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Biomedical subjects

D J Flannery

Publications and source records attributed to D J Flannery.

14 recordsLinked to original sources

Violence exposure, psychological trauma, and suicide risk in a community sample of dangerously violent adolescents.

OBJECTIVE: To examine violence exposure, violent behaviors, psychological trauma, and suicide risk in a community sample of dangerously violent adolescents by comparison with a matched community sample of nonviolent adolescents. METHOD: Anonymous self-report questionnaires were administered in the 1992-1993 school year to students in grades 9 through 12, in six public high schools located in Ohio and Colorado (N = 3,735). From this sample, 484 adolescents (349 males, 135 females) who reported attacking someone with a knife or shooting at someone within the past year (i.e., dangerously violent adolescents) were drawn. Four hundred eighty-four controls were also selected and matched on gender, age in years, ethnicity, area of residence, and family structure. RESULTS: Dangerously violent adolescents reported higher levels of exposure to violence and victimization than did matched controls. Dangerously violent females were more likely to score in the clinical range of depression, anxiety, posttraumatic stress, anger, and dissociation than were control females and violent males; they also had significantly higher levels of suicide potential. CONCLUSIONS: Students who have been known to commit violent acts should be adequately assessed for violence exposure and symptoms of psychological trauma, with special attention given to the suicide potential of violent females.

Adolescent↗

The relationship between children's threats of violence and violent behaviors.

BACKGROUND: We sought to examine the relationship between students' threats of interpersonal violence and self-reported violent behaviors. METHODS: Anonymous self-report questionnaires were administered to students in grades 3 through 12 in schools located in Colorado, Arizona, and Ohio. A survey of 9487 students from 33 public schools was performed. Ages ranged from 7 to 19 years. Across the 3 samples, the percentage of African Americans ranged from 6% to 35%, whites from 31% to 57%, and Hispanics from 5% to 51%. RESULTS: Multivariate logistic regression analyses revealed that threatening others infrequently or frequently (compared with not threatening others) was significantly associated with violent behaviors. Students who infrequently threatened were about 3 to 4 times more likely to report exhibiting each of the violent behaviors than students who did not threaten others (odds ratio [OR] = 4.08-5.86). The relationship between frequently threatening others and violent behaviors was especially strong (OR = 7.19-24.30) and highest for the most severe forms of violence, knife attacks (OR = 15.39-24.30) and shootings (OR = 18.42). CONCLUSIONS: Findings suggest that students' threats of harm toward others should be taken seriously, and that policies and procedures should be developed to ensure that children who threaten others receive proper assessment and management. Arch Pediatr Adolesc Med. 2000;154:785-790

Adolescent↗

Who are they with and what are they doing? Delinquent behavior, substance use, and early adolescents' after-school time.

The relationship among after-school time, parental monitoring, and problem behavior was examined in a sample of 1,170 early adolescents. Those spending unsupervised time with peers reported higher levels of aggression, delinquency, substance use, and susceptibility to peer pressure, and lower levels of parental monitoring, than did adolescents at home with parents. Adolescents home alone after school were similar to those who spent time with adults or in school activities.

Adolescent↗

Contributors to violent behavior among elementary and middle school children.

OBJECTIVE: To examine the relative contributions of exposure to violence, parental monitoring, and television-viewing habits to children's self-reported violent behaviors. The study hypothesized that: 1) children's exposure to violence would be associated positively with self-reported violent behaviors; 2) parental monitoring would be associated negatively with children's violent behaviors; and 3) the number of daily television-viewing hours and a preference for watching violent television shows would be associated positively with children's violent behaviors. METHODS: The study used a survey design with an anonymous self-report questionnaire administered to students (grades 3-8) in 11 public schools. A total of 2245 students participated in the study, representing 80% of the students attending the participating schools during the survey. The subjects were from 7 to 15 years of age; 51% were male, 57% were white, 33% percent were black, and 5% were Hispanic. RESULTS: Hierarchical multiple regression analysis of the total sample revealed that the combination of demographic variables, parental monitoring, television-viewing habits, and exposure to violence explained 45% of students' self-reported violent behaviors. Violence exposure and parental monitoring were the most influential contributors in explaining children's violent behaviors, accounting for 24% and 5% of the variance in violent behaviors, respectively. CONCLUSIONS: All three hypotheses were supported. A significant association was demonstrated linking violence exposure, lack of parental monitoring, and television-viewing habits with children's self-reported violent behaviors within a diverse sample of elementary and middle school students. Our findings support the importance of parental monitoring of children and emphasize the need to identify and to provide services to youth who are exposed to violence.

Adolescent↗

Post-traumatic stress disorder in children and adolescents exposed to violence.

