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Biomedical subjects

S J Weiss

Publications and source records attributed to S J Weiss.

At least 55 records · Page 3Linked to original sources
PubMed1999

Characterization of matrix metalloproteinases produced by rat alveolar macrophages.

Evidence presented in the accompanying article (Gibbs, D. F., T. P. Shanley, R. L. Warner, H. S. Murphy, J. Varani, and K. J. Johnson. 1999. Role of matrix metalloproteinases in models of macrophage-dependent acute lung injury: evidence for alveolar macrophage as source of proteinases. Am. J. Respir. Cell Mol. Biol. 20:1145-1154) implicates alveolar macrophage matrix metalloproteinases (MMPs) in two models of acute lung inflammation in the rat. As a prerequisite to understanding which specific MMPs might be involved in the injury and how they might function, it was necessary to know the spectrum of enzymes present. To this end, alveolar macrophages were obtained from normal rat lungs by bronchoalveolar lavage, placed in culture with and without various agonists, and assessed by a variety of techniques for MMPs. The identification process involved characterization by gelatin, beta-casein, and kappa-elastin zymography, with confirmation of identity by Western blot/immunoprecipitation. Message levels of detected MMPs were assessed by Northern blot. Rat alveolar macrophages were found to produce a low constitutive level of MMP-2 (72-kD gelatinase A) that was only modestly upregulated following stimulation with phorbol myristate acetate, bacterial lipopolysaccharide, or immunoglobulin A-containing immune complexes. Although control cells were found to produce little or no MMP-9 (92-kD gelatinase B) or MMP-12 (metalloelastase), both enzymes were markedly upregulated upon stimulation. In the same stimulated macrophages there was little activity against type I collagen (associated with MMP-13 [collagenase-3] on the basis of Western blotting), no activity suggestive of stromelysin or matrilysin, and no measurable secretion of the serine proteinases, elastase and cathepsin G. These data demonstrate the ability of rat alveolar macrophages to elaborate certain MMPs under proinflammatory conditions, consistent with their possible involvement in the progression of acute inflammation.

Animals↗
PubMed1999

Blocking a selective association in pigeons.

Experiment 1 demonstrated for the first time a stimulus-reinforcer interaction in pigeons trained with free-operant multiple schedules of reinforcement. Pigeons that treadle pressed in the presence of a tone-light (TL) compound for food exhibited primarily visual stimulus control on a stimulus-element test, whereas pigeons that avoided shock in TL exhibited auditory control. In Experiment 2, this selective association was blocked in pigeons pretrained with the biologically contingency-disadvantage element of the compound (i.e., tone-food or light-shock) before TL training. When this pretraining preceded compound-stimulus training, control was now auditory in pigeons that treadle pressed for food and was visual in pigeons that avoided shock. Previous attempts at blocking this selective association were unsuccessful in pigeons (LoLordo, Jacobs, & Foree, 1982) but were successful in rats (Schindler & Weiss, 1985). Experiment 2 established that selective associations can be blocked in pigeons when the procedures that were effective with rats were systematically replicated. These results further demonstrate the cross-species generality of an associative attentional mechanism involving a biological constraint on learning in species with different dominant sensory systems.

Animals↗
PubMed1999

Nicardipine intravenous bolus dosing for acutely decreasing arterial blood pressure during general anesthesia for cardiac operations: pharmacokinetics, pharmacodynamics, and associated effects on left ventricular function.

UNLABELLED: The objective of this study was to evaluate the efficacy of nicardipine, a dihydropyridine calcium channel antagonist, administered as an IV bolus dose to acutely decrease arterial pressure in anesthetized cardiac surgical patients. We performed a double-blind, randomized, self-controlled, dose-ranging study in 40 adult cardiac surgical patients to determine the pharmacokinetics and pharmacodynamics of nicardipine 0.25 mg, 0.50 mg, 1.00 mg, and 2.00 mg administered as an IV bolus. Transesophageal echocardiography was used to assess left ventricular preload, afterload, and global systolic function. Plasma nicardipine concentration was measured using high-performance liquid chromatography. Nicardipine selectively decreased arterial pressure in a dose-dependent manner with a maximum response within 100 s and recovery to half the maximum response within 3-7 min without associated changes in heart rate. The decreases in arterial pressure were associated with only small decreases in left ventricular end-systolic wall stress and small increases in global left ventricular systolic function without changes in left ventricular end-diastolic cavity area or cardiac output. The time course for nicardipine bolus was consistent with a two-compartment pharmacokinetic model with rapid redistribution from a small central compartment. IMPLICATIONS: Nicardipine was effective for selectively decreasing arterial blood pressure acutely, but had no effects on ventricular preload or cardiac output. The absence of dose-dependent changes in cardiac output, left ventricular systolic performance, and left ventricular afterload despite significant decreases in arterial pressure suggested that nicardipine had a small negative inotropic action.

