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Biomedical subjects

Joseph E Parrillo

Publications and source records attributed to Joseph E Parrillo.

At least 37 records · Page 2Linked to original sources
PubMed2004

Bacterial DNA and RNA induce rat cardiac myocyte contraction depression in vitro.

Sepsis and septic shock, the systemic immunologic and pathophysiologic response to overwhelming infection, are associated with perturbation of a variety of metabolic cell pathways and with multiple organ failure (MOF) including cardiac depression. This depression has been attributed to the effect of several circulating and locally produced proinflammatory mediators. Recent data suggest that bacterial nucleic acids can produce profound systemic inflammatory responses characterized by circulatory shock in intact animals. In this study, bacterial DNA and RNA derived from pathogenic clinical S. aureus and E. coli isolates are shown to induce early concentration-dependent depression of maximum extent and peak velocity of contraction of electrically paced neonatal rat ventricular myocytes in culture. Significant but more modest depression was generated by a nonpathogenic E. coli isolate. Pretreatment with a DNase or RNase abrogated this effect. Further, synthetic, double-stranded RNA (dsRNA) also induced concentration-dependent depression of myocyte contraction, with the effect also being prevented by pretreatment with RNase. These data suggest that bacterial DNA and RNA may contribute to myocardial depression during bacterial sepsis and septic shock.

Animals↗
PubMed2004

Pulmonary artery occlusion pressure and central venous pressure fail to predict ventricular filling volume, cardiac performance, or the response to volume infusion in normal subjects.

OBJECTIVE: Pulmonary artery occlusion pressure and central venous pressure have been considered to be reliable measures of left and right ventricular preload in patients requiring invasive hemodynamic monitoring. Studies in recent years have questioned the correlation between these estimates of ventricular filling pressures and ventricular end-diastolic volumes/cardiac performance variables in specific patient groups, but clinicians have continued to consider the relationship valid in the broader context. The objective of this study was to assess the relationship between pressure estimates of ventricular preload (pulmonary artery occlusion pressure, central venous pressure) and end-diastolic ventricular volumes/cardiac performance in healthy volunteers. DESIGN: Prospective, nonrandomized, nonblinded interventional study. SETTING: Cardiac catheterization and echocardiography laboratories. SUBJECTS: Normal healthy volunteers (n = 12 group 1, n = 32 group 2). INTERVENTIONS: Pulmonary catheterization and radionuclide cineangiography (group 1) and volumetric echocardiography (group 2) during 3 L of normal saline infusion over 3 hrs. MEASUREMENTS AND MAIN RESULTS: In group 1, the initial pulmonary artery occlusion pressure and central venous pressure did not correlate significantly with initial end-diastolic ventricular volume indexes or cardiac performance (cardiac index and stroke volume index). Changes in pulmonary artery occlusion pressure and central venous pressure following saline infusion also did not correlate with changes in end-diastolic ventricular volume indexes or cardiac performance. In contrast, initial end-diastolic ventricular volume indexes and changes in these ventricular volume indexes in response to 3 L of normal saline loading correlated well with initial stroke volume index and changes in stroke volume index, respectively. The relationship between left ventricular end-diastolic volume index and stroke volume index was confirmed in group 2 subjects using mathematically independent techniques to measure these variables. In addition, initial central venous pressure, right ventricular end-diastolic volume index, pulmonary artery occlusion pressure, and left ventricular end-diastolic volume index failed to correlate significantly with changes in cardiac performance in response to saline infusion in group 1 subjects. CONCLUSIONS: Normal healthy volunteers demonstrate a lack of correlation between initial central venous pressure/pulmonary artery occlusion pressure and both end-diastolic ventricular volume indexes and stroke volume index. Similar results are found with respect to changes in these variables following volume infusion. In contrast, initial end-diastolic ventricular volume indexes and changes in end-diastolic ventricular volume indexes in response to saline loading correlate strongly with initial and postsaline loading changes in cardiac performance as measured by stroke volume index. These data suggest that the lack of correlation of these variables in specific patient groups described in other studies represents a more universal phenomenon that includes normal subjects. Neither central venous pressure nor pulmonary artery occlusion pressure appears to be a useful predictor of ventricular preload with respect to optimizing cardiac performance.

Adolescent↗
PubMed2004

Critical care medicine as a distinct product line with substantial financial profitability: the role of business planning.

OBJECTIVE: As academic health centers face increasing financial pressures, they have adopted a more businesslike approach to planning, particularly for discrete "product" or clinical service lines. Since critical care typically has been viewed as a service provided by a hospital, and not a product line, business plans have not historically been developed to expand and promote critical care. The major focus when examining the finances of critical care has been cost reduction, not business development. We hypothesized that a critical care business plan can be developed and analyzed like other more typical product lines and that such a critical care product line can be profitable for an institution. DESIGN: In-depth analysis of critical care including business planning for critical care services. SETTING: Regional academic health center in southern New Jersey. SUBJECTS: None. INTERVENTIONS: As part of an overall business planning process directed by the Board of Trustees, the critical care product line was identified by isolating revenue, expenses, and profitability associated with critical care patients. MEASUREMENTS AND MAIN RESULTS: We were able to identify the major sources ("value chain") of critical care patients: the emergency room, patients who are admitted for other problems but spend time in a critical care unit, and patients transferred to our intensive care units from other hospitals. The greatest opportunity to expand the product line comes from increasing the referrals from other hospitals. A methodology was developed to identify the revenue and expenses associated with critical care, based on the analysis of past experience. With this model, we were able to demonstrate a positive contribution margin of dollar 7 million per year related to patients transferred to the institution primarily for critical care services. This can be seen as the profit related to the product line segment of critical care. There was an additional positive contribution margin of dollar 5.8 million attributed to the critical care portion of the hospital stay of patients admitted primarily through other product lines or the emergency room. This can be seen as the profit related to the "hospital service" segment of critical care. This represented a total contribution margin of dollar 12.8 million, approximately 24% of the institution's entire contribution margin. This information was subsequently used to develop strategic plans to promote this product line. CONCLUSIONS: We were able to define the critical care product line, and we were able to demonstrate profitability through an analysis of revenue and expenses related to critical care services. Our experience suggests that the concept of critical care as a product line, in addition to a hospital service, may lead to a useful analysis of this new discipline. This plan provided a rational foundation for development of the operating and capital budgets for the health system.

Academic Medical Centers↗
PubMed2004

Vasopressor and inotropic support in septic shock: an evidence-based review.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for vasopressor and inotropic support in septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and to improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591. CONCLUSION: An arterial catheter should be placed as soon as possible in patients with septic shock. Vasopressors are indicated to maintain mean arterial pressure of <65 mm Hg, both during and following adequate fluid resuscitation. Norepinephrine or dopamine are the vasopressors of choice in the treatment of septic shock. Norepinephrine may be combined with dobutamine when cardiac output is being measured. Epinephrine, phenylephrine, and vasopressin are not recommended as first-line agents in the treatment of septic shock. Vasopressin may be considered for salvage therapy. Low-dose dopamine is not recommended for the purpose of renal protection. Dobutamine is recommended as the agent of choice to increase cardiac output but should not be used for the purpose of increasing cardiac output above physiologic levels.

Cardiotonic Agents↗
PubMed2004

Immediate and 1-year survival of out-of-hospital cardiac arrest victims in southern New Jersey: 1995-2000.

Most studies report the out-of-hospital cardiac arrest (OHCA) survival to hospital discharge. One-year survival and neurological outcomes in southern New Jersey in 1996-2000 were analyzed using a retrospective data review. There were 1,597 cases of OHCA. Initial survival ranged between 15% in 2000 and 19% in 1997. Survival to hospital discharge, taken as a percent of the initial survivors, decreased from 44% in 1997 to 22% in 2000. In relation to all OHCA victims, survival to discharge decreased from 7.2% to 2.4%, respectively. On discharge from the hospital 19-50% of people had the diagnosis of anoxic brain damage. In ventricular fibrillation, survival to discharge was 41%, 46.7%, 40.7%, 37.5%, and 17.4%, respectively, from 1996 to 2000. The response time increased from 6.6 to 8.1 minutes. Correlation coefficient between in-hospital survival and response time was -0.73. The percent of people discharged with neurological damage increased from 38% to 50%. Initial survival was 29.2% in shockable and 7.5% in nonshockable rhythm (P < 0.001). Survival to discharge was 11.3% versus 1.6%, and survival to 1 year was 9.6% versus 0.7%, respectively (P < 0.001 for all). Overall, the neurologically favorable 1-year survival rate was 2.3% of all OHCA victims. One-year survival of OHCA victims without neurological deficits is low. In southern New Jersey the survival rate did not improve over the 5-year study. Not only initial (prehospital) mortality, but also "delayed" (in-hospital mortality) increases with increase of response time.