The common biopsychosocial sequelae of violence exposures are reviewed, with a focus on post-traumatic stress disorder in developmental, clinical, and familial contexts. Challenges to assessment are reviewed, and implications for prevention and treatment are presented. Pediatricians have an essential role to play in secondary and tertiary prevention through the use of anticipatory guidance and victimization as a marker of developmental risk.

Adolescent↗

Venlafaxine in adults with attention-deficit/hyperactivity disorder: an open clinical trial.

BACKGROUND: It is becoming commonly recognized that adults suffer from attention-deficit/hyperactivity disorder (ADHD). Since medications used in the past of treat adults with ADHD may be ineffective or poorly tolerated by some patients, it is important to determine if newly available medications can safely ameliorate symptoms of ADHD in adults. METHOD: An open clinical trial was undertaken to examine whether venlafaxine was safe and effective in the treatment of adults with ADHD. Ten subjects who met DSM-IV criteria for ADHD were enrolled in this 8-week trial. Individuals were started on 37.5 mg of venlafaxine b.i.d. If moderate ADHD symptoms persisted at the end of Week 4, the dose of venlafaxine was increased to 75 mg b.i.d. Assessments of ADHD symptomatology included the ADHD Rating Scale, Self-Report Version (ARS) and the Clinical Global Impressions (CGI) scale. RESULTS: Nine patients completed the study. At the end of the study, 7 patients were receiving 37.5 mg b.i.d. of venlafaxine. Repeated measures ANOVA demonstrated that treatment with venlafaxine was associated with significant reductions in ADHD symptomatology (p < .02 for the ARS; p < .005 for the CGI). Of the 9 subjects who completed the trial, 7 were considered responders. Venlafaxine was well tolerated, and most patients experienced only mild side effects. CONCLUSION: Venlafaxine may be a promising agent for the treatment of ADHD in adults. Controlled clinical trials are needed to further examine this issue.

Adolescent↗

An elementary school substance abuse prevention program: teacher and administrator perspectives.

Teachers and administrators from a large, diversified school district participated in a survey of perceived satisfaction, effectiveness, and degree of implementation of Project Pride, a substance abuse prevention program. As expected, degree of satisfaction with program content was consistently related to how beneficial and valuable teachers perceived the program to be for their students. The age appropriateness of materials and degree of difficulty in implementing activities were also significantly related to how much students benefitted from the program. Neither perceived support of administrators nor teacher participation in training was related to level of implementation or teacher satisfaction. The need to gather teacher and administrator perspectives about substance use prevention programs is discussed, as well as steps to be taken to maximize implementation of prevention curricula in elementary schools.

Adult↗

Modulation of the cell cycle-dependent cytotoxicity of adriamycin and 4-hydroperoxycyclophosphamide by novobiocin, an inhibitor of mammalian topoisomerase II.

Centrifugal elutriation was used to obtain synchronized cell populations in various cell cycle phases without prior growth-perturbing manipulation. Treatment of these subpopulations with novobiocin (NOVO), a putative inhibitor of the mammalian topoisomerase II enzyme, revealed a unique cell cycle phase-dependent cytotoxicity for this agent. At a concentration of 0.3 mM, NOVO was cytotoxic only to a specific cell subpopulation in the G1-S phase boundary. Cells in other cell cycle phases were completely unaffected. Additionally, S and G2M phase cells progressed through the cell cycle relatively unaffected by NOVO but were blocked at the G1-S boundary. NOVO treatment protected tumor cells from Adriamycin (ADR)-induced lethality but sensitized them to the toxic action of 4-hydroperoxycyclophosphamide, and alkylating agent. These opposing effects of NOVO were demonstrated in all of the four tumor cell lines investigated: A431 and HEp3 (derived from human squamous cell carcinomas); MLS, a human ovarian cancer cell line; and a Chinese hamster ovary cell line. The degree of protection against ADR was the greatest for S-phase cells, intermediate for cells in early G1 and M phases, and the least for late G1 cells. This cell cycle-dependent protection by NOVO, which is identical to the cell cycle-dependent cytotoxicity of ADR, was consistent with the idea that NOVO interfered directly with the cell-killing mechanism of ADR. In contrast, even though the cytotoxic activity of 4-hydroperoxycyclophosphamide exhibited significant cell cycle dependency, NOVO enhanced 4-hydroperoxycyclophosphamide lethality equally for all cell cycle phases.

Animals↗

Anistreplase in early acute myocardial infarction and the one-year follow-up.