Aged↗
PubMed1998

Role of the plasminogen activator and matrix metalloproteinase systems in epidermal growth factor- and scatter factor-stimulated invasion of carcinoma cells.

Normal as well as neoplastic cells traverse extracellular matrix barriers by mobilizing proteolytic enzymes in response to epidermal growth factor (EGF)-EGF receptor (EGFR) or hepatocyte growth factor/scatter factor (SF)-c-Met interactions. The plasminogen activator-plasminogen axis has been proposed to play a key role during cell invasion, but the normal development of plasminogen activator- as well as that of plasminogen-deficient mice supports the existence of alternate proteolytic systems that permit cells to traverse extracellular matrix barriers. To characterize the role that matrix-degrading proteinases play in EGF- or SF-stimulated invasion, a human squamous carcinoma cell line (UM-SCC-1) was triggered atop the matrices of type I collagen or human dermal explants in a three-dimensional culture system. During EGF- or SF-induced invasion, UM-SCC-1 cells expressed urokinase-type plasminogen activator (uPA) and uPA receptor as well as the matrix metalloproteinases (MMPs), membrane-type MMP-1, collagenase 1, stromelysin 1, and gelatinase B. Despite the presence of a positive correlation between uPA receptor-uPA expression and growth factor-stimulated invasion, UM-SCC-1 invasion was not affected by inhibitors directed against the plasminogen activator-plasminogen axis. In contrast, both recombinant and synthetic MMP inhibitors completely suppressed invasion by either EGF- or SF-stimulated cells without affecting either proteinase expression or cell motility across collagen-coated surfaces. These data demonstrate that MMPs, but not the plasminogen activator-plasmin system, can directly regulate the ability of either EGF- or SF-stimulated tumor cells to invade interstitial matrix barriers.

Animals↗
PubMed1998

Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysins.

During angiogenesis, endothelial cells penetrate fibrin barriers via undefined proteolytic mechanisms. We demonstrate that the fibrinolytic plasminogen activator (PA)-plasminogen system is not required for this process, since tissues isolated from PA- or plasminogen-deficient mice successfully neovascularize fibrin gels. By contrast, neovessel formation, in vitro and in vivo, is dependent on fibrinolytic, endothelial cell-derived matrix metalloproteinases (MMP). MMPs directly regulate this process as invasion-incompetent cells penetrate fibrin barriers when transfected with the most potent fibrinolytic metalloproteinase identified in endothelium, membrane type-1 MMP (MT1-MMP). Membrane display of MT1-MMP is required, as invasion-incompetent cells expressing a fibrinolytically active, transmembrane-deleted form of MT1-MMP remain noninvasive. These observations identify a PA-independent fibrinolytic pathway wherein tethered MMPs function as pericellular fibrinolysins during the neovascularization process.

Animals↗
PubMed1998

Extraction and quantification of nicardipine in human plasma.

A novel simple method of extraction, separation, identification and quantification of nicardipine in human plasma samples was completely studied. The human plasma samples were initially purified by solid-phase extraction (SPE) using a C18 cartridge. The extracted samples were separated and nicardipine present in the samples was quantified by high-performance liquid chromatography (HPLC) on a reversed-phase C18 column employing a mobile phase consisting of 60% (v/v) acetonitrile in 0.02 M NaH2PO4 with pH of 6.3 and a variable wavelength UV detector set at 254 nm. The recovery of nicardipine from plasma samples using selective SPE was 91+/-6.0% and had less interfering compounds in the HPLC analysis compared to the use of liquid-liquid (L/L) extraction. In the HPLC analysis, examining the effect of pH values of the mobile phase on the capacity factor (k') of nicardipine revealed a method for selecting a critical k' value of nicardipine to eliminate interfering peaks near the peak specific to the analyte. This method for quantification of nicardipine in human plasma samples was suitable for studying the pharmacokinetic profile of nicardipine administered as an intravenous bolus to cardiac surgical patients.

Antihypertensive Agents↗
PubMed1998

Motivational effects of compounding discriminative stimuli associated with food and cocaine.

