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PubMed2002

Age-related determinants of outcome after acute myocardial infarction: a dobutamine-atropine stress echocardiographic study.

OBJECTIVES: To investigate the cause of worse survival in older patients after myocardial infarction (MI). DESIGN: Prospective 18-month and longer follow-up study of a cohort of 167 patients (mean age +/- standard deviation 58 +/- 12, including 71 aged >or=65) with acute MI for cardiac events, defined as cardiac death, recurrent MI, or resuscitated ventricular tachycardia or fibrillation (VT/VF). SETTING: Milwaukee County Medical Complex and the Zablocki Veterans Affairs Medical Center, Milwaukee, WI. PARTICIPANTS: One hundred sixty-seven patients who underwent dobutamine-atropine stress echocardiography (DASE) in the first week (2-7 days) after acute MI and were medically managed. MEASUREMENTS: Comparison of event rates in older (>or=65 years) and younger (<65 years) patients and of clinical, resting echocardiographic, DASE, and angiographic findings in patients with and without events. Coronary angiography was performed in 141. RESULTS: Older and younger patients tolerated DASE well. During follow-up, there were 29 cardiac events (cardiac death in 17, nonfatal MI in 10, and VT/VF in 2). Events were more common in older patients (26% vs 12%, P <.05), especially death (19% vs 5%, P <.05). Scar size in the infarct zone by DASE was larger (4.0 +/- 2.8 vs 3.0 +/- 2.7 segments, P <.05) and remote wall motion abnormalities more common (47 vs 29%, P <.05) in older patients. Univariate determinants of outcome (P <.05) in older patients were diabetes mellitus; remote wall motion abnormalities; angiographic multivessel disease; scar size; ejection fraction; and resting, low-, and peak-dose wall motion score. Univariate determinants in younger patients were similar, but diabetes mellitus was not. Multivariate analysis revealed that remote wall motion abnormalities and scar size by DASE were independently predictive of outcome in older and younger patients and diabetes mellitus only in older patients. Low- and peak-dose DASE data enhanced (P <.01) the prediction of outcome in all patients with acute MI relative to clinical data and resting echocardiography. CONCLUSION: DASE was more predictive of outcome than clinical data and resting echocardiography in both age groups. Scar size and remote wall motion abnormalities were the primary determinants of outcome irrespective of age. The worse prognosis of older patients correlated with diabetes mellitus, greater scar size, and higher incidence of remote inducible ischemia.

Age Factors↗

PubMed2002

Field triage of trauma patients: improving on the Prehospital Index.

The purpose of the present study was to evaluate the predictive ability of the Prehospital Index (PHI) in identifying injury severity and to develop a trauma triage scale that incorporates, along with the PHI, a subset of time independent variables to improve the predictive ability of the PHI-based triage instrument. This study included 1,291 trauma patients treated in Montreal, Canada. The developed trauma triage protocol was based on logistic regression analysis, in which the model that predicts the data best was selected by using Bayesian information criterion. The selected regression model included the variables age, body region injured, mechanism of injury, comorbidity, and PHI. This algorithm was a substantial improvement in detecting major versus non-major injuries (major injury defined based on death, intensive care unit admission, and surgery intervention) over the PHI alone (area under the receiver operating characteristic curve: 0.76 v 0.66, P <.05). Considering time independent variables could lead to better injury triage decisions.

Adolescent↗

PubMed2005

Morbidity and mortality are not increased after induction chemoradiotherapy followed by esophagectomy in patients with esophageal cancer.

