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PubMed1994

Right ventricular dysfunction: an independent predictor of adverse outcome in patients with myocarditis.

To assess the predictive value of right ventricular systolic function in patients with active myocarditis, the echocardiograms of 23 patients with biopsy-confirmed myocarditis were reviewed. Right ventricular systolic function was evaluated qualitatively and quantitatively by descent of the right ventricular base. Patients were divided into those with normal right ventricular function, in whom right ventricular descent was 1.9 +/- 0.1 cm, and those with abnormal right ventricular function, in whom right ventricular descent was 0.8 +/- 0.1 cm (p < 0.001). There were no differences between the two groups in age, duration of symptoms, baseline hemodynamics, or histologic assessment. Initial left ventricular ejection fraction was significantly lower in patients with depressed right ventricular function (27.5 +/- 4.9%) compared with that in patients with normal right ventricular function (47.5 +/- 6.3%) (p = 0.01). The likelihood of an adverse outcome, defined as death or need for cardiac transplantation, was greater in patients with abnormal right ventricular function (right ventricular descent < or = 1.7 cm) than in patients with normal right ventricular function (right ventricular descent > 1.7 cm) (p < 0.03). Multivariate analysis revealed that right ventricular dysfunction as quantified by right ventricular descent was the most powerful predictor of adverse outcome.

Female↗

PubMed1990

Hospitalization decision in patients with community-acquired pneumonia: a prospective cohort study.

PURPOSE: To identify a low-risk subset of patients with community-acquired pneumonia that could safely be treated in the ambulatory setting; and to assess how clinicians make the hospitalization decision. PATIENTS AND METHODS: We performed a prospective, observational study of 280 ambulatory and hospitalized adults with clinical and radiographic evidence of pneumonia. Patients were followed to assess all potential morbid complications and 6-week mortality. Physicians responsible for managing these patients were surveyed to assess the reasons for treating in a hospital or ambulatory setting and the therapies that dictate hospitalization. RESULTS: Sixty-one percent (170 of 280) of patients did not have an indication for admission at presentation using modified Appropriateness Evaluation Protocol criteria (a severe vital sign abnormality, alteration in mental status, suppurative complication, arterial hypoxemia, severe laboratory abnormality, or an acute coexistent medical problem requiring admission independent of the pneumonia). Among these 170 patients, 38% had a complicated course defined as death within 6 weeks, development of a new suppurative or medical complication due to pneumonia, intensive care unit admission, persistent fever or use of intravenous fluids or oxygen beyond 3 days, hospitalization lasting more than 3 days, or subsequent hospitalization in patients initially treated in the ambulatory setting. Five predisposing factors for a complicated course were identified in logistic regression models. The odds ratio for age more than 65 years was 2.7; for comorbid illness, 3.2; for temperature more than 38.3 degrees C (101 degrees F), 4.1; for immunosuppression, 12.0; and for a high-risk etiology, 23.3. The risk of a complicated course increased linearly with the number of risk factors, from 12% with none to 100% with four or more factors (p less than 0.001). Physicians most often relied on the general clinical appearance of the patient when making the triage decision, and most commonly cited intravenous antibiotics and chest physical therapy as treatments requiring hospitalization. CONCLUSIONS: If validated, our findings could improve physicians' assessment of prognosis, and may identify a low-risk subset of patients with community-acquired pneumonia who could safely be managed in the ambulatory setting.

Adult↗

PubMed1994

Selenite induction of DNA strand breaks and apoptosis in mouse leukemic L1210 cells.

The effects of selenite on DNA integrity, cell viability, and long-term proliferative potential of mouse leukemic L1210 cells were examined in this study. Selenite treatment resulted in concentration-dependent increases in DNA single-strand breaks and double-strand breaks, as detected by a modified filter elution assay. A time-course experiment showed that DNA single-strand breaks preceded DNA double-strand breaks. Agarose gel electrophoresis of DNA extracted from selenite-treated cells displayed a nucleosomal fragmentation pattern that is characteristic of apoptotic cell death. The involvement of a Ca2+,Mg(2+)-dependent endonuclease responsible for DNA double-strand fragmentation was implied by the observation that two inhibitors of endonuclease activity, i.e. aurintricarboxylic acid and zinc, blocked selenite-induced DNA double-strand breaks. These inhibitors also prevented selenite-induced cell death as defined by loss of ability to exclude trypan blue dye. Selenite treatment severely impaired the colony-forming ability of cells capable of trypan blue exclusion. The induction of DNA strand breaks and commitment to apoptosis may explain the selenite-mediated growth inhibition and loss of long-term proliferative potential.

Animals↗

PubMed1992

A dose-dependent increase of Tau immunostaining is produced by glutamate toxicity in primary neuronal cultures.

Neuronal degeneration was produced in primary cultures by glutamate exposure and the modifications of Tau immunoreactivity were analysed in degenerating neurons. After 8-12 days of culture, glutamate was applied at different concentrations (50, 100, 200 and 500 mumol) in a Na(+)- and Mg(2+)-free solution containing calcium. Prior to and 12 hours after glutamate exposure cell death was defined by cell counting in each dish. After fixation, neurons were processed for immunocytochemistry using a Tau2 monoclonal antibody and a Tau polyclonal antibody (Sigma). Tau immunostaining was scored by a blind count of immunoreactive cells and a semi-quantitative evaluation. The results show that the number of labelled neurons and the magnitude of neuronal immunolabelling are both related to the glutamate concentration. Our findings indicate that glutamate induces a dose-dependent increase of Tau immunoreactivity directly related to its cellular action on neuronal cells.

Alzheimer Disease↗

PubMed1986

Protection from venous air embolism with fluorocarbon emulsion FC-43.

Intraoperative venous air embolism (VAE) occurs frequently in some surgical settings and may cause devastating hemodynamic consequences. Perfluorocarbon emulsions have been investigated as artificial oxygen carrying medias. They also have the properties of enhanced nitrogen solubility and a small particle size. FC-43 (Oxypherol, Alpha Therapeutic Corp., Los Angeles, California) was compared to three other volume expanders in 91 New Zealand White laboratory rabbits exposed to continuous VAE. The animals were anesthetized and ventilated by one of four modalities. They then received one of the volume expanders at 20 cc/kg over 30 min. After a 10-min stabilization period, a constant femoral venous air infusion (0.25 cc/kg/min) was begun and continued until death. Time until death, total volume of air infused, femoral arterial pressure, central venous pressure, and ECG (Lead II) were recorded. Death was defined as the cessation of pulsatile blood pressure. Arterial and central venous gases were analyzed pre and post volume expansion and at intervals of every 5 min after the beginning of the femoral air infusion. Results showed a significant prolongation of life for the animals receiving FC-43 at 10 and 20 cc/kg as a volume expander and mechanically ventilated with 100% oxygen as compared to all other groups (P less than 0.05). PaO2 and PvO2 were consistently higher in the group receiving FC-43 as a volume expander. Central venous pressure was lower during air embolism in the FC-43 group. The mechanism for the enhanced survivability of rabbits pretreated with FC-43 volume expansion exposed to VAE is under further investigation.

Animals↗

PubMedDate not supplied

The treatment of kala-azar in the Sudan with sodium stibogluconate: a randomized trial of three dosage regimens.

In a randomized study in the Sudan, 3 different regimens of sodium stibogluconate were compared in patients with parasitologically confirmed kala-azar (visceral leishmaniasis): 10 mg/kg for 30 d (38 patients), 20 mg/kg for 30 d (29 patients), and 20 mg/kg for 15 d (37 patients). Treatment failures were defined as death, partial response, relapse, or the development of post-kala-azar dermal leishmaniasis. The hazard ratio for failure of 20 mg/kg for 30 d vs. 10 mg/kg for 30 d 2.1 (95% confidence interval [CI] = 0.6, 7.6) and for 20 mg/kg for 15 d vs. 10 mg/kg for 30 d it was 1.7 (95% CI = 0.5, 6.1). No significant difference was detected between the 3 regimens in the rate of return to normal of haematological criteria, regression of spleen size, or weight gain. After 15 d treatment parasite clearance with 20 mg/kg for 30 d and 20 mg/kg for 15 d was more profound than with 10 mg/kg for 30 d (P < 0.05), but the difference was no longer present at the end of treatment. Further investigation of the effectiveness of short, intensive treatment regimens in the treatment of kala-azar is warranted.