In previous experiments, the compounding of two discriminative stimuli associated with the same reinforcer increased rats' responding approximately three-fold, regardless of whether the reinforcer was food, water, cocaine, or shock-avoidance. Compounding a discriminative stimulus associated with food with one associated with water increased responding two-fold. In the present experiment, compounding a discriminative stimulus associated with food with one associated with cocaine increased responding two-fold. These results support the hypothesis that 1) the effects of stimuli associated with reinforcers from the same incentive class (appetitive or aversive) are mutually enhancing, and 2) the combined effects of stimuli associated with two different reinforcers from within the same class are not as strong as those of two stimuli associated with the same reinforcer. These results also suggest that discriminative stimuli associated with non-drug reinforcers may increase the motivation to self-administer cocaine when encountered in combination with drug-related stimuli.

Acoustic Stimulation↗
PubMed1998

Warmed versus room temperature saline solution for ocular irrigation: a randomized clinical trial.

STUDY OBJECTIVE: To test the hypothesis that ocular irrigation with warm saline solution is more comfortable than irrigation with room temperature saline solution in normal volunteers. METHODS: The study was a randomized, single-blind crossover trial, in which each subject received 30 mL warmed and 30 mL room temperature saline solution in opposite eyes. The solutions (warmed versus room temperature) and the order of irrigation (right eye versus left) were separately randomized. Physicians were blinded to solution temperature. Subjects rated the discomfort of irrigation on separate visual analog scales (VAS). The study had 80% power to detect at least a 12-mm difference in VAS readings. RESULTS: Thirty-five volunteers were enrolled in the study. There was no gender effect or order effect for the 2 solutions. The mean VAS score for warmed saline solution was 15 mm+/-15 mm (SD). The mean VAS score for room temperature saline was 34 mm+/-24 mm (SD), (95% confidence interval for difference of 19 mm [10 mm to 28 mm], P <.0001, Wilcoxon signed rank test). CONCLUSION: Warmed saline solution was both clinically and statistically more comfortable than room temperature saline solution as an ocular irrigant among normal volunteers.

Adult↗
PubMed1998

The physiological response to norepinephrine during hypothermia and rewarming.

Our purpose was to determine if core hypothermia influences physiological responses to norepinephrine (NE); and if rewarming reverses these effects. Animals were instrumented to measure mean arterial pressure (MAP) and cardiac output (CO). Core temperature was manipulated from 37.5 degrees C (normothermia), to 30 degrees C (hypothermia) and the back to 37.5 degrees C (rewarming) using an external arterial-venous femoral shunt. At each of these temperatures, baseline CO and MAP were measured. Norepinephrine (NE) was infused at rates to deliver 0.2, 1.0, or 5 microg kg(-1) per h. At each dose CO and MAP was measured again. Systemic vascular resistance (SVR) was calculated using the formula (SVR = (MAP/CO) x 80). Eight animals underwent all three phases of the protocol. The response to NE during normothermia was a significant increase in MAP to doses of 1 microg kg(-1) per min (P < 0.01) and 5 microg kg(-1) per min (P < 0.01) and SVR to doses of 1 microg kg(-1) per min (P < 0.01) and 5 microg kg(-1) per min (P < 0.01). The response to NE during hypothermia was a significant increase in MAP only at doses of 1 microg kg(-1) per min (P = 0.03) and 5 microg kg(-1) per min (P = 0.01). The response to NE after rewarming was a significant increase in MAP only at a dose of 5 microg kg(-1) per min (P = 0.03). This study shows that core hypothermia causes a change in physiological response to NE that rewarming does not reverse.

Adrenergic alpha-Agonists↗
PubMed1998

Neurophysiologic effects of retrograde cerebral perfusion used for aortic reconstruction.

OBJECTIVE: The results of neurophysiologic monitoring using somatosensory evoked potentials (SSEPs) and electroencephalography (EEG) were analyzed to determine if retrograde cerebral perfusion (RCP) supported central nervous system electrical function during surgery that required temporary interruption of antegrade cerebral perfusion (IACP). DESIGN: A prospective, observational study. SETTING: A university hospital. PARTICIPANTS: Fifteen adult patients who underwent aortic reconstruction using RCP and three patients who underwent thoracic aortic operations using hypothermic circulatory arrest without RCP. INTERVENTIONS: SSEPs and EEG were monitored continuously throughout the operation. Regression analysis was performed to determine the factors that affected the rate of decrease in SSEP amplitudes during IACP and the time required for SSEP and EEG activity to recover after antegrade cerebral perfusion (ACP) was restored. MEASUREMENTS AND MAIN RESULTS: The amplitude of SSEPs that were elicited decreased over time after IACP. The mean +/- standard deviation (SD) time required for the brachial plexus (Erb's point), cervicomedullary junction (N13), and brainstem (N18) SSEPs to decrease to 0.5 of their original amplitude after IACP were 30 +/- 2, 19 +/- 2, and 16 +/- 2 minutes, respectively. The rate of decrease in the N18 SSEP amplitude after IACP correlated positively to the fraction of no-flow time (p = 0.01). CONCLUSION: RCP attenuated the rate of decay in SSEP amplitudes during IACP. This suggested that RCP had a measurable physiologic effect on central nervous system function and may increase the time that ACP can be safely interrupted.

Adult↗
PubMed1998

Relationships between cerebral blood flow velocities and arterial pressures during intra-aortic counterpulsation.

OBJECTIVE: To determine the effects of intra-aortic counterpulsation (IABP) on cerebral blood flow velocity. DESIGN: Prospective self-controlled study. SETTING: University hospital surgical intensive care unit. PARTICIPANTS: Nineteen cardiac surgical patients requiring perioperative IABP assistance. INTERVENTIONS: Simultaneous recording of transcranial Doppler middle cerebral artery blood flow velocity and arterial pressure in response to changes in the magnitude of augmentation and trigger ratio. MEASUREMENTS AND MAIN RESULTS: Instantaneous cerebral blood flow velocities correlated with arterial pressures during IABP (r = 0.650) at different magnitudes of augmentation and trigger ratios. The increase in arterial pressure during balloon inflation was associated with an increase in cerebral blood flow velocity, and the decrease in arterial pressure in response to balloon deflation was associated with a decrease in cerebral blood flow velocity that was dependent on the magnitude of augmentation. Different magnitudes of augmentation or trigger ratios had no effect on peak systolic cerebral blood flow velocity, mean cerebral blood flow velocity, mean arterial pressure, or the mean velocity-to-pressure ratio. Instantaneous cerebral blood flow velocity to arterial pressure ratios were lowest in response to balloon deflation at the time of pre-ejection. CONCLUSIONS: IABP modified the phasic profile of cerebral blood flow to reflect the arterial pressure waveform without affecting mean cerebral blood flow velocity. Peak systolic cerebral blood flow velocity was maintained in augmented beats despite the decreased systolic arterial pressure associated with afterload reduction. The acute decrease in cerebral blood flow velocity at pre-ejection was balanced by increased cerebral blood flow velocity during balloon inflation in diastole.

Adult↗
PubMed1998

Preflight versus en route success and complications of rapid sequence intubation in an air medical service.

BACKGROUND: Maintenance of an airway in the air medically transported patient is of paramount importance. The purpose of this study is to compare preflight versus en route rapid sequence intubation (RSI)-assisted intubations and to determine the value of air medical use of RSI. METHODS: This study is a 31-month retrospective review of all patients intubated and transported by a large city air medical service. Subgroup analysis was based on whether patients were transported from a hospital or a scene and whether they were intubated preflight or en route. Information on age, Glasgow Coma Scale score, type of scene, ground time, and previous attempts at intubation was recorded. Complications included failures, multiple attempts at intubation, arrhythmias, and need for repeated paralytic agents. Comparisons were made using a confidence interval analysis. An alpha of 0.05 was considered significant; Bonferroni correction was used for multiple comparisons. RESULTS: Three hundred twenty-five patients were intubated and transported by Lifeflight during the study period. Two hundred eighty-eight patients were intubated using RSI (89%). The success rate was 97%. Preflight intubations were performed on 100 hospital calls and 86 scene calls. En route intubations were performed on 40 hospital cases and 62 scene calls. Patients who underwent preflight intubations were significantly younger than those who underwent en route intubations for both the hospital group (34 +/- 11 vs. 44 +/- 24 years, p < 0.05) and the scene group (27 +/- 13 vs. 32 +/- 16 years,p < 0.05). Otherwise, the demographic characteristics of the four groups were similar. Trauma accounted for 60 to 70% of hospital transfers and almost 95 to 100% of scene calls. Compared with preflight intubations, there was a significant decrease in ground time for hospital patients who were intubated en route (26 +/- 10 vs. 34 +/- 11 minutes, p < 0.05) and for scene patients who were intubated en route (11 +/- 8 vs. 18 +/- 9 minutes, p < 0.05). There were no significant differences between the groups for number of failures (9 of 288), arrhythmias (18 of 288), or necessity for repeated paralysis (8 of 288). Multiple intubation attempts were performed in more scene preflight patients (30 of 86, 35%) than scene en route patients (16 of 62, 26%), but this did not reach statistical significance. Even for patients having previous attempts at intubation, the success rate using RSI was 93% (62 of 67). CONCLUSION: Air medical intubations, both preflight and en route, for both scene calls and interhospital transports, can be done with a very high success rate. Rapid sequence intubation may improve the success rate. For scene calls, there was a significant decrease in ground time, and there was a trend toward fewer multiple intubation attempts when the patient was intubated en route instead of preflight.

Adolescent↗
PubMed1998

Domestic violence awareness and prevalence in a first-year medical school class.

OBJECTIVE: To determine knowledge about domestic violence (DV), the effectiveness of formal instruction about DV, and the prevalence of DV in a first-year medical school class. METHODS: A general-knowledge survey of DV was given before and approximately 1 month after 3 hours of instruction provided by emergency medicine and internal medicine faculty. A previously validated scale, the Index of Spouse Abuse (ISA), was offered to determine baseline levels, of DV within the group. Differences in first-year medical student knowledge of facts about DV and differences in responses by men vs women were determined before and after the instruction. RESULTS: In the pre-instruction series, 144 of 148 (97%) participated. After the instruction, 141 of the same 148 students participated (95%). The prevalence of DV against women was correctly identified by 45% of the students as "15-30%" prior to instruction, and 65% after instruction. The prevalence of DV against males was correctly identified as "0-15%" by 48% of the students prior to instruction, and 70% after instruction. Before instruction, 29% of the students knew that "DV rates are equal in different socioeconomic groups," vs 72% after instruction. Similarly, prior to instruction 58% of the students knew that the victim is not responsible for the abuse, and 84% knew this after instruction. Before instruction 14 (10%) of the students believed they were victims of DV in the past, representing 7% of the men and 13% of the women. Before instruction neither group believed they were present victims of DV. However, according to ISA scoring, 6% of the women were positive for violence in the past, and approximately 5% were positive for present violence. No men were positive for ISA-determined past or present violence. CONCLUSION: Improvement in awareness was demonstrated after 3 hours of instruction in a first-year medical school class. There was DV among female medical students in this first-year class and self-reporting was not reliable. These results support instruction on DV for medical students.

Adult↗
PubMed1997

Cost minimization analysis of various treatment options for surgical stage I endometrial carcinoma.

PURPOSE: This study compares the payors' cost of treatment for surgical Stage I endometrial carcinoma with results of published clinical studies to determine which treatment most efficiently uses available resources. METHODS AND MATERIALS: Six options for treatment of surgical Stage I endometrial carcinoma were selected for comparison. The treatment options were observation only, low-dose-rate brachytherapy (LDRB) (nonremote afterloading), LDRB and external beam radiation (EBRT), EBRT only, high-dose-rate brachytherapy (HDRB) only (three applications), and EBRT and HDRB (three applications). The literature was reviewed to obtain disease-free survival (DFS) rates corresponding to the treatment options chosen in surgical Stages IA, IB, and IC. Metaanalysis and sensitivity testing were performed on the collected clinical data. A typical midsized city in Medicare region IV was used as our representative payor cost basis. RESULTS: Thirteen retrospective articles contained sufficient clinical information for analysis. Comparison of DFS between the observation, LDRB, and EBRT treatment groups was made for Stage IA; LDRB and EBRT for Stage IB; and LDRB, EBRT, LDRB +/- EBRT, LDRB + EBRT, and HDRB + EBRT for Stage IC. Meta-analysis failed to reveal statistically significant DFS between the respective treatment options within Stages IA, IB, or IC. The RVUs for each treatment option were LDRB, 21.7; EBRT, 117.1; EBRT + LDRB, 130.7; HDRB, 155.5; and EBRT + HDRB, 264.4. The DRG payment for LDRB is $2714.92. The calculated payor's cost for each treatment option was: LDRB, $3466.62; EBRT, $4053.03; EBRT + LDRB, $7238.55; HDRB, $5381.19; and EBRT + HDRB, $9153.14. CONCLUSION: Our analysis reveals no statistically significant differences in DFS among the treatment options considered within each surgical stage. Observation appears to result in acceptable DFS with minimal cost in Stage IA. Low-dose-rate brachytherapy was the most cost-effective treatment in Stage IB, with no statistically significant difference in DFS between LDRB and EBRT. Although LDRB had inferior DFS compared to other treatment options in surgical Stage IC, this difference failed to reach statistical significance. Our analysis implies, excluding observation, that LDRB may be a more cost-efficient treatment than the other treatment options considered. Further studies stratifying for surgical stage and grade are needed to determine the optimal cost-effective treatment for this common malignancy.

Aged↗