Attempts to improve survival of patients with esophageal cancer have been made using induction chemoradiotherapy (CRT) followed by surgery. This approach may be associated with higher complication rates. A large single-center experience was reviewed to determine whether induction CRT was associated with increased morbidity and mortality among 179 patients undergoing esophagectomy between January 1994 and December 2002. Morbidity was recorded as any complication requiring additional intervention. Mortality was defined as patient death within the first 30 postoperative days or death during the initial hospitalization. In total, 131 patients underwent induction CRT followed by surgery. The most common operation was an Ivor-Lewis esophagogastrectomy (60%). Median survival of the entire group was 33 months and 5-year survival was 26%. Perioperative mortality was 5% and did not differ between induction (4.6%) and non-induction (6.3%) groups. The overall complication rate was 57%, reflecting a very liberal definition of postoperative complications. There were no differences between the two groups in terms of such major complications as anastomotic leak, pneumonia, acute respiratory distress syndrome, respiratory failure, chylothorax, atrial arrhythmia, and wound infections. There were only two complications that occurred more frequently in the induction group--venous thrombosis (8.4% v 0%) and vocal cord paresis (7.6% v 2.1%). The median hospital stay was similar in patients who had complications versus those who did not (12 v 13 days) and in patients who underwent induction CRT versus those that did not (12 days v 13.5 days). Esophagectomy can be performed safely with low mortality and acceptable morbidity following neoadjuvant chemotherapy and radiation with no increase in hospital stay for patients with complications.

Adenocarcinoma↗

PubMed1996

Adjustment of birth weight standards for maternal and infant characteristics improves the prediction of outcome in the small-for-gestational-age infant.

OBJECTIVE: Birth weight is a function of gestational age. Various maternal and infant characteristics also affect birth weight. This study sought to adjust for these factors to better define abnormal growth. STUDY DESIGN: Maternal and infant characteristics from normal pregnancies were correlated with birth weight. A formula was developed and applied to a second group in which we compared perinatal outcomes in normally grown infants with those who were small for gestational age. We compared outcomes between small-for-gestational-age infants defined by the formula with those defined by conventional tables. RESULTS: Infants defined by the formula as small-for-gestational-age were more likely to have morbidity and mortality than those who were normally grown (p < 0.001). Small-for-gestational-age infants defined by the formula had more deaths and adverse outcomes than those defined by gestational age. CONCLUSION: Adjusting birth weight standards for maternal and infant characteristics may improve the prediction of adverse outcomes.

Adult↗

PubMed2005

Fetal/neonatal outcome in abruptio placentae during preterm gestation.

The purpose of this study was to evaluate the fetal/neonatal outcome and to determine the important factors in that outcome, including the use of ultrasonography and fetal heart rate monitoring, in abruptio placentae during preterm gestation. A case-control study was performed using a logistic regression model. Adverse outcome was defined as neonatal death before hospital discharge or a diagnosis of cerebral palsy in surviving neonates. Stillbirth (group 1) occurred in eight of 50 cases of abruptio placentae (16%). Adverse outcome was seen in 11 survivors (11 of 42; 26.2%). The obstetrical disseminated intravascular coagulation (DIC) score in group 1 (11.8 +/- 7.1) was higher than that in the adverse (5.7 +/- 1.3) and satisfactory (5.3 +/- 2.4) outcome groups. A low Apgar score (< 7) at 5 minutes (odds ratio, 19.8; 95% confidence interval, 2.0 to 197.8) was associated with increased risk of adverse outcome in the logistic regression model. Although the obstetrical DIC score was high and may reflect the severity of maternal complications in the stillbirth group, there were no typical ultrasonographic findings and fetal heart rate patterns in abruptio placentae during preterm gestation predicting adverse outcome among survivors.

Adult↗

PubMed1997

Pregnancy outcomes following false-positive multiple marker screening tests.

Pregnancy outcomes in women with a false-positive midtrimester multiple marker screening test (MMST) were reviewed. A genetic database was used to identify all women > or = age 30 who had a MMST at 15-20 weeks of gestation, a targeted ultrasound, and amniocentesis, and complete pregnancy outcome data. All patients with an abnormal fetal ultrasound (US) or karyotype were excluded. The incidence of adverse outcomes (defined as fetal death, preterm delivery, or a birth weight less than the 10th percentile for gestational age), in those women with a positive MMST (risk of Down's syndrome > or = 1:190) was compared to the incidence of adverse outcomes in control women with negative MMST. Chi-square analysis and Fisher's exact tests were used for comparisons as appropriate. Complete data was available from 1135 women. Seventy-seven percent were over age 35. Two hundred and forty-six women (22%) had a positive multiple marker test. No significant differences in outcomes were discovered after comparisons to controls: fetal death 1 of 246 (0.4%) versus 12 of 889 (1.3%), p = 0.32; preterm delivery 32 of 246 (13.0%) versus 147 of 889 (16.5%), p = 0.17; birth weight less than the 10th percentile, 9 of 246 (3.7%) versus 30 of 889 (3.4%), p = 0.83. Our data suggest that women > or = age 30 with a false-positive MMST and a normal midtrimester obstetrical sonogram are not at an increased risk for adverse pregnancy outcomes in later gestation.