Of consecutive patients seen with first myocardial infarction (88 of whom were treated out-of-hospital by mobile coronary care staff), 139 received 30 units of intravenous anistreplase at a mean of 101 minutes (range 35-180) from onset of symptoms. Thrombolysis in myocardial infarction patency grade 2 or 3 was found in 76/91 (83.5%) patients. At 3-4 months after hospital discharge, the mean global left ventricular ejection fraction and mean infarct-related regional third ejection fraction declined with increasing delay to anistreplase. For the first, second and third hour administrations, global ejection fraction was 54%, 50% and 45% (P = 0.002) and for regional third ejection fractions 49%, 43% and 41% (P = 0.02) respectively. Of the patients, 130 were reviewed at approximately 1 year: reinfarction had occurred in 9, 6 had undergone coronary angioplasty and 1 had coronary arterial bypass grafting performed since discharge. Mean global left ventricular ejection fraction was 52% and mean infarct-related regional third ejection fraction was 51%. Thus, intravenous anistreplase induces high rates of arterial patency. Global and regional third ejection fractions decline with increasing delay in the time of administration of anistreplase. Mortality and morbidity is low in the first year.

Adult↗

Prediction of tumour sensitivity to 4-hydroperoxycyclophosphamide by a glutathione-targeted assay.

In an attempt to develop an assay to predict patient tumour response to cyclophosphamide (CP), the feasibility of using a glutathione-targeted assay to assess the in vitro chemosensitivity of tumour cells to 4-hydroperoxycyclophosphamide (4-OOH-CP), an activated congener of CP, was evaluated. A panel of 19 human and three murine tumour cell lines was used. These consisted of three main categories of tumour types, viz. ovarian, lung and squamous cell carcinoma. The major finding was that the occurrence of a significant reduction of tumour cell reproductive capacity was always accompanied by substantial depletion of cellular glutathione (GSH) content, and vice versa. Plots of % GSH depletion versus clonogenic cell survival demonstrated highly significant correlation (r = 0.90-0.91; P less than 0.01). It was determined that for in vitro tumour cell lines, a GSH depletion to 40% of initial content may serve as a cut-off criterion for chemosensitivity to 4-OOH-CP. This degree of GSH depletion is indicative of clonogenic cell survival of approximately 1% (95% confidence limits = 3 x 10(-5)-1.6 x 10(-2)). The relationship between steady state GSH content and intrinsic sensitivity to 4-OOH-CP was also evaluated. The GSH concentration of the tumour cell lines ranged from 1.3-21.2 x 10(-18) moles microns-3; chemosensitivity to 4-OOH-CP, in terms of IC99, was in the range of 5.0-87.1 microM. A good correlation was observed between these two parameters (r = 0.85, P less than 0.02). These results suggest that GSH plays an important role in determining the therapeutic efficacy of 4-OOH-CP in the treatment of cancer. It is uncertain, however, whether a high tumour steady state GSH content in itself is sufficient to cause therapeutic failure in patients.

Animals↗

Thrombolytic therapy within one hour of the onset of acute myocardial infarction.

Between 1986 and 1988, 239 consecutive patients with acute myocardial infarction received thrombolytic therapy up to 285 minutes after onset of symptoms; in 39 (17 with anterior infarction, 21 inferior, one lateral infarction) recombinant tissue plasminogen activator or anistreplase was administered a mean of 51 minutes (range 20-60 minutes) after the onset of symptoms. The patency rates (26 of 30; 87 per cent), rapid ST segment resolution (36 of 38; 95 per cent) and QRS score of less than or equal to 3 (28 of 38; 74 per cent) were statistically significantly higher for those seen and treated in the first hour in comparison with those seen and treated later. For those treated within the first hour mean peak creatine kinase was 1264 U/l for those with TIMI grade 2 or 3 (partial or complete perfusion) compared with 3005 U/l for those with TIMI grade 0 or 1 (no perfusion or penetration without perfusion) (p = 0.02): mean peak creatine kinase-MB for those with TIMI grade 2 or 3 perfusion was 115 U/l compared with 312 U/l for those with TIMI grade 0 or 1 (p = 0.01). Four of the 39 patients developed ventricular fibrillation following thrombolytic therapy, three within 24 hours of infarction and one following reinfarction on day 15. There were no significant bleeding complications. One patient died. Thrombolytic therapy within 1 hour of the onset of symptoms led to a very high angiographic patency rate, rapid ST segment resolution with preservation of left ventricular function. This therapy is without significant complications.

Anistreplase↗

A double blind placebo controlled study of early and late administration of recombinant tissue plasminogen activator in acute myocardial infarction.