Adolescent↗

PubMed1987

Cellular aging (the Hayflick limit) and species longevity: a unification model based on clonal succession.

A model is presented which proposes a specific cause-and-effect relationship between a limited cell division potential and the maximum lifespan of humans and other mammals. It is based on the clonal succession hypothesis of Kay which states that continually replicating cell beds (e.g. bone marrow, intestinal crypts, epidermis) could be composed of cells with short, well-defined division potentials. In this model, the cells of these beds are proposed to exist in an ordered hierarchy which establishes a specific sequence for cell divisions throughout the organism's lifespan. The depletion of division potential at all hierarchical levels leads to a loss of bed function and sets an intrinsic limit to species longevity. A specific hierarchy for cell proliferation is defined which allows the calculation of time to bed depletion and, ultimately, to organism mortality. The model allows the existence of a small number (n) of critical cell beds within the organism and defines organism death as the inability of any one of these beds to produce cells. The model is consistent with all major observations related to cellular and organismic aging. In particular, it links the PDLs (population doubling limit) observed for various species to their mean lifespan; it explains the slow decline in PDL as a function of age of the donor; it establishes a thermodynamically stable maximum lifespan for a disease-free population; and it can explain why tissue transplants outlive donors or hosts.

Aging↗

PubMed1992

Respiratory disease in very-low-birthweight infants after prenatal thyrotropin-releasing hormone and glucocorticoid. TRH Study Group.

Although prenatal glucocorticoid treatment reduces neonatal respiratory morbidity, respiratory distress syndrome and chronic lung disease (CLD) develop in many very-low-birthweight infants despite therapy. To investigate the effect of additional prenatal treatment with thyrotropin-releasing hormone (TRH), we did a multicentre, blinded, randomised trial. 404 women with threatened preterm delivery at less than 32 weeks' gestation received betamethasone plus TRH (4 doses of 400 micrograms 8-hourly) or betamethasone plus placebo. 103 infants who were fully treated and of less than 1500 g birthweight were evaluated during the neonatal period. TRH treatment (55 infants) did not affect the total incidence of respiratory distress syndrome (47% vs 58% in controls) or of severe respiratory distress syndrome (13% vs 25% in controls, p = 0.11). CLD (defined as requirement for supplemental oxygen at 28 days after birth) developed in significantly fewer TRH-treated infants (18% vs 44% of controls, p less than 0.01). The unadjusted relative risk of CLD with TRH therapy was 0.40 (95% CI 0.26-0.80, p less than 0.05), and this was not materially changed after adjustment for potentially modifying variables. There were significantly fewer adverse outcomes, defined as death or continuing oxygen requirement, in the TRH group than in the steroid-alone group both at 28 days and when infants reached 36 weeks' postconceptional age. The incidence of other complications of prematurity was similar in the two groups. Prenatal TRH reduces the incidence of chronic lung disease among betamethasone-treated infants.

Betamethasone↗

PubMed1985

Current status of bioassays in genetic toxicology--the dominant lethal assay. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

The term dominant lethal may be defined as death of the heterozygote arising through multiple chromosomal breaks. The assay is generally conducted by treating male animals, usually mice or rats, acutely (1 dose), subacutely (5 doses), or over the entire period of spermatogenesis. Animals treated acutely or subacutely are mated at weekly intervals to females for a sufficient number of weeks to cover the period of spermatogenesis. Those treated for the entire spermatogenic cycle are mated for 1 or 2 successive weeks at the termination of treatment. Females usually are killed at 14 days of pregnancy and examined for the number of total implantations in the uterus, the number of implantations classified as early deaths, and, in some cases, the number of corpora lutea. The category of early death is the most significant index of dominant lethality. A total of 249 papers were reviewed and 140 chemicals were evaluated. Of the 140 chemicals, 65 were positive by the criteria used by the Work Group in evaluating each publication. The category of "positive" includes those responses of a borderline nature. 99 chemicals were declared negative. There is considerable overlap of chemicals in both categories, which accounts for the incongruity in the total number of chemicals tested and the number considered positive and negative. A total of 44 animal carcinogens have been tested in the dominant lethal assay, 26 of which were positive and 18 negative for a correlation of 59%. The role of the assay should be that of confirming positive results from lower tier chromosomal aberration-detecting systems (confirming in the sense of indicating the ability of the chemical to penetrate gonadal tissue and to produce cytogenetic damage). The dominant lethal assay should not be used as a risk assessment method.