Adult↗

PubMed1982

Nifedipine in unstable angina: a double-blind, randomized trial.

We assessed the efficacy of adding nifedipine to the conventional treatment of unstable angina in 138 patients in a prospective, double-blind, randomized, placebo-controlled trial. There was no difference between the two groups in the dose of conventional antianginal medication or in age, prior myocardial infarction, ejection fraction, or other risk factors. Failure of medical treatment (defined as sudden death, myocardial infarction, or bypass surgery within four months) occurred in 43 of 70 patients given placebo and in 30 of 68 given nifedipine. Kaplan-Meier survival-curve analysis of the number and time dependence of treatment failures demonstrated a benefit of nifedipine over placebo (P = 0.03). The benefit was particularly marked in patients with ST-segment elevation during angina (P = 0.02). Side effects (transient hypotension or diarrhea) required withdrawal of the drug from four patients given nifedipine and from one given placebo. We conclude that the addition of nifedipine to conventional therapy is safe and effective in unstable angina.

Adult↗

PubMed1992

A controlled trial comparing continued zidovudine with didanosine in human immunodeficiency virus infection. The NIAID AIDS Clinical Trials Group.

BACKGROUND: Although zidovudine is effective in patients with human immunodeficiency virus (HIV) infection, its efficacy may decline with prolonged use. Didanosine is another inhibitor of HIV reverse transcriptase. We evaluated the effectiveness of changing anti-HIV treatment from zidovudine to didanosine. METHODS: This multicenter, double-blind study involved 913 patients who had tolerated zidovudine for at least 16 weeks. The patients had the acquired immunodeficiency syndrome (AIDS), AIDS-related complex with less than or equal to 300 CD4 cells per cubic milliliter, or asymptomatic HIV infection with less than or equal to 200 CD4 cells per cubic milliliter. They were randomly assigned to receive 600 mg per day of zidovudine, 750 mg per day of didanosine, or 500 mg per day of didanosine. RESULTS: There were significantly fewer new AIDS-defining events and deaths among the 298 subjects assigned to 500 mg per day of didanosine than among the subjects who continued to receive zidovudine (relative risk, 1.39; 95 percent confidence interval, 1.06 to 1.82; P = 0.015). With 750 mg of didanosine, there was no clear benefit over zidovudine (relative risk, 1.10; 95 percent confidence interval, 0.86 to 1.42). The efficacy of didanosine was unrelated to the duration of previous zidovudine treatment. In the two didanosine groups, there were improvements in the number of CD4 cells (P less than 0.001 for both groups) and in p24 antigen levels (P = 0.03 in the 500-mg group; P = 0.005 in the 750-mg group), as compared with the zidovudine group. CONCLUSIONS: Changing treatment from zidovudine to 500 mg per day of didanosine appears to slow the progression of HIV disease.

AIDS-Related Complex↗

PubMed1993

Effect of prenatal ultrasound screening on perinatal outcome. RADIUS Study Group.