Within four hours of the onset of acute myocardial infarction 57 consecutive patients were randomised blindly to infusion of 150 mg recombinant tissue plasminogen activator (rt-PA) (group 1) over five hours or placebo (group 2) when they were first seen outside hospital or in the accident and emergency department. When they were admitted to the coronary care unit patients in group 1 also had placebo infused and those in group 2 were treated with rt-PA as well as placebo. Treatment with rt-PA started at a mean of 119 minutes (range 38-235) after the onset of pain in group 1 and 187 minutes (range 80-285) after the onset of pain in group. In 19 (79%) of 24 in group 1 and 16 of 25 (64%) in group 2 cardiac catheterisation 10-14 days after infarction showed thrombolysis in myocardial infarction grades 2 or 3. There was mean percentage shortening of the infarct related segments (Leighton method) of 16% in group 1 and 10.3% in group 2. For patients with anterior infarction mean percentage shortening was 20.5% in group 1 and 12.2% in group 2. Although there was no significant difference in global ejection fraction as assessed by contrast ventriculography or radionuclide ventriculography the infarct related regional third ejection fraction (a measure of the function of the territory of the affected coronary artery) was significantly improved by early treatment (41% group 1 and 28% group 2). Assessment of infarct size by the QRS scoring method of Palmeri showed QRS score less than or equal to 15/25 patients in group 1 and 8/27 in group 2. Nine patients developed 11 episodes of ventricular fibrillation; all patients in whom ventricular fibrillation developed during treatment with rt-PA were successfully resuscitated. There was no clinically significant bleeding. In seven (12%) patients clinical and electrocardiographic criteria suggested reocclusion. Five patients died from cardiac causes. Prehospital administration of rt-PA was feasible and significantly reduced the delay before thrombolysis was started. Earlier treatment improved myocardial function in the the infarct area and reduced the infarct size.

Adult↗

A randomised dose ranging study of recombinant tissue plasminogen activator in acute myocardial infarction.

To assess the thrombolytic efficacy and the effect on the systemic fibrinolytic system of recombinant tissue plasminogen activator doses of 20 mg, 50 mg, and 100 mg were compared in a randomised study. Tissue plasminogen activator was infused intravenously over 90 minutes in 50 consecutive patients with acute myocardial infarction of four hours' duration or less; on average the infusion was started 135 minutes (range 20 to 240) after the onset of pain. The affected artery was patent at the end of the 90 minute infusion in 14/17 (82%) of those who received 100 mg, 12/17 (71%) of those who received 50 mg, and 8/16 (50%) of those who received 20 mg. Regardless of dose, reperfusion rates were significantly better for patients treated within two hours of the onset of symptoms (81%) than for those treated in the third and fourth hours (54%). At the end of the infusion serum fibrinogen concentrations fell to 86% of the preinfusion value after 20 mg, 75% after 50 mg, and 63% after 100 mg, and similar dose dependent changes occurred in plasminogen, (alpha 2 anti-plasmin, and fibrinogen and fibrin degradation products. The mean infarct related regional third ejection fraction was 46% for patients with grade 2 or 3 reperfusion and 35% for those with grade 0 or 1. Ventricular fibrillation occurred in six (12%) patients during the infusion of tissue plasminogen activator, but no late ventricular fibrillation occurred. Bleeding was minimal, reocclusion occurred in three patients, and four patients died from cardiac causes. Recombinant tissue plasminogen activator is an effective thrombolytic agent which produces better reperfusion rates after a 50 or 100 mg dose than after a 20 mg dose. The effect on the systemic fibrinolytic system is dose dependent. Successful reperfusion results in improvement of left ventricular function.

Adult↗

Peacebuilders: a theoretically driven, school-based model for early violence prevention.

PeaceBuilders is a schoolwide violence-prevention program for elementary schools (K-5). A coalition of the Pima County Community Services Department, University of Arizona, and Heartsprings, Inc., (a Tucson-based company) are conducting a formal evaluation. Children who grow up to commit acts of violence show cognitive, social, and imitative differences from their peers. These characteristics can be ameliorated, most successfully through interventions that begin at an early age and involve multiple segments of the child's social experiences and interactions. PeaceBuilders activities are built into the school environment and the daily interactions among students, teachers, and administrative staff, all of whom are taught a common language and provided models of positive behavior, environmental cues to signal such behavior, opportunities to rehearse positive behavior, and rewards for practicing it. Four schools, one from each of four matched pairs, were randomly assigned to begin PeaceBuilders in Year 1. The remaining four schools begin in Year 2. Outcome assessments include student self-reports, standardized teacher reports, playground observations, and school and law enforcement records. Process assessments include school observations and surveys of teacher practices and satisfaction. Surveys were completed by 2,736 children. The sample is about 55% Hispanic, 26% Anglo, 14% Native American, and 4% African American. Among children in grades 3-5, during the past week 15% had been sent to the office for disciplinary problems, 13% tried to start a fight 27% hit someone, and 12% reported being threatened with a gun or knife. Violent behaviors and experiences are common among the studied children. A valid evaluation is underway of PeaceBuilders.

Age Factors↗