Animals↗

PubMed1990

Additional prognostic value of exercise testing and thallium-201 scintigraphy in catheterized patients without previous myocardial infarction.

To determine whether exercise testing and thallium scintigraphy provide additional prognostic information in symptomatic patients undergoing catheterization, we studied 432 consecutive male patients without a previous myocardial infarction by means of an exercise test, thallium scintigraphy and catheterization. The follow-up period was 46 +/- 24 months (from 12 to 96). Events were defined as death (27 patients), nonfatal myocardial infarction (occurring in 27 patients) or late (greater than 60 days after test) surgery or dilatation (needed in 45 patients). The 5 year survival rate was 89% and the event-free rate was 72%. History, noninvasive and invasive variables were submitted to a stepwise Cox regression analysis. By multivariate analysis, the significant variables related to death were the number of diseased vessels and exercise workload; the selected variables for all cardiac events were the number of diseased vessels; the score at thallium exercise testing and exercise workload. Among the subgroups of 337 coronary patients, the predictive variables for death were exercise workload and the number of diseased vessels. For all cardiac events, the selected variables were the number of diseased vessels, the score of defects during thallium exercise and exercise workload. Thus, in patients without a previous myocardial infarction, noninvasive variables do provide prognostic information which is not available either from the history or from catheterization.

Cardiac Catheterization↗

PubMed1994

The prognostic significance of urinary albumin in Polynesians with non-insulin-dependent diabetes.

Polynesian (59 Maori and 30 Pacific Island) patients were identified from two diabetes clinic registers and followed for a mean of 4.8 years, in order to determine the prognostic significance of urinary albumin excretion. Events were defined as death or entry onto a renal replacement programme. Fourteen events occurred during the period of follow-up. Urinary albumin/creatinine ratio was treated as a continuous variable in a proportional hazards analysis. A 10-fold increase in albumin/creatinine ratio was associated with a 5-fold increase in the risk of an event (95% C.I. = 2.05-12.09). In conclusion, elevated urinary albumin/creatinine predicted mortality and renal morbidity in Maori and Pacific Island patients with non-insulin-dependent diabetes.

Albuminuria↗

PubMed1994

A technique for using neural network analysis to perform survival analysis of censored data.

The purpose of this study was to demonstrate how a form of neural network analysis could be used to perform survival analysis on censored data, and to compare neural network analysis with the most commonly used technique for this type of analysis, Cox regression. In this study computer simulated data sets were used. The underlying rules connecting prognostic information to the hazard of death were defined to allow the construction of data sets with specific realistic properties that could be used to demonstrate situations in which neural network analysis had particular strengths in comparison with Cox regression modeling. Using these simulated data sets neural network analysis could produce successful predictive models, find interactions between variables, and recognize the importance of variables that contributed to the hazard rate as a complex function of the variables value and in situations where the proportionality of hazards assumption was violated. It was also demonstrated that neural network analysis was not a 'black box', but could lead to useful insights into the roles played by different prognostic variables in determining patient outcome.

Humans↗

PubMed1992

Intracoronary ultrasound predictors of adverse outcomes after coronary artery interventions.