BACKGROUND: Many clinicians advocate routine ultrasound screening during pregnancy to detect congenital anomalies, multiple-gestation pregnancies, fetal growth disorders, placental abnormalities, and errors in the estimation of gestational age. However, it is not known whether the detection of these conditions through screening leads to interventions that improve perinatal outcome. METHODS: We conducted a randomized trial involving 15,151 pregnant women at low risk for perinatal problems to determine whether ultrasound screening decreased the frequency of adverse perinatal outcomes. The women randomly assigned to the ultrasound-screening group underwent one sonographic examination at 15 to 22 weeks of gestation and another at 31 to 35 weeks. The women in the control group underwent ultrasonography only for medical indications, as identified by their physicians. Adverse perinatal outcome was defined as fetal death, neonatal death, or neonatal morbidity such as intraventricular hemorrhage. RESULTS: The mean numbers of sonograms obtained per woman in the ultrasound-screening and control groups were 2.2 and 0.6, respectively. The rate of adverse perinatal outcome was 5.0 percent among the infants of the women in the ultrasound-screening group and 4.9 percent among the infants of the women in the control group (relative risk, 1.0; 95 percent confidence interval, 0.9 to 1.2; P = 0.85). The rates of preterm delivery and the distribution of birth weights were nearly identical in the two groups. The ultrasonographic detection of congenital anomalies had no effect on perinatal outcome. There were no significant differences between the groups in perinatal outcome in the subgroups of women with post-date pregnancies, multiple-gestation pregnancies, or infants who were small for gestational age. CONCLUSIONS: Screening ultrasonography did not improve perinatal outcome as compared with the selective use of ultrasonography on the basis of clinician judgment.

Adolescent↗

PubMed1995

Quantitative analysis of heart rate variability.

In the modern industrialized countries every year several hundred thousands of people die due to sudden cardiac death. The individual risk for this sudden cardiac death cannot be defined precisely by common available, noninvasive diagnostic tools like Holter monitoring, highly amplified ECG and traditional linear analysis of heart rate variability (HRV). Therefore, we apply some rather unconventional methods of nonlinear dynamics to analyze the HRV. Especially, some complexity measures that are based on symbolic dynamics as well as a new measure, the renormalized entropy, detect some abnormalities in the HRV of several patients who have been classified in the low risk group by traditional methods. A combination of these complexity measures with the parameters in the frequency domain seems to be a promising way to get a more precise definition of the individual risk. These findings have to be validated by a representative number of patients. (c) 1995 American Institute of Physics.

Journal Article↗

PubMed2001

Coronary stenting in diabetic patients: Results from the ROSETTA registry.

OBJECTIVE: Diabetes mellitus is associated with high rates of restenosis and adverse outcomes after percutaneous transluminal coronary angioplasty (PTCA). It is unclear whether coronary stenting reduces adverse events in diabetic patients after PTCA. Our purpose was to determine whether coronary stenting improves clinical event rates in diabetic patients after PTCA. METHODS: The Routine Versus Selective Exercise Treadmill Testing After Angioplasty (ROSETTA) registry was a prospective multicenter observational study examining functional testing and adverse outcomes after successful PTCA. RESULTS: Among the 791 patients enrolled, 180 were diabetic. A total of 90 diabetics received stents while the remaining 90 patients did not. Baseline clinical characteristics were similar between the 2 groups of patients. However, patients with stents were more likely to have complex lesions, whereas those without stents were more likely to undergo atherectomy and have greater residual coronary stenosis. At 6-month follow-up, the composite end point defined as cardiac death, unstable angina, myocardial infarction, need for repeat PTCA, or coronary artery bypass graft surgery (CABG) occurred in 25.0% of stented and 22.2% of nonstented diabetic patients (P not significant [NS]). A multivariate logistic regression analysis showed that coronary stenting was not associated with a reduced incidence of the composite end point among diabetic patients (odds ratio 0.97, 95% CI 0.46-2.05, P NS). CONCLUSION: Coronary stenting does not improve clinical event rates in diabetic patients after PTCA.

Angioplasty, Balloon, Coronary↗

PubMed2004

Induction of lysosomal membrane permeabilization by compounds that activate p53-independent apoptosis.

