential hazard of techniques employing reduced systemic anticoagulation for cardiac operations.

Acute Disease↗

Management of difficult coronary sinus rupture.

A technique of handling severe coronary sinus rupture when direct suture repair or pericardial patch techniques have failed is described. A pericardial patch is sewn over the coronary sinus with running 5-0 Prolene suture, and an 8-mm thin-walled Gore-Tex conduit then is constructed between the patch and the right atrium to decompress the repair and allow an alternative route for coronary sinus return to the right atrium.

Aged↗

Effect of out-of-hospital albuterol inhalation treatments on patient comfort and morbidity.

STUDY OBJECTIVE: To determine the effect of the institution of out-of-hospital albuterol treatments for acute asthma on out-of-hospital time intervals emergency department (ED) morbidity. DESIGN: Retrospective chart and ambulance run report review. PARTICIPANTS: All patients who presented with a diagnosis of asthma on the ED record and ambulance run report during 1988 and 1990. RESULTS: Ninety patients treated prior to the routine use of nebulized albuterol (in 1988) and 86 patients treated during the period after the institution of nebulized albuterol (in 1990) were compared. Age, sex, scene and travel times, vital signs, peak expiratory flow rates, length of ED stay, hospitalizations, ED treatment, and mortality were recorded for each patient. Changes over time were determined using a cohort of asthma patients in each year as controls. Severity was recorded as low (less than 3) or high (3 or more) on a modified Fischl index for asthma. Groups were compared by F test, chi 2, or t test with P < .05 considered significant. Because there were differences for admission rates, first-hospital peak expiratory flow rates, and aminophylline use in control groups, the experimental groups could not be compared. No significant difference in travel interval, steroid use, albuterol treatments, or length of ED stay was determined in either the experimental or control group. Scene time (9.7 minutes versus 12.1 minutes) was significantly shorter in 1988 than in 1990 (difference, 2.4 minutes; 95% confidence interval, 0.2 to 4.6; P < .01). The percentage of patients with high initial severity of disease (85% versus 66%; P < .001) and the percentage of patients with first posttreatment peak expiratory flow rates of less than 120 L/min (77% versus 58%; P < .001) were significantly higher in 1988 than in 1990. There was no significant difference in scene time, severity scores, or first posttreatment peak expiratory flow rates in control groups. CONCLUSION: The institution of out-of-hospital use of nebulized albuterol increased scene time and increased first posttreatment peak expiratory flow rates significantly. There was a significant decrease in initial patient severity as measured on the modified Fischl index, although the validity of this index has not been established. It did not affect travel interval, length of stay in the ED, or medication use after ED presentation.

Acute Disease↗

1% lidocaine versus 0.5% diphenhydramine for local anesthesia in minor laceration repair.

STUDY OBJECTIVE: Our previous study demonstrated that 1% diphenhydramine is as effective as 1% lidocaine for anesthesia in minor laceration repair, but that it also is more painful to inject. The purpose of this study was to compare 0.5% diphenhydramine to 1% lidocaine for pain of injection and adequacy of local anesthesia. STUDY DESIGN: Randomized, double-blinded, prospective study from December 1991 through June 1992. SETTING: University-affiliated, urban, inner-city emergency department. PARTICIPANTS: Ninety-eight adults with linear skin lacerations without end-organ involvement were included; 48 received lidocaine and 50 received diphenhydramine. INTERVENTIONS: Wounds were anesthetized with either diphenhydramine or lidocaine according to a random table. Both patients and physicians rated the pain of injection and suturing according to a standard, previously tested, visual analog scale. MEASUREMENTS AND MAIN RESULTS: Patient and physician ratings were ranked without regard to treatment group, and rank sum scores were calculated for each group. General linear models and multivariate analysis of variance were used to analyze the ranked sum scores. The power of the study to detect a ranked sum difference of 15 was 0.8 with P < .05 considered statistically significant. Lidocaine was found to be significantly more effective as a local anesthetic for facial lacerations according to both patients (P < .002) and physicians (P < .004). There was no statistically significant difference between 1% lidocaine and 0.5% diphenhydramine for pain of injection or suturing for all other locations according to both patients and physicians. Overall mean and median scores for injection and suturing with diphenhydramine corresponded to the mild pain category according to patients. CONCLUSION: Although not a replacement for lidocaine, diphenhydramine is a viable alternative for anesthesia in the repair of minor lacerations.

Adult↗

Echocardiographic and hemodynamic indexes of left ventricular preload in patients with normal and abnormal ventricular function.