Brain Damage, Chronic↗
PubMed2004

Experimental human endotoxemia is associated with depression of load-independent contractility indices: prevention by the lipid a analogue E5531.

OBJECTIVE: To evaluate the efficacy of a novel lipopolysaccharide (LPS) antagonist, E5531, in blocking LPS-induced cardiac responses including myocardial depression (as assessed by relatively load-independent echocardiographic indices of contractility) in a human model of experimental endotoxemia. DESIGN: Randomized, prospective, placebo-controlled, double-blind trial. SETTING: ICU procedure room. PARTICIPANTS: Thirty-two healthy, male volunteers. INTERVENTIONS: Administration of LPS (4 ng/kg) and either a placebo or one of four sequential doses of E5531 (100 microg, 250 microg, 500 microg, or 1,000 microg) followed by volumetric echocardiography before and during 4-L saline solution infusion (3 L over 3 h, followed by 1 L over 2 h). RESULTS: In addition to the generation of a hyperdynamic circulation throughout the study period, administration of LPS resulted in a biphasic contractility response. Ejection fraction (EF), rate-corrected mean velocity of circumferential fiber shortening (Vcfc), peak systolic BP (SBP)/end-systolic volume index (ESVI) ratio, and end-systolic pressure (Pes)/ESVI ratio increased at the 3-h post-LPS assessment, compared to a control group of subjects receiving only similar amounts of saline solution (minimum p < 0.001). End-systolic myocardial wall stress (sigmaes)/ESVI ratio, one of the most load independent of the contractility indices, was unchanged. At 5 h after endotoxin, EF, Vcfc, SBP/ESVI, Pes/ESVI, and sigmaes/ESVI were all decreased (minimum p < 0.01), indicating myocardial depression. When present, early (3 h after LPS), apparent enhancement of myocardial contractility and later (5 h after LPS) myocardial depression were substantially blunted by administration of E5531 (minimum p < 0.025), typically in a concentration-dependent manner. CONCLUSIONS: Endotoxin generates significant myocardial depression when measured using highly load-independent indices of cardiac contractility. E5531 is a potent inhibitor of the early hyperdynamic cardiovascular and later myocardial depression response seen in experimental human endotoxemia.

Adolescent↗
PubMed2003

Alternative therapeutic strategies for patients with severe end-stage coronary artery disease not amenable to conventional revascularization.

Although there have been remarkable advances in medical therapy, percutaneous coronary interventions, and coronary artery bypass graft surgery, complete revascularization remains a challenge given the more complex coronary artery disease prevalent in contemporary practice. The lack of donors for cardiac transplantation will fuel the search for effective alternative strategies for dealing with patients with severe ischemic heart disease not amenable to conventional revascularization techniques. Percutaneous laser revascularization clearly diminishes anginal symptoms; however, the blinded trials have provided conflicting results, with one study showing a definite decrease in angina and another suggesting that the placebo effect may play a major role in this modality. Similarly, surgical transmyocardial laser revascularization is limited by the lack of consistent improvement in objective measurements of ischemia and the potential confounding mechanisms of denervation and the placebo effect, and thus should be reserved for only the most highly selected patients. Although enhanced external counterpulsation is associated with an improvement in anginal symptoms and exercise tolerance, this modality is limited by its availability, tolerability, and rigid exclusion criteria. Of the alternative strategies available, therapeutic angiogenesis holds the most promise. However, the long-term results of ongoing randomized clinical trials require further scrutiny. Novel methods for vascular reconstruction are evolving techniques, but should be viewed currently as mainly experimental methods. The common goals of these new treatment options would be to reduce symptoms, decrease morbidity, and potentially improve mortality by reducing ischemia through favorably impacting myocardial oxygen supply and demand. The optimal management of patients with severe end-stage coronary artery disease not amenable to conventional revascularization techniques will continue to remain a challenge for the clinician and will be the main focus of basic cardiovascular research and clinical trials in the new millennium.

