Clinical experience of smoking cessation advice in hospital trauma units

Introduction  

Cigarette smoking is increasingly well recognized as an inhibiting factor in fracture healing, and risk factor for non-union. We assessed whether adequate smoking cessation advice and support was given to cigarette smokers undergoing fracture management, based upon the United States Public Health Service ‘Five As’ Smoking Cessation Guidelines—evidence-based guidelines outlining effective strategy to promote smoking cessation, by taking a smoking history, advising the patient to stop smoking, assessing motivation to stop and facilitating cessation via support groups and pharmacological interventions (Ask, Advise, Assess, Assist, Arrange).     

Germline mutations in RAD51, RAD51AP1, RAD51B, RAD51C,RAD51D, RAD52 and RAD54L do not contribute to familial chronic lymphocytic leukemia.

While familial predisposition to B-cell chronic lymphocytic leukemia (CLL) is well recognized no gene which when mutated in the germline has been unambiguously shown to confer susceptibility to the disease. An approach based on mutation screening methods targeted to coding regions of candidate genes offers an attractive strategy for the identification of rare disease-causing alleles. The RAD genes participate in the cellular response to DNA double strand breaks, detecting DNA damage, activating cell cycle checkpoints and apoptosis. Defects in members of these genes are linked to increased chromosomal instability and in lymphoma predisposition, thereby representing strong candidate susceptibility genes a priori. To examine this proposition we screened 75 familial CLL probands for germline mutations in this set of genes. No overt pathogenic mutations were identified. These findings indicate that germline mutations in RAD51, RAD51AP1, RAD51L1, RAD51L3, RAD52 and RAD54L are unlikely to be causal of an inherited predisposition to CLL.     

Increased high-affinity nicotinic receptor-binding in rats exposed to lead during development

Receptor autoradiography and membrane radioligand-binding assays were used to determine the expression of nicotinic cholinergic receptors in the brains of weanling rats exposed to low-levels of lead (Pb) during development. Nicotinic receptors were identified with the frog toxin epibatidine (EB) that binds with high affinity to a variety of receptors containing and β subunits. Rat pups were exposed to Pb from their mothers given 750-ppm Pb in the diet beginning on gestational day 0 through postnatal day (PN) 21. Blood Pb levels ranged from 36.5 to 46.5 μg/dl in the PN21 pups, and this exposure did not alter their body weight when compared to control rats. Several brain regions identified by autoradiographic studies as having significant binding of EB were dissected from control and Pb-treated pups and used in saturation-binding experiments with membrane preparations to determine the affinity constant (K_d) and maximal-binding capacity (B_max) of [³H]EB. Results indicate that the B_max of [³H]EB was increased in several brain regions in Pb-treated rat pups, without a significant effect on K_d estimates. [³H]EB-binding to membranes from untreated rats was not affected by in vitro exposure to 20-μM Pb, indicating that the effect of Pb on [³H]EB-binding in vivo was not likely due to direct influence of free Pb remaining in the tissue at the time of assay. The data therefore suggest that expression of nicotinic receptors that bind [³H]EB were increased by developmental exposure to Pb. Several possible mechanisms for these effects and the potential toxicological significance are discussed.     

Strategies to identify disease genes

The correlation between genes and disease began in earnest in the early 1900s with the identification of Mendelian-like inheritance of "inborn errors of metabolism." Since then, the ever-broadening field of genetics has been established as one of the most important and groundbreaking branches of science and medicine to date. With the announcement of a "working draft" sequence of the human genome in 2001, the vast array of both genomic and expressed sequence information available in the public databases alone has meant that the concept of hunting for genes is evolving. Nowadays, researchers can substitute many labor-intensive hours in the lab for less time searching on the World Wide Web. Specialization within genetics has been continuously providing subsets of the genre such as genomics, pharmacogenetics, chemogenomics, gene therapy, proteomics and functional genomics, all of which are based on the fundamental starting block, the gene. This review aims to summarize both traditional and current strategies for identifying susceptibility and monogenetic disease genes and describes how these strategies have evolved in tune with the ever-expanding wealth of information now available at our fingertips.     

Clinical implications of pervasive manic symptoms in children.