The p53 protein activates cellular death programs through multiple pathways. Because the high frequency of p53 mutations in human tumors is believed to contribute to resistance to commonly used chemotherapeutic agents, it is important to identify drugs that induce p53-independent cell death and to define the mechanisms of action of such drugs. Here we screened a drug library (the National Cancer Institute mechanistic set; 879 compounds with diverse mechanisms of actions) and identified 175 compounds that induced caspase cleavage of cytokeratin-18 in cultured HCT116 colon cancer cells at <5 microM. Interestingly, whereas most compounds elicited a stronger apoptotic response in cells with functional p53, significant apoptosis was observed also in p53-null cells. A subset of 15 compounds showing weak or no dependence on p53 for induction of apoptosis was examined in detail. Of these compounds, 11 were capable of activating caspase-3 in enucleated cells. Seven such compounds with nonnuclear targets were found to induce lysosomal membrane permeabilization (LMP). Translocation of the lysosomal proteases cathepsin B and cathepsin D into the cytosol was observed after treatment with these drugs, and apoptosis was inhibited by pepstatin A, an inhibitor of cathepsin D. Apoptosis depended on Bax, suggesting that LMP induced a mitochondrial apoptotic pathway. We conclude that a large number of potential anticancer drugs induce p53-independent apoptosis and that LMP is a mediator of many such responses.

Apoptosis↗

PubMed1996

Molecular ordering of the cell death pathway. Bcl-2 and Bcl-xL function upstream of the CED-3-like apoptotic proteases.

Genetic analyses of Caenorhabditis elegans has identified three genes that function in the regulation of nematode cell death. Mammalian homologs of two of these genes, ced-9 and ced-3, have been identified and comprise proteins belonging to the Bcl-2 and ICE families, respectively. To date, it is unclear where the negative regulators, ced-9 and bcl-2, function relative to the death effectors, ced-3 and the mammalian ced-3 homologs, respectively. Here, the molecular order of the cell death pathway is defined. Our results establish that Bcl-2 and Bcl-xL function upstream of two members of the ICE/CED-3 family of cysteine proteases, Yama (CPP32/apopain) and ICE-LAP3 (Mch3).

Amino Acid Sequence↗

PubMed2006

Factors of severity at admission during an epidemic of dengue 1 in New Caledonia (South Pacific) in 2003.

We report a retrospective study of an epidemic of dengue in New-Caledonia (South Pacific) in 2003 among adult inpatients. The aim was to establish clinical and biological criteria for the severity of the infection at the time of admission. During 7 months, all inpatients older than 15 y having a laboratory-confirmed diagnosis of dengue fever (IgM or PCR) were included (n=170). Two groups were defined: severe cases (death and/or transfer to intensive care unit, n=24) and benign cases (n=146). Data were analysed using Epi-Info software. Univariate analysis showed that shock, haemorrhage and neurological complications were significantly more frequent in serious cases, respectively 37.5% vs 0.7%, 62.5% vs 32.2%, 25% vs 9.6% (p<0.05). Relevant biological criteria were: creatinine > 140 micromol/l (OR 12 (95% CI 3.93-37.44)), free bilirubin > 18 micromol/l (OR 12.69 ( 95% CI 2.88-59.5)), amylase > 220 UI/l (OR 27.34 (95% CI 4.57-210)) and platelets < 45,000/mm3 (OR 4.35 (95% CI 1.43-14.2)) with p<0.005 (VPP = 100% for association of 3 criteria). We suggest this combination of 4 biological criteria inclines to severity.

Amylases↗

PubMedDate not supplied

Birth spacing, breastfeeding, and early child mortality in a traditional Indian society: a hazards model analysis.

There are few studies of the interrelationships among breastfeeding, child spacing, and child mortality in traditional societies that incorporate extensive controls for social and demographic characteristics of the mother and child. In this paper, we investigate the impact of breastfeeding and the length of the preceding birth interval on early child mortality (defined as a death in the first two years of life) using data from a traditional society of India. Multivariate hazards models are used to analyze the data. Most prior analyses related the impact of breastfeeding duration to the duration of child survivability by taking breastfeeding as a fixed covariate. The present study has a methodological focus in the sense that breastfeeding information from retrospective survey data is treated as a time-dependent covariate both as a status variate as well as a duration--with empirical findings compared across the two specifications. The effects of postpartum amenorrhoea and various other demographic and socioeconomic characteristics of mother and child are also studied. The results suggest that breastfeeding duration has a strong impact in reducing the relative risk of early child mortality; but it does not explain the effect of the length of the preceding birth interval on early child mortality.