OBJECTIVES: The purpose of this study was to determine the association between qualitative and quantitative lesion characteristics as assessed by intracoronary ultrasound imaging and adverse outcomes after coronary artery interventions. BACKGROUND: Restenosis and other adverse outcomes after coronary artery interventions may be difficult to predict from clinical or angiographic data. Intracoronary ultrasound imaging provides additional data that could prove useful. METHODS: Immediately after successful coronary artery interventions (angiographic residual stenosis < or = 50%), 69 patients underwent intracoronary ultrasound imaging. Images were assessed qualitatively for plaque composition and topography and for dissection. Quantitative data included measurement of minimal lumen diameter, lumen area, plaque area and percent area stenosis at the treatment and adjacent reference sites. Adverse outcome was defined as death, coronary bypass surgery, myocardial infarction or angiographic restenosis. RESULTS: Of the 69 patients, 1 died, 3 had bypass surgery and 1 had a myocardial infarction before planned 6-month repeat catheterization. Two patients were lost to follow-up study. Of the remaining 62 patients, 56 (90%) agreed to follow-up catheterization and 25 (45%) of the 56 had restenosis. Thus, 30 patients had an adverse outcome and 37 had no adverse event. The incidence of dissection detected by ultrasound imaging after an intervention was significantly greater in patients with than in those without a subsequent adverse event (63% vs. 35%, p < 0.05). The severity of dissection also appeared to be related to outcome (p < 0.05). Other qualitative and quantitative variables were not significantly different between the two patient groups. CONCLUSIONS: Dissection, as assessed by intracoronary ultrasound imaging after a coronary artery intervention, can identify patients at increased risk of subsequent adverse events. Additional studies are warranted to explore whether such imaging may allow modification of interventional procedures to improve outcome.

Angioplasty, Balloon, Coronary↗

PubMed1994

Risk stratification for long-term outcome after elective coronary angioplasty: a multivariate analysis of 5,000 patients.

OBJECTIVES: We attempted to develop a statistical model to facilitate risk stratification for long-term outcome after elective coronary angioplasty. BACKGROUND: Our understanding of factors related to long-term outcome after coronary angioplasty is limited. Adequate assessment of risk indexes could potentially lead to more appropriate use of percutaneous revascularization. METHODS: We studied 5,000 consecutive patients and assessed 19 clinical and anatomic variables as predictors of long-term event-free survival. Events were defined as death of any cause, myocardial infarction, bypass surgery or repeat percutaneous transluminal coronary angioplasty. Cox proportional hazards models were used to develop an equation for predicting event-free survival in a subset of 4,000 patients. The equation was validated with the remaining 1,000 patients. Variables that were significantly associated with an adverse outcome in the multivariate model included age > 60 years, extent of disease, Canadian Cardiovascular Society functional class, previous coronary angioplasty, male gender, history of diabetes mellitus, history of hypertension and history of congestive heart failure. RESULTS: The statistical model was used to develop a simplified scoring system, and the patients were assigned to three risk subgroups. Event-free survival curves for the three groups were significantly different (p = 0.0001). High risk patients had worse outcomes for each of the end points compared with low and moderate risk patients (p < 0.02). CONCLUSIONS: We demonstrated that clinical and anatomic variables can be used to risk-stratify long-term outcome after angioplasty, that a simplified scoring system can be used for risk stratification and that high risk patients have a low event-free survival.

Aged↗

PubMed2006

Impact of race and ethnicity on inhospital outcomes after percutaneous coronary intervention (report from the 2000-2001 New York State Angioplasty Registry).

BACKGROUND: Studies regarding the impact of race and ethnicity on outcomes after percutaneous coronary intervention (PCI) in the modern era are limited. METHODS: Using the 2000 and 2001 New York State PCI Databases, we compared baseline clinical, demographic, and angiographic characteristics and subsequent inhospital events among 76,928 patients of black, Hispanic, and white racial/ethnic backgrounds. We sought to determine the influence of race and ethnicity, if any, on post-PCI outcomes. RESULTS: Blacks and Hispanics were younger and more likely to be hypertensive, diabetic, obese, in congestive heart failure, and have chronic renal insufficiency. Whites were more likely to be men, have multivessel disease, and receive a stent. There was no significant difference in unadjusted post-PCI inhospital mortality (0.7% for all groups) or major adverse cardiac event (defined as death, emergent coronary bypass, or stroke) among all 3 racial groups. After correcting for clinical and demographic variables, race/ethnicity was not a significant predictor of death or major adverse cardiac event. CONCLUSION: Minority patients of black and Hispanic decent have a significantly higher incidence of traditional cardiovascular risk factors and present for angioplasty at a younger age compared with whites. However, there is no significant difference in outcomes after angioplasty among these racial/ethnic groups.

Black or African American↗

PubMed2005

The PRoject of Ex-vivo Vein graft ENgineering via Transfection IV (PREVENT IV) trial: study rationale, design, and baseline patient characteristics.