BACKGROUND: Transesophageal echocardiography (TEE) is used to diagnose hypovolemia despite the lack of validation studies. The objective was to determine the effects of acute graded hypovolemia on TEE and conventional hemodynamic determinants of left ventricular (LV) preload in anesthetized patients with normal and abnormal LV function. METHODS: Determinants of LV preload derived from TEE and hemodynamic monitoring were measured serially in 35 anesthetized cardiac surgical patients without valvular heart disease. Patients were stratified into two groups: those with normal LV function (group 1, n = 17) and those with LV wall motion abnormalities (group 2, n = 13). Patients in groups 1 and 2 were subjected to graded hypovolemia produced by collecting 6 aliquots of blood, each equal to 2.5% of their estimated blood volume (EBV). A third group of patients (group 3, n = 5), not subjected to graded hypovolemia, were studied to test for time-dependent changes. RESULTS: Group 2 had a significantly greater baseline (mean +/- SD) pulmonary artery occlusion pressure (17 +/- 6 vs. 11 +/- 6 mmHg), LV end-diastolic area (23 +/- 5 vs. 18 +/- 4 cm2), LV end-diastolic wall stress (23 +/- 10 vs. 14 +/- 6 x 10(3) dyne.cm-2), and smaller fractional area change (35 +/- 13 vs. 59 +/- 7%). In groups 1 and 2, the LV end-diastolic area, pulmonary artery occlusion pressure, and LV end-diastolic wall stress decreased linearly in response to blood loss in the range of 0-15% of the EBV. No significant changes in the measured parameters occurred in group 3. A significant decrease in the central venous pressure, pulmonary artery occlusion pressure, and LV end-diastolic area was detected in response to a 2.5% EBV deficit (approximately 1.75 ml.kg-1) in groups 1 and 2. The mean change in LV end-diastolic area (0.3 cm2/1.0% EBV deficit) in response to equivalent EBV deficits was the same in groups 1 and 2. In contrast, the mean change in cardiac output and LV end-diastolic wall stress was less in group 2 despite a greater decrease in pulmonary artery occlusion pressure. Compared to group 1, a greater EBV deficit (7.5% to 12.5% vs. 2.5% to 5%) was required in group 2 to cause a significant decrease in the cardiac output, stroke volume, mixed venous oxygen saturation, and LV end-diastolic wall stress. CONCLUSIONS: TEE and hemodynamic determinants of LV preload detected changes in LV function caused by acute blood loss. Acute blood loss caused directional changes in LV end-diastolic area, pulmonary artery occlusion pressure, and LV end-diastolic wall stress even in patients with LV wall motion abnormalities. Changes in LV end-diastolic wall stress, derived from both TEE and hemodynamic measurements corresponded to changes in cardiac output, stroke volume, and mixed venous oxygen saturation that occurred during acute blood loss.

Coronary Artery Bypass↗

Emergency medical services development in the state of Louisiana.

Management of Emergency Medical Services has been sadly forgotten over the years in the state of Louisiana. A new task force which was formed over a year ago is now beginning to formulate a direction for the future of EMS in this state. At its last Annual Meeting, the LSMS adopted a resolution to support the work and decisions made by that task force. The EMS task force pulled together firefighters, emergency medical technicians, ambulance employees, and a group of physicians representing the specialities of trauma, emergency medicine, and pediatrics. Subcommittees were formed to address legislation, licensure, education, medical control, and pediatric issues. Definitive direction for the Bureau of EMS has been formulated with the aid of the task force and its various subcommittees. The LSMS as a whole supports this initiative; however, for it to succeed, the entire membership must understand the importance of EMS to everyone in the state. Good out-of-hospital care will determine whether a person gets early thrombolytic care, whether early defibrillation is available at their sides, and whether their child is treated with "pediatric appropriate" approaches to medical care. The life saved could be important to any one of us. The purpose of this article is to acquaint the membership with what EMS is, what the condition of EMS in Louisiana is, and what the progress of the EMS task force has been.

Education, Medical↗

In vivo suppression of immune complex-induced alveolitis by secretory leukoproteinase inhibitor and tissue inhibitor of metalloproteinases 2.

The pulmonary tree is exposed to neutrophil-derived serine proteinases and matrix metalloproteinases in inflammatory lung diseases, but the degree to which these enzymes participate in tissue injury remains undefined, as does the therapeutic utility of antiproteinase-based interventions. To address these issues, an in vivo rat model was examined in which the intrapulmonary deposition of immune complexes initiates a neutrophil-mediated acute alveolitis. In vitro studies demonstrated that rat neutrophils can release neutrophil elastase and cathepsin G as well as a neutrophil progelatinase, which was subsequently activated by either chlorinated oxidants or serine proteinases. Based on structural homologies that exist between rat and human neutrophil proteinases, rat neutrophil elastase and cathepsin G activities could be specifically regulated in vitro by recombinant human secretory leukoproteinase inhibitor, and rat neutrophil gelatinase activity proved sensitive to inhibition by recombinant human tissue inhibitor of metalloproteinases 2. When either of the recombinant antiproteinases were instilled intratracheally, in vivo lung damage as assessed by increased permeability or hemorrhage was significantly reduced. Furthermore, the coadministration of the serine and matrix metalloproteinase inhibitors almost completely prevented pulmonary damage while effecting only a modest decrease in neutrophil influx. These data support a critical role for neutrophil-derived proteinases in acute lung damage in vivo and identify recombinant human secretory leukoproteinase and recombinant human tissue inhibitor of metalloproteinases 2 as potentially efficacious interventions in inflammatory disease states.

Animals↗