BACKGROUND: Prior investigations of cross-informant agreement among parents, teachers, and clinicians about externalizing and internalizing problems have not directly addressed agreement about manic symptoms. METHODS: We identified three groups from a large cohort of youths, aged 8-12 years, treated on an inpatient unit. All 108 participants met criteria for an externalizing disorder, based on a semi-structured diagnostic interview. Of these, 49 did not have manic symptoms endorsed by either the parent or a teacher; 34 had manic symptoms reported by the parent only, and 25 had pervasive manic symptoms (i.e., corroborated by both sources). RESULTS: The "corroborated mania" group consistently showed the most disruptive behavior on the inpatient unit, the worst behavior problems on multiple scales, and the longest admission durations. The "parent-only" group scored in the midrange on all of these measures, with group differences typically representing small to medium effect sizes. The "externalizing only" group consistently scored lowest on all dependent measures, with the differences representing large to extremely large effects when compared with the corroborated mania group and medium effects as compared with the parent-only group. CONCLUSIONS: Youths for whom multiple informants report manic symptoms appear likely to have more severe symptom presentation and more complicated, refractory courses than do youths without manic symptoms.     

Psychosis in bipolar disorder: phenomenology and impact on morbidity and course of illness

Although psychosis is common in bipolar disorder, few studies have examined the prognostic significance of psychotic features. In addition, some studies suggest that the presence of mood-incongruent psychosis, in particular, is associated with poorer outcome compared with mood-congruent psychosis. We assesses the phenomenology and prevalence of mood-congruent and mood-incongruent psychotic symptoms in 352 patients with bipolar I disorder participating in the Stanley Foundation Bipolar Treatment Network. We compared the demographic and clinical features, and measures of psychosocial and vocational functioning in patients with and without a history of psychosis. The phenomenology of psychosis in this cohort of patients with bipolar disorder was similar to that reported in earlier studies and supported the lack of diagnostic specificity of any one type of psychotic symptom. There were no significant differences between patients with and without a history of psychosis on any demographic, psychosocial, vocational, or course of illness variables. Only family history of bipolar disorder was significantly more common in patients with nonpsychotic bipolar disorder compared to patients with a history of psychosis. Among bipolar patients with a history of psychosis, only the proportion of women and lifetime prevalence rates of anxiety disorders occurred significantly more in patients with mood-incongruent delusions. In this large cohort of outpatients with bipolar I disorder, neither a history of psychosis nor of mood-incongruent psychosis had prognostic significance at entry into the Network. The lack of observable prognostic impact may have been, in part, due to the relatively high morbidity and poor functional outcome of a substantial portion of the total cohort.     

Arterial ischemic strokes in infants and children: an overview of current approaches

Stroke in children is increasingly recognized. The incidence exceeds 8 per 100,000 per year. Important differences in stroke in newborns and children compared with adults, as well as a paucity of clinical trials, create challenges in the diagnosis and management of pediatric arterial ischemic stroke (AIS). The neurological presentation of AIS can be subtle. Radiographic diagnosis of acute AIS is also challenging because CT scan may be normal early on. Risk factors include vascular, intravascular, and embolic disorders; frequently, there are multiple risk factors in a given child, necessitating thorough investigations. More than 50% have a vasculopathy including postvaricella angiopathy, dissection, moyamoya, or vasculitis. Intravascular mechanisms are frequently present, including dehydration. Hematological or prothrombotic conditions are also associated with AIS in children, and include sickle cell disease and prothrombotic disorders. The latter have been identified in from one third to one half of children with AIS, are usually acquired, and frequently act in concert with other risk factors for stroke. The most common embolic source is congenital heart disease, which is present in 25% of children with AIS. Outcomes include death in 6% and neurological deficits in two thirds of children. Given that no clinical trials have been completed in pediatric stroke to date, treatment is empiric. Initial neuroprotective strategies aim to reduce the size of the infarct. For older children antithrombotic agents (antiplatelet drugs and anticoagulants) are given to reduce the 20 to 30% risk of recurrence. There are coordinated research efforts currently being initiated, which over the next decade will result in clinical trials in this understudied condition.     

Reducing hospitalizations and arrests for substance abusers

This four-year outcome study examines the results of the VA Contracted Residential Substