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Biomedical subjects

J G Murphy

Publications and source records attributed to J G Murphy.

At least 37 records · Page 2Linked to original sources
PubMed1996

High concentrations of active plasminogen activator inhibitor-1 in porcine coronary artery thrombi.

Addition of exogenous plasminogen activator inhibitor-1 (PAI-1) to fibrin clots inhibits fibrinolysis in vivo. However, it is unknown whether the localized concentrations of active PAI-1 necessary to produce this antifibrinolytic effect can be recruited to acute arterial thrombi by endogenous mechanisms. We measured PAI-1 activity and antigen in porcine coronary artery thrombi that formed in response to acute vascular injury. Mean PAI-1 activity in thrombi (n = 5) was 36 +/- 5.1 micrograms/mL, which is > 2000 times its concentration in normal porcine plasma. The presence of markedly elevated concentrations of active PAI-1 in thrombi was confirmed by an immunoactivity assay and by demonstrating formation of sodium dodecyl sulfate-stable complexes after addition of 125I-urokinase to thrombus extracts. Comparative analysis of PAI-1 antigen by Western blotting and urokinase inhibition assay suggested that approximately one third of thrombus-associated PAI-1 was active. Histological examination of coronary thrombi revealed that they consisted predominantly of dense aggregates of platelets with interspersed islands of fibrin, which closely resemble the histological appearance of thrombi in patients with myocardial infarction and unstable angina pectoris. Washed porcine platelets prepared from peripheral blood contained sufficient PAI-1 antigen and activity to account for the concentrations observed in coronary artery thrombi. However, the specific activity of human platelet PAI-1 was lower than that of porcine platelet PAI-1 (2% versus 50% active, respectively), and human platelets inhibited in vitro fibrinolysis to a lesser extent than did porcine platelets. These results indicate that active PAI-1 accumulates in porcine coronary artery thrombi in concentrations markedly higher than those present in plasma and that PAI-1 may be an important determinant of the known resistance of platelet-rich thrombi to lysis by tissue-type plasminogen activator. These studies also underscore the importance of considering possible species differences in protein function when comparing animal models of thrombosis to acute coronary thrombosis in humans.

Animals↗
PubMed1995

New developments in infective endocarditis.

Endocarditis as seen today differs significantly from that outlined by Sir William Osler in his famous Gulstonian lectures in 1885. The median age of the patients has increased; the spectrum of predisposing cardiac lesions has changed; more cases are due to unusual organisms, including gram-negative bacteria and fungi; and more cases present acutely and the classic findings of late endocarditis are seldom seen. Endocarditis was untreatable and uniformly fatal in 1885. Although continued advances in medical and surgical therapy have significantly increased survival, the recent appearance of multiresistant organisms in some cases is reminiscent of the Osler era. Recent advances in the diagnosis and management of endocarditis include the identification of a specific Staphylococcus aureus receptor protein on endothelial cells, better imaging of the cardiac structures using transesophageal echocardiography, improvement in clinical diagnostic criteria and surgical techniques, and the use of outpatient oral antibiotics for penicillin-sensitive streptococcal endocarditis.

Adult↗
PubMed1995

Validation of TRISS and ASCOT using a non-MTOS trauma registry.

