Childhood Behavior Problems and Adolescent Sexual Risk Behavior: Familial Confounding in the Child and Adolescent Twin Study in Sweden (CATSS)

ObjectivePrevious studies have found associations between childhood behavior problems and adolescent sexual risk behavior. Using a quasi-experimental approach, we examined the extent to which this association may be due to between-family differences (i.e., unmeasured familial confounds) not adequately explored in prior research.MethodsWe used data from a longitudinal, population-based cohort of young twins in Sweden (first assessment: age 9 or 12 years; second assessment: age 15; n = 2,388). We explored the nature of the association between symptom scores for attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) at age 9 or 12 and the likelihood of having had sexual intercourse and number of sexual partners by age 15. Two-level mixed-effects models were used to estimate the effect of symptom score on each outcome after controlling for potential unmeasured familial confounds.ResultsHigher ADHD, ODD, and CD scores were associated with significantly increased likelihood of sexual intercourse by age 15. Higher ADHD and ODD scores were also associated with increased number of sexual partners. After controlling for unmeasured familial confounds, however, behavior problems were no longer significantly associated with either outcome.ConclusionThe association between childhood behavior problems and sexual risk behaviors may be due to characteristics shared within families. Hence, prevention strategies aimed at reducing these behaviors might need to address broader risk factors that contribute to both behavior problems and a greater likelihood of sexual risk behavior.     

Kinase requirements in human cells: V. Synthetic lethal interactions between p53 and the protein kinases SGK2 and PAK3

Cervical carcinomas are initiated through a series of well-defined stages that rely on the expression of human papillomavirus (HPV) oncogenes. A panel of 100 small hairpin RNAs that target essential kinases in many tumor types was used to study the stepwise appearance of kinase requirements during cervical tumor development. Twenty-six kinases were commonly required in three cell lines derived from frank carcinomas, and each kinase requirement was traced to the specific stage in which the requirement emerged. Six kinases became required following HPV-induced immortalization, and the requirement for two kinases, SGK2 and PAK3, was mapped to the inactivation of p53 in primary human epithelial cells. Loss of the p53 tumor suppressor in other primary epithelial cells also induced dependence on SGK2 and PAK3. Hence, SGK2 and PAK3 provide important cellular functions following p53 inactivation, fulfilling the classical definition of synthetic lethality; loss of p53, SGK2, or PAK3 alone has little effect on cell viability, whereas loss of p53 together with either SGK2 or PAK3 loss leads to cell death. Whereas tumor suppressor gene mutations are not directly druggable, other proteins or pathways that become obligatory to cell viability following tumor suppressor loss provide theoretical targets for tumor suppressor-specific drug discovery efforts. The kinases SGK2 and PAK3 may thus represent such targets for p53-specific drug development.     

Use of abciximab and tirofiban in patients with peripheral arterial occlusive disease and arterial thrombosis

Acute peripheral arterial occlusive disease is an important factor affecting the mobility and mortality rate of elderly patients. Catheter-guided arterial thrombolysis in these patients has its limitations: long lysis times, early occlusions, and high restenosis rates. The study investigated whether the use of tirofiban has the same favorable effect as the glycoprotein (GP) IIb/IIIa receptor antagonist abciximab and whether lysis times can be shortened and the disease course positively influenced by these substances. Sixty patients were randomly assigned to 2 groups. Each group received 5 mg recombinant tissue-type (rt-PA) plasminogen activator by slow intra-arterial injection for 10 minutes followed by 5 mg rt-PA per hour and 500 IU heparin per hour IV. After randomization 1 group received a bolus of 0.25 mg abciximab per kg body weight followed by 10 mg per minute IV for 12 hours (heparin was reduced to 250 IU/hr). The other group received a bolus of 0.4 microg tirofiban per kg body weight as well as postinterventional medication with 0.1 microg tirofiban per minute and kg body weight for 24 hours. During medication with GP IIb/IIIa inhibitor, the patients received a reduced heparin dosage for 24 hours. After 24 hours both groups received 200 mg aspirin orally and full heparinization controlled on the basis of the partial thromboplastin time. The following efficacy criteria were analyzed: rehospitalization events, reintervention events, and amputations within 6 months. Secondary endpoints were changes in the Fontaine stage, the crurobrachial index, the distance to claudication, and the duration of local arterial lysis. No significant differences were found between the abciximab and tirofiban groups in terms of the rehospitalization, reintervention, or amputation rates, nor were there any group differences in the total number of events. The secondary parameters, such as the crurobrachial index, distance to claudication, and Fontaine stage, also showed no significant differences between the 2 groups within 6 months. The duration of lysis was significantly shorter in the abciximab group. Major bleeding events did not occur in either group. With regard to the adverse effect rate, there were no significant differences between the 2 groups. Both abciximab and tirofiban can be used successfully in patients with peripheral arterial occlusive disease and arterial thrombosis.     

Wirbelfrakturen und Spondylitis deformans

Ohne Zusammenfassung     

Short- and long-term results of abciximab versus aspirin in conjunction with thrombolysis for patients with peripheral occlusive arterial disease and arterial thrombosis

Acute peripheral occlusive arterial disease is an important cause of morbidity and mortality, particularly among older persons. Catheter-directed thrombolytic therapy is the treatment of choice but has limitations: long lytic times, occlusions refractory to thrombolysis, and a high rate of restenosis. We conducted a pilot study to evaluate the use of the platelet GP IIb/IIIa receptor antagonist abciximab versus aspirin in conjunction with thrombolysis in patients with acute peripheral occlusive arterial disease associated with arterial thrombosis. A total of 84 patients were randomized into two equal groups to receive 5 mg recombinant tissue plasminogen activator intravenously and 500 IU heparin/hour along with either 500 mg acetylsalicylic acid or a bolus of 0.25 mg/kg abciximab followed by 10 microg/min abciximab over 12 hours (heparin reduced to 250 IU/hour). Primary efficacy criteria included the number of rehospitalizations, reinterventions, and amputations during the following 6 months. Secondary endpoints were the changes in the Fontaine stage, Bollinger index (vessel occlusion), ankle-to-brachial ratios, distance to claudication after 6 months, and the duration of the initial local lysis treatment. Adjunctive use of abciximab reduced the rates of rehospitalization, reinterventions, and amputations versus results with the use of aspirin (10 vs 14 occurrences, respectively; 9 vs 11; 3 vs 5; when summed, intergroup difference p < 0.05). Secondary peripheral occlusive arterial disease variables became highly significant versus aspirin (p < 0.001 or greater) at 3 and 6 months after treatment. The duration of lysis was markedly shorter upon addition of abciximab versus aspirin (75 vs 110 min; p < 0.001). No major bleeding complications or embolisms occurred. These preliminary results indicate that abciximab may have a useful role when used adjunctively with a thrombolytic agent in older persons with acute peripheral occlusive arterial disease and arterial thrombosis.