Angioplasty, Laser↗
PubMed2003

Comparison of echocardiography using tissue harmonics and contrast harmonics with radionuclide angiography for the assessment of left ventricular function.

BACKGROUND: Left ventricular ejection fraction (LVEF) is a significant predictor of morbidity and mortality; however, the optimal noninvasive modality for the quantitative determination of LVEF is not apparent. HYPOTHESIS: We verified the hypothesis that the various echocardiographic methods of assessing LVEF using the Method of Discs with contrast (Optison human albumin microspheres; Amersham Health, Princeton, NJ) and visual assessment of LVEF using tissue harmonics and contrast harmonics compare favorably with radionuclide angiography (RNA). METHODS: In a prospective analysis, 24 consecutive patients scheduled to undergo RNA had an echocardiogram using tissue harmonics and contrast harmonics on the same day. LVEF was assessed by RNA by an experienced, blinded reader using manual determination of the region of interest. LVEF was calculated using the Method of Discs (Simpson's Rule) by a blinded sonographer. LVEF was visually estimated by two blinded readers using echocardiography with tissue harmonics and contrast harmonics on separate occasions. RESULTS: By linear regression analysis, LVEF determination by echocardiography with contrast using the Method of Discs correlated well with RNA (r = .835, p < .0005). Using Bland-Altman analysis, the second echocardiogram reader had excellent agreement with RNA, whereas the first reader had a mean difference of 5.25% (CI 1.3-9.2; p = .012) with visual assessment using tissue harmonics and a mean difference of 4.67% (CI 0.4-8.8; p = .031) with visual assessment using contrast harmonics compared with RNA. Thus, a small difference in agreement between RNA and echocardiographic visual estimation was noted that appeared to be primarily reader dependent. CONCLUSIONS: LVEF determination with echocardiography with contrast using the Method of Discs correlated well with RNA and provided agreement across a range of cardiac functions. Visual echocardiographic assessment of LVEF with both tissue harmonics and contrast harmonics correlated well with RNA, but contrast harmonics did not appear to offer an advantage over tissue harmonics alone.

Adult↗
PubMed2002

Protein-free phospholipid emulsion treatment improved cardiopulmonary function and survival in porcine sepsis.

Lipoprotein phospholipid (PL) plays a major role in neutralization of endotoxin. This study tested the hypothesis that prophylactic administration of a PL-enriched emulsion (PRE), which augments PL content of serum lipoproteins and neutralizes endotoxin in vitro, would preserve cardiovascular function and improve survival in porcine septic peritonitis. A control group was compared with low-, mid-, and high-dose treatment groups that received PRE by primed continuous infusion for 48 h. A fibrin clot containing live Escherichia coli 0111.B4 was implanted intraperitoneally 30 min after the priming dose. Survival increased in a dose-dependent manner and was correlated with serum PL. Infused PL was associated with high-density lipoprotein in the low-dose group and all serum lipoproteins at higher doses. Treatment significantly lowered serum endotoxin and tumor necrosis factor (TNF)-alpha, preserved cardiac output and ejection fraction, and attenuated increases in systemic and pulmonary vascular resistances. This study demonstrated that augmentation of lipoprotein PL via administration of PRE improved survival and offered a novel therapeutic approach to sepsis.

Animals↗
PubMed2002

Clinical review: Myocardial depression in sepsis and septic shock.

Myocardial dysfunction frequently accompanies severe sepsis and septic shock. Whereas myocardial depression was previously considered a preterminal event, it is now clear that cardiac dysfunction as evidenced by biventricular dilatation and reduced ejection fraction is present in most patients with severe sepsis and septic shock. Myocardial depression exists despite a fluid resuscitation-dependent hyperdynamic state that typically persists in septic shock patients until death or recovery. Cardiac function usually recovers within 7-10 days in survivors. Myocardial dysfunction does not appear to be due to myocardial hypoperfusion but due to circulating depressant factors, including the cytokines tumor necrosis factor alpha and IL-1beta. At a cellular level, reduced myocardial contractility seems to be induced by both nitric oxide-dependent and nitric oxide-independent mechanisms. The present paper reviews both the clinical manifestations and the molecular/cellular mechanisms of sepsis-induced myocardial depression.

Cardiac Output, Low↗
PubMed2002

Adenosine deaminase inhibition attenuates microvascular dysfunction and improves survival in sepsis.

The ability of increased endogenous adenosine to mitigate microvascular derangements in sepsis was studied. Pentostatin (2'-deoxycoformycin), an inhibitor of adenosine deaminase, was administered to mice immediately after induction of sepsis by cecal ligation and puncture. Intravital video microscopy of cremasteric postcapillary venules was performed. Leukocyte rolling and adhesion were significantly increased in septic mice compared with control mice. Treatment of septic mice with pentostatin significantly decreased leukocyte rolling and adhesion (6.02 +/- 0.09 versus 1.72 +/- 0.12 rolling cells/min, 2.07 +/- 0.04 versus 0.62 +/- 0.05 adherent cells/100 microm per minute; p < 0.001). Albumin leakage (ratio) was significantly attenuated in septic animals treated with pentostatin (0.42 +/- 0.05 versus 0.21 +/- 0.04; p < 0.01). Circulating levels of interleukin-6, tumor necrosis factor-alpha, and soluble tumor necrosis factor type II receptor were decreased in septic mice treated with pentostatin. Survival was significantly improved at 48 hours in mice treated with pentostatin. These results suggest an important role for adenosine in modulating both leukocyte-dependent and -independent mechanisms of endothelial injury in sepsis. Exploiting the advantageous action of endogenous adenosine represents a potentially useful and novel therapeutic approach for the treatment of sepsis.

Adenosine Deaminase↗
PubMed2002

Frequency of abrupt vessel closure and side branch occlusion after percutaneous coronary intervention in a 6.5-year period (1994 to 2000) at a single medical center.

The aims of this study were to analyze the contemporary trends in the changing incidence of abrupt vessel closure (AVC) after percutaneous coronary intervention (PCI), to determine the impact of intracoronary stenting and glycoprotein IIb/IIIa inhibitors (GPIs) on complication rates and etiologies, and to determine the incidence of side branch occlusion (SBO) as the etiology of AVC in the stent era, complications occurring during 3,300 consecutive PCIs performed from April 1994 to December 2000 at a single referral institution. In this consecutive patient cohort of PCI cases collected over a 6.5-year period, AVC occurred in 103 of 3,300 cases (3.12%). Linear regression analysis over this time frame documented a steadily decreasing incidence of AVC from 5.9% in 1994 to 1.1% in 2000 (-0.76%/per year, 95% confidence interval -0.99 to 0.52, p <0.05). Analysis using Pearson's correlation showed that the decreasing incidence of AVC was inversely correlated with the increasing percentage of intracoronary stents placed over this time period (r = -0.94, p <0.001). Additionally, GPI use increased from 0% in 1995 to 36.0% in 2000 (p = 0.009). The absolute incidence of SBO of a major branch vessel remained relatively stable over this 6.5-year period. However, SBO appeared to be increasing as the etiology of AVC, and accounted for 9.0% of AVC in 1995 compared with 28.0% of AVC in 2000. This increasing trend of the percentage of SBO as the etiology of AVC appeared to correlate with the increased use of stents (r = 0.85, p = 0.015). Thus, the incidence of AVC steadily decreased over the 6.5-year time period, and was associated with the increased use of stents and GPIs; conversely, SBO accounted for an increasing percentage of AVC over this time period.