OBJECTIVES: To validate the Trauma and Injury Severity Score (TRISS) and A Severity Characterization of Trauma (ASCOT) models for patients with blunt injuries using an independent trauma registry, and to develop new TRISS and ASCOT models for types of patients with blunt injuries and examine their fit. DESIGN: Retrospective analysis of clinical data from the Institute for Trauma and Emergency Care (ITEC). MATERIALS AND METHODS: Statistical models were developed using TRISS and ASCOT variables applied to ITEC data for patients with blunt injuries. These models were compared to Major Trauma Outcome Study (MTOS) models with regard to the resulting coefficients and hospital quality assessments. Also, separate models were developed for different groups of blunt injuries, and these models were compared with one another and tested for adequacy of fit. MEASUREMENTS AND MAIN RESULTS: ASCOT performed acceptably well when new coefficients were derived using ITEC data, but TRISS did not. Although the models developed from MTOS and from ITEC coefficients generally yielded similar hospital quality assessments, there were some notable exceptions. Some TRISS and ASCOT variables were not significantly related to survival for some subgroups of blunt injuries, and neither the TRISS nor the ASCOT model was an adequate predictor of survival for patients suffering from low falls. CONCLUSIONS: New TRISS and ASCOT coefficients should be derived if survival for patients with blunt injuries is to be predicted accurately in independent trauma registries. Also, it may be wise to consider developing separate models for subgroups of patients, particularly if hospitals in the registry have different mixes of patient types.

Hospitals↗
PubMed1995

Multivariate models for predicting survival of patients with trauma from low falls: the impact of gender and pre-existing conditions.

OBJECTIVE: To determine if pre-existing conditions significantly improve the ability of current (TRISS and ASCOT) methods for predicting survival of patients with trauma from low falls. DESIGN: Retrospective analysis using logistic regression models to identify significant independent predictors of survival. SETTING: Eight hospitals affiliated with New York Medical College. PATIENTS: A total of 1906 patients with trauma from low falls who were admitted to the eight hospitals between July 1987 and June 1989. MAIN RESULTS: Gender and several pre-existing conditions significantly improved the ability of age and the physiologic and anatomic variables contained in the TRISS and ASCOT methodologies to predict survival for trauma patients suffering from low falls, with males experiencing a lower probability of survival. Odds of survival for patients with these pre-existing conditions ranged from 0.18 to 0.59 times the odds of survival for similar patients without the pre-existing conditions when the TRISS variables were used, and from 0.23 to 0.56 times the odds for similar patients when ASCOT variables were used. Furthermore, some substantial differences were found when hospital performance was assessed with and without the benefit of pre-existing conditions. CONCLUSIONS: Pre-existing conditions and male gender are significantly related to survival of patients with trauma from low falls, and should be included along with age and the various physiologic and anatomic measures currently being used to predict survival for those patients.

Accidental Falls↗
PubMed1994

Endothelialization of cardiac valve bioprostheses.

The main disadvantage of implanted xenograft valves used in cardiac surgery is their poor clinical long-term result, due to early tissue degeneration. In order to improve the performance of such glutaraldehyde fixed bioprostheses, a biological coating with viable endothelial cells was suggested. Therefore, glutaraldehyde preserved bovine pericard patches, as well as commercially available xenograft valves, were lined using human venous endothelial cells or microvascular cells from the subcutaneous fat tissue. Before cells were transplanted into their new environment, grafts were treated with an amino acid solution in order to neutralize the cytotoxic effect of free aldehydes, and precoated with fibronectin-heparin and basic fibroblast growth factor (bFGF) or endothelial cell growth supplement (ECGS) in order to enhance cell proliferation. Coated specimens were kept in culture conditions for a further seven days. Proliferation of transplanted cells was verified by an increase of activation following 3H-thymidine incorporation, while the maintained metabolic cell activity was demonstrated via Prostacycline (PGI2) measurement. Morphology was evaluated by means of scanning electron microscopy (SEM). As evaluated by the beta-Counter, 7 ng/ml bFGF (288,727 +/- 39,668 counts on day 4) substantially enhanced cell proliferation after seeding, opposed to the stimulation with 30,000 ng/ml ECGS (91,924 +/- 1129 counts on day 4), (p < 0.001). The PGI2 release of transplanted cells was stimulated with 25 microM Na arachidonic acid by the factor 2.6 +/- 0.3 and inhibited with 5 mM acetylsalicylic acid by the factor 0.7 +/- 0.2 on day 4 when compared with the basic level.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Long-term outcome in patients undergoing surgical repair of tetralogy of Fallot.

BACKGROUND: Although corrective surgery for tetralogy of Fallot has been available for more than 30 years, the occurrence of late sudden death in patients in whom surgery was apparently successful remains worrisome. METHODS: We studied long-term survival among 163 patients who survived 30 days after complete repair of tetralogy of Fallot, examining follow-up hospital records and death certificates when relevant. RESULTS: The overall 32-year actuarial survival rate among all patients who survived surgery was 86 percent, as compared with an expected rate of 96 percent in a control population matched for age and sex (P < 0.01). Thirty-year actuarial survival rates were calculated for the patient subgroups. The survival rates among patients less than 5 years old, 5 to 7 years old, and 8 to 11 years old were 90, 93, and 91 percent, respectively--slightly less than the expected rates (P < 0.001, P = 0.06, and P = 0.02). Among patients 12 years old or older at the time of surgery, the survival rate was 76 percent, as compared with an expected rate of 93 percent (P < 0.001). The performance of a palliative Blalock-Taussig shunt procedure before repair, unlike the performance of a Waterston or Potts shunt procedure, was not associated with reduced long-term survival, nor was the need for a trans-annular patch at the time of surgery. Independent predictors of long-term survival were older age at operation (P = 0.02) and a higher ratio of right ventricular to left ventricular systolic pressure after surgery (P = 0.008). Late sudden death from cardiac causes occurred in 10 patients during the 32-year period. CONCLUSIONS: Among patients with surgically repaired tetralogy of Fallot, the rate of long-term survival after the postoperative period is excellent but remains lower than that in the general population. The risk of late sudden death is small.

Analysis of Variance↗
PubMed1993

Blood transfusion increases the risk of infection after trauma.

To determine whether blood transfusion influences infection after trauma, we analyzed data on 5366 consecutive patients hospitalized for more than 2 days at eight hospitals over a 2-year period. The incidence of infection was significantly related to the mechanism of injury: penetrating injuries, 8.9%; blunt injuries, 12.9%; and low falls, 21.4%. Stepwise logistic regression analyses of infection using the variables age, sex, respiration rate in the emergency department, Glasgow Coma Scale in the emergency department, Injury Severity Score, shock (systolic blood pressure < 90 mm Hg on admission to the emergency department), and log of total amount of blood transfused during hospitalization showed that amount of blood received and Injury Severity Score were the only two variables that were significant predictors of infection across groups. Even when patients were stratified by Injury Severity Score, the infection rate increased significantly with increases in numbers of units of blood. Blood transfusion in the injured patients is an important independent statistical predictor of infection. Its contribution cannot be attributed to age, sex, or the underlying mechanism of severity of injury.

Abbreviated Injury Scale↗
PubMed1993

A study of pneumatic antishock garments in severely hypotensive trauma patients.

The effectiveness of a pneumatic antishock garment (PASG) on severely hypotensive trauma patients (BP < or = 50 mm Hg) was studied using two data sets. The first included data from eight hospitals collected over 4 1/2 years; the second included 2 years of data from an additional eight hospitals. Data were collected by trained nurse abstractors whose interrater reliability was extremely high for AIS and ISS scoring. One hundred forty-two patients had blood pressures < 50 mm Hg. The PASG patients had a higher survival rate than non-PASG patients (Pr = 0.055). The PASG appeared to have the most effect on patients with abdominal injuries since no patient with such an injury survived unless a PASG was applied. Controlling for severity using the TRISS method, z scores indicated that the survival rate in the PASG group was significantly higher than expected whereas that in the non-PASG group was similar to that predicted; the same pattern was found when blunt injury and penetrating injury patients were analyzed separately. Improvement in survival among PASG patients occurred despite an average scene time that was 4.7 minutes longer than that for non-PASG patients. No improvement in survival among PASG versus non-PASG patients with blood pressures of 50-70 mm Hg or in those with blood pressures of 90 mm Hg or less was found. We conclude that the use of PASG in severely hypotensive patients (BP < or = 50) should be considered medically acceptable pending randomized controlled studies.