BACKGROUND: Coronary artery bypass graft (CABG) surgery with autologous vein graft (VG) conduit is one of the most frequently performed operations in the United States. Unfortunately, many VGs become occluded during long-term follow-up largely because of neointimal hyperplasia. A novel approach to preventing neointimal hyperplasia is with the double-stranded oligonucleotide edifoligide (Corgentech Inc, South San Francisco, Calif). Edifoligide inhibits E2F, a transcription factor that activates cell-cycle genes responsible for neointimal hyperplasia. METHODS: PREVENT IV is a phase-III, multicenter, randomized double-blind placebo-controlled trial of ex vivo treatment of autologous VGs with edifoligide in patients undergoing initial CABG surgery. The primary end point is VG failure, defined as death or > or =75% stenosis in a treated VG at 12- to 18-month angiographic follow-up. Secondary end points include major adverse cardiac events through at least 5 years and adverse events through 30 days. RESULTS: Enrollment of 3014 patients from 107 sites was completed on October 22, 2003. The baseline and procedural characteristics of the PREVENT IV population are generally well matched to a contemporary population of patients undergoing initial CABG from the Society of Thoracic Surgeons National Database. Angiographic follow-up is ongoing and scheduled to be completed in March 2005. CONCLUSIONS: The PREVENT IV data will establish whether VG pretreatment with an E2F transcription factor decoy, edifoligide, can improve graft patency and reduce the long-term morbidity and mortality of patients undergoing CABG surgery.

Aged↗

PubMed2006

Clinical and angiographic analysis with a cobalt alloy coronary stent (driver) in stable and unstable angina pectoris.

The Clinical and Angiographic analysis with a Cobalt Alloy Coronary Stent (Driver) (CLASS) study was a prospective, nonrandomized, multicenter study designed to assess the safety and efficacy of a cobalt-chromium alloy-based stent in patients with stable or unstable angina pectoris. A total of 203 lesions were treated in 202 enrolled patients. The percentage of major adverse cardiac event-free patients was 87.6% (177 of 202) at 6 months (primary safety end point; major adverse cardiac events were defined as death, myocardial infarction, emergency bypass surgery, or target lesion revascularization [percutaneous transluminal coronary angioplasty or coronary artery bypass grafting]). The angiographic success rate (primary efficacy end point) was 100%, and the procedural success rate was 98%. The binary in-stent restenosis rate at 6 months was 12.6%. Our results have demonstrated that the Driver cobalt-chromium alloy stent can be used with a low 6-month incidence of major adverse cardiac events, a low 6-month binary restenosis rate, and high angiographic and procedural success rates.

Aged↗

PubMed2006

Comparison of sirolimus versus paclitaxel eluting stents for treatment of coronary in-stent restenosis.

In patients with in-stent restenosis (ISR) inside bare metal stents, drug-eluting stents reduce the recurrence of restenosis compared with balloon angioplasty. However, few data are available about this therapeutic modality in the case of diffuse restenosis. The aim of this study was to evaluate the immediate and mid-term outcome of sirolimus- and paclitaxel-eluting stent implantation in diffuse ISR and determine the predictors of clinical and angiographic restenosis recurrence. A series of 161 consecutive patients with 194 diffuse ISR lesions (>10 mm) treated with drug-eluting stent implantation were evaluated. Major adverse cardiac events were defined as death, myocardial infarction, and the need for target lesion revascularization. During a mean follow-up of 8.2 +/- 3.4 months, the cumulative incidence of major adverse cardiac events was 19% in the SES group and 24% in the PES group (p = 0.56). Angiographic follow-up was performed in 80% of the lesions. The overall restenosis rate was 22% and was not significantly different between lesions treated with sirolimus-eluting (20%) or paclitaxel-eluting (25%, p = 0.55) stents. The incidence of restenosis was higher in diabetics (32%) than in nondiabetics (16%, odds ratio 2.5, 95% confidence interval 1.1 to 5.5, p = 0.02). By multivariate analysis, diabetes was confirmed to be the only independent predictor of recurrent restenosis (odds ratio 3.53, 95% confidence interval 1.39 to 9.02, p = 0.008). In conclusion, drug-eluting stent implantation for diffuse ISR is associated with acceptable clinical and angiographic results. The association of diffuse restenosis and diabetes mellitus is an unfavorable condition leading to a high risk of recurrence.

Coronary Angiography↗