Birth Intervals↗

PubMed2004

Yeast Miro GTPase, Gem1p, regulates mitochondrial morphology via a novel pathway.

Cell signaling events elicit changes in mitochondrial shape and activity. However, few mitochondrial proteins that interact with signaling pathways have been identified. Candidates include the conserved mitochondrial Rho (Miro) family of proteins, which contain two GTPase domains flanking a pair of calcium-binding EF-hand motifs. We show that Gem1p (yeast Miro; encoded by YAL048C) is a tail-anchored outer mitochondrial membrane protein. Cells lacking Gem1p contain collapsed, globular, or grape-like mitochondria. We demonstrate that Gem1p is not an essential component of characterized pathways that regulate mitochondrial dynamics. Genetic studies indicate both GTPase domains and EF-hand motifs, which are exposed to the cytoplasm, are required for Gem1p function. Although overexpression of a mutant human Miro protein caused increased apoptotic activity in cultured cells (Fransson et al., 2003. J. Biol. Chem. 278:6495-6502), Gem1p is not required for pheromone-induced yeast cell death. Thus, Gem1p defines a novel mitochondrial morphology pathway which may integrate cell signaling events with mitochondrial dynamics.

Actins↗

PubMed2000

Long-term outcome and treatment modifications in a prospective cohort of human immunodeficiency virus type 1-infected patients on triple-drug antiretroviral regimens. Triest Cohort Investigators.

We designed a cohort in order to assess the long-term effects of triple-drug antiretroviral combinations in 608 patients infected with human immunodeficiency virus type 1 (HIV-1). We recruited patients who had been previously treated with nucleoside analogues as well as treatment-naive patients who were starting triple-drug antiretroviral combinations consisting of nucleoside analogues, either alone or in combination with a protease inhibitor. After a median follow-up time of 22 months, the incidence rates of acquired immune deficiency syndrome-defining events and death were, respectively, 6.9 (95% confidence interval [CI], 5.3-8.8) and 2.9 (95% CI, 1.9-4.2) per 100 person-years. Advanced clinical stage of disease (P=.004), a low CD4(+) cell count (P=.002), and a low quality-of-life score (P=.001) at baseline were independent predictors of clinical progression. The initial triple-drug combination was modified a total of 647 times in 321 patients. The only independent predictor of treatment modification was previous exposure to a nucleoside analogue in patients who did not receive a new nucleoside analogue at inclusion (P=.001). Plasma HIV RNA values below 500 copies/mL were obtained in 88% of the treatment-naive patients and in 57% of the previously treated patients (P<.001). Compared with previously treated patients who received > or = 1 new nucleoside analogue at enrollment, previously treated patients who did not receive a new nucleoside analogue at enrollment were twice as likely to have plasma HIV RNA values >500 copies/mL at the last visit (adjusted odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.8), and the antiretroviral-naive patients were significantly less likely to have plasma HIV RNA values >500 copies/mL at the last visit (adjusted OR, 0.2; 95% CI, 0.1-0.4).

Acquired Immunodeficiency Syndrome↗

PubMed2001

Long-term clinical outcome of human immunodeficiency virus-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen.

Within a prospective cohort of 150 human immunodeficiency virus (HIV)-infected patients who began first-line protease inhibitor therapy in 1996, the outcome of 42 patients with discrepant virologic and immunologic responses to antiretroviral treatment at 12 months was analyzed at 30 months of treatment. The incidence of AIDS-defining events and deaths (14%) in the group of patients with immunologic responses in the absence of a virologic response was higher than that in full-responder patients (2%); yet, the incidence in this group was lower than that in patients with no immunologic response, despite a virologic response (21%), and was lower than that in patients without an immunologic or virologic response (67%; P<.0001, log-rank test). Differences in outcome were significant (relative risk, 6.9; 95% confidence interval, 1.9-39.3) when factors for progression were compared with those of responder patients. The results support the relevance of the CD4 cell marker over plasma HIV load for predicting clinical outcome in patients who do not achieve full immunologic and virologic responses.

Adult↗