Academic Medical Centers↗
PubMed2002

Utility of history, physical examination, electrocardiogram, and chest radiograph for differentiating normal from decreased systolic function in patients with heart failure.

To determine whether clinical parameters alone can differentiate normal versus decreased systolic left ventricular function in patients with heart failure. Detailed clinical data were collected prospectively from 225 consecutive patients who were hospitalized with heart failure. Findings in patients with normal (ejection fraction > or =45%) or decreased (ejection fraction <45%) left ventricular function were compared. Systolic function was normal in 104 patients (46%) and decreased in 121 patients (54%). Patients with normal function were older (mean [+/- SD] age, 59 +/- 13 years vs. 54 +/- 13 years, P = 0.007) and more likely to be female (56% vs. 35%, P = 0.001), obese (body mass index > or =30 kg/m(2), 62% vs. 48%, P = 0.04), have marked systolic (> or =160 mm Hg, 50% vs. 27%, P <0.001) and diastolic (> or =110 mm Hg, 25% vs. 13%, P = 0.02) hypertension, and use calcium antagonists (34% vs. 14%, P = 0.001). Patients with decreased function were more likely to use alcohol (37% vs. 20%, P = 0.007), angiotensin-converting enzyme (ACE) inhibitors (85% vs. 62%, P <0.001), and digoxin (57% vs. 27%, P <0.001); and more likely to have tachycardia (51% vs. 32%, P = 0.004), rales (89% vs. 80%, P = 0.05), electrocardiographic left ventricular hypertrophy (42% vs. 22%, P = 0.002), left atrial abnormality (52% vs. 22%, P <0.001), or flow cephalization on chest radiograph (91% vs. 79%, P = 0.02). Only sex, tachycardia, and use of digoxin and ACE inhibitors were associated with ventricular function in multivariable analysis. However, the sensitivity, specificity, and predictive values for all clinical variables were low. Differences in clinical parameters in heart failure patients with decreased versus normal systolic function cannot predict systolic function in these patients, supporting recommendations that heart failure patients should undergo specialized testing to measure ventricular function.

Aged↗
PubMed2002

Cloning and characterization of the human heparanase-1 (HPR1) gene promoter: role of GA-binding protein and Sp1 in regulating HPR1 basal promoter activity.

Heparanase-1 (HPR1) is an endoglycosidase that specifically degrades the heparan sulfate chains of proteoglycan, a component of blood vessel walls and the extracellular matrix. Recent studies demonstrated that HPR1 expression is increased in a variety of malignancies and may play a critical role in tumor metastases. The HPR1 gene and its genomic structure have been recently cloned and characterized. To understand the mechanisms of HPR1 gene expression and regulation, we first mapped the transcription start site of the HPR1 gene and found that HPR1 mRNA was transcribed from the nucleotide position 101 bp upstream of the ATG codon. A 3.5-kb promoter region of the HPR1 gene was cloned. Sequence analysis revealed that the TATA-less, GC-rich promoter of the HPR1 gene belongs to the family of housekeeping genes. This 3.5-kb promoter region exhibited strong promoter activity in two thyroid tumor cell lines. Truncation analysis of the HPR1 promoter identified a minimal 0.3-kb region that had strong basal promoter activity. Truncation and mutational analysis of the HPR1 promoter revealed three Sp1 sites and four Ets-relevant elements (ERE) significantly contributing to basal HPR1 promoter activity. Binding to the Sp1 sites by Sp1 and to the ERE sites by GA-binding protein (GABP) was confirmed by electrophoretic mobility shift assay and competition and supershift electrophoretic mobility shift assays. Cotransfection of Sp- and GABP-deficient Drosophila SL-2 cells with the HPR1 promoter-driven luciferase construct plus the expression vector encoding the Sp1, Sp3, or GABP gene induced luciferase gene expression. Mutation or truncation of the Sp1 or ERE sites reduced luciferase expression in both SL-2 cells and thyroid tumor cell lines. Coexpression of GABPalpha/beta and Sp1 or Sp3 further increased luciferase reporter gene expression. Our results collectively suggest that Sp1 cooperates with GABP to regulate HPR1 promoter activity.

Base Sequence↗