Abdominal Injuries↗
PubMed1993

Is 24-hour operating room staff absolutely necessary for level II trauma center designation?

Recent papers from established trauma centers reported average elapsed times from emergency department (ED) admission to the operating room (OR) of greater than 100 minutes for patients judged to be in immediate need of surgery. This study was undertaken to determine whether patients treated at an institution desiring level II trauma center designation in a geographic area with a low incidence of penetrating trauma suffered any adverse effects because of lack of a 24-hour in-house OR staff. Trauma registry data at The Stamford Hospital, a suburban community teaching hospital without OR nursing staff in-house at night, were reviewed and compared with data from three affiliated level I trauma centers and with established national standards using TRISS methodology. Of 659 major trauma patients, 86 (44 blunt, 42 penetrating) underwent surgery within 12 hours of admission. Patients' injuries were similar in severity to those seen at the affiliated trauma centers and to the Major Trauma Outcome Study population. Mortality rates were also similar. No statistically significant differences were seen in elapsed times from ED arrival to OR arrival even in the subgroup of patients with systolic blood pressure values of < or = 90 mm Hg. No unexpected adverse outcomes could be ascribed to the lack of 24-hour OR staffing in this setting. The estimated cost of providing additional OR staffing is $145,000 per year. Since times to the OR and outcomes were similar to those at level I centers, this expense may not be warranted.

Adolescent↗
PubMed1993

Dual response runs in prehospital trauma care.

The effects of dual responses [Basic Life Support (BLS) and Advanced Life Support (ALS)] on the outcomes of trauma patients were evaluated. Outcomes included changes in physiologic measurements between the scene and the emergency department (ED), and survival to hospital discharge. Data for 2394 patients with penetrating, motor vehicle crash (MVC), or other blunt injuries were included. Changes in physiologic measurements (Revised Trauma Scores) between the prehospital and ED settings were positively associated with documented ALS or dual response care. Survival to hospital discharge among penetrating injury patients was negatively related to dual responses, whereas that among MVC patients was positively associated with dual responses. Parallel results were found for a subset of more severely injured patients. Future research should confirm and refine these results so that protocols for the appropriate use of dual response runs can be developed.

Adult↗
PubMed1993

Basic life support versus advanced life support for injured patients with an injury severity score of 10 or more.

To study the value of advanced life support (ALS) compared with basic life support (BLS) for penetrating and motor vehicle crash (MVC) patients, data were collected from eight hospitals over 24 months on 781 consecutive patients with Injury Severity Scores > or = 10 as well as on a subset of 219 hypotensive patients. Initial prehospital Revised Trauma Scores (RTSs) were compared with initial emergency department RTSs. Scene times, total prehospital times, and the use of a pneumatic antishock garment (PASG), intravenous fluids, and endotracheal intubation were also documented. A modified TRISS method was used to compare mortality rates. The MVC ALS patients showed improvement in mean RTSs between prehospital and the emergency department while MVC BLS patients did not. Mean changes in blood pressure (BP) and the percentage of patients with improved BP were significantly higher among patients who received ALS; ALS was associated with increased use of PASGs and IV fluids. There were no differences between groups with respect to observed versus predicted mortality. Similar results were found in the hypotensive subset of patients. No benefit from the use of ALS for trauma patients with total prehospital times of less than 35 minutes was documented.

Accidents, Traffic↗
PubMed1992

Restenosis and the proportional neointimal response to coronary artery injury: results in a porcine model.

Restenosis is a reparative response to arterial injury occurring with percutaneous coronary revascularization. However, the quantitative characteristics of the relation between vessel injury and the magnitude of restenotic response remain unknown. This study was thus performed to determine the relation between severity of vessel wall injury and the thickness of resulting neointimal proliferation in a porcine model of coronary restenosis. Twenty-six porcine coronary artery segments in 24 pigs were subjected to deep arterial injury with use of overexpanded, percutaneously delivered tantalum wire coils. The vessels were studied microscopically 4 weeks after coil implantation to measure the relation between the extent of injury and the resulting neointimal thickness. For each wire site, a histopathologic score proportional to injury depth and the neointimal thicknesses at that site were determined. Mean injury scores were compared with both mean neointimal thickness and planimetry-derived area percent lumen stenosis. The severity of vessel injury strongly correlated with neointimal thickness and percent diameter stenosis (p less than 0.001). Neointimal proliferation resulting from a given wire was related to injury severity in adjacent wires, suggesting an interaction among effects at injured sites. If the results in this model apply to human coronary arteries, restenosis may depend on the degree of vessel injury sustained during angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1992

Comparison between TRISS and ASCOT methods in controlling for injury severity.

ASCOT was developed by Champion et al. to address known limitations to TRISS. The present research attempted to validate ASCOT using an independent trauma registry. Data were collected by the Institute for Trauma and Emergency Care (ITEC), New York Medical College, between July 1, 1987 and June 30, 1989; 5685 trauma patients admitted to three level I trauma centers or five non-trauma center hospitals were included. Information was gathered by trained nurse-abstractors using all available prehospital and hospital records. ASCOT and TRISS were compared using sensitivity, disparity, misclassification rates, and the Hosmer-Lemeshow goodness-of-fit statistics. Disparity and sensitivity rates were relatively low for both indexes, particularly among blunt injury patients. Total numbers of patients misclassified by TRISS and by ASCOT were similar; most misclassifications were made by both TRISS and ASCOT and involved nonsurvivors. Each method had advantages in predicting the outcomes of particular subgroups of patients; ASCOT with regard to predicting outcomes among patients with head injuries and in correctly classifying blunt injured patients; TRISS in correctly classifying survivors. We conclude (1) the relatively small gain in predictive accuracy by ASCOT over TRISS is largely offset by its complexity and increased computer processing requirements; (2) Hosmer-Lemeshow tests indicate that neither index provides good statistical agreement between predicted and actual outcomes among either blunt or penetrating injury patients. Future models should include additional variables, stratify patients by several injury causes, and use decision rules to select variables and variable weights.

Adult↗
PubMed1992

Percutaneous polymeric stents in porcine coronary arteries. Initial experience with polyethylene terephthalate stents.

BACKGROUND: To test the feasibility of percutaneous deployment of intracoronary polymeric stents, a prototype polyethylene terephthalate (PET) stent and a catheter-based delivery system were developed. METHODS AND RESULTS: Polymeric stents were deployed in the coronary arteries of 11 Yucatan swine: six stents were placed in the left anterior descending coronary artery, four stents were placed in the circumflex artery, and one stent was placed in the right coronary artery. Stent deployment was achieved by withdrawal of an outer delivery sheath, thus allowing the PET stent to self-expand to a preformed configuration. Two animals died during surgery, one during stent placement and the other several hours after implantation due to intracoronary thrombus formation. Two animals were electively sacrificed within 24 hours of stent implant to examine the adequacy of stent deployment within the coronary vessel. The remaining seven animals survived until the termination of the study 4-6 weeks later. Light microscopic examination of the stented vessels showed an extensive neointimal proliferative response with vessel occlusion in all animals who survived initial stent placement. There were two distinct types of histological responses to the PET stent--a chronic foreign body inflammatory response around the stent tines and a neointimal proliferative response in the center of the occluded vessel lumen. The histological response seen in the central area of the vessel was morphologically similar to that seen in patients with restenosis after successful percutaneous transluminal coronary angioplasty, whereas the morphological response seen at the periphery of the stent tine was similar to that exhibited by a chronic foreign body reaction and was not typical of that seen in a restenosis lesion. A ventricular aneurysm also developed in the area of myocardium that was previously supplied by the occluded vessel. CONCLUSIONS: This study demonstrates that percutaneous deployment of polymeric stents in the coronary arteries is technically feasible. The use of PET polymer was associated with an intense proliferative neointimal response that resulted in complete vessel occlusion. Histological examination of the stented segments of the vessel revealed no evidence that dissection of the vessel wall had occurred at the time of initial stent deployment. Although the PET polymer was of similar quality to that used in the manufacture of balloon angioplasty catheters, a toxic chemical or contaminant effect cannot be completely excluded as the stimulus to intimal proliferation. This finding may have relevance to the selection of materials for use as intravascular devices.

Animals↗
PubMed1991

Emboli in infective endocarditis: the prognostic value of echocardiography.

OBJECTIVE: To determine whether vegetations visualized on two-dimensional echocardiography are an independent risk factor for the development of subsequent emboli in patients with infective endocarditis and to assess the timing of emboli relative to the initiation of antimicrobial therapy. DESIGN: Investigator-blinded, retrospective incidence cohort study. SETTING: Tertiary referral center. PATIENTS: Patients with left-sided native valve infective endocarditis who had two-dimensional echocardiography within 72 hours of beginning antimicrobial therapy. MEASUREMENTS AND MAIN RESULTS: The crude incidence rate of first embolic events in patients receiving antimicrobial therapy was 6.2 per 1000 patient-days (95% CI, 4.2 to 9.2). The rates in patients with and without vegetations were 7.1 and 4.9 per 1000 patient-days, respectively (incidence rate ratio, 1.4; 95% CI, 0.6 to 3.3). The relation between vegetations and risk for emboli was microorganism-dependent: Stratified incidence rate ratios were 6.9 (95% CI, 1.1 to 42.5; P less than 0.05) and 1.0 (95% CI, 0.2 to 3.9) for viridans streptococcal and Staphylococcus aureus endocarditis, respectively. The rate of first embolic events diminished over time (P less than 0.001), falling from 13 per 1000 patient-days during the first week of therapy to less than 1.2 per 1000 patient-days after completion of the second week of therapy. CONCLUSIONS: Overall, the presence of vegetations on echocardiography was not associated with a significantly higher risk for embolus in patients with left-sided native valve infective endocarditis. The relative risk for embolic events associated with echocardiographically visualized vegetations may be microorganism-dependent, with a significantly increased risk seen only in patients with viridans streptococcal infection. The rate of embolic events declines with time after initiation of antimicrobial treatment.

Adolescent↗
PubMed1991

A comparison of diagnostic related group length of stay outliers: motor vehicle crash versus penetrating injuries.

The incidence and degree to which patients injured by motor vehicle crashes (MVCs) and penetrating wounds remain in the hospital beyond the diagnostic related group (DRG) mean length of stay (LOS) are compared. During a 12-month period, records for consecutive patients admitted to eight hospitals (including three trauma centers) were studied. Patients aged 13 or younger, staying less than 48 hours, or with major burns or only distal fractures were excluded. In that time, 2,914 patients were eligible. Twenty percent of injuries were penetrating; 27% were MVC injuries; and, 53% were blunt injuries from other causes. Patients injured in MVCs and with penetrating injuries were compared with respect to mean LOS, incidence of DRG outliers, number of hospital days beyond the DRG mean LOS, and demographic variables. Patients injured in MVCs had a greater proportion of DRG LOS outliers and higher mean numbers of DRG excess days than did patients with penetrating wounds (p less than 0.01, for both). Injuries were distributed among relatively more DRGs for MVC patients. The DRG scheme may lack sufficient attention to factors more likely to affect MVC patients, such as multiplicity of injuries, incidence of CNS injuries, ICU requirements, and older age. In structuring more appropriate reimbursement for trauma care, special attention must be paid to patients injured in MVCs.

Accidents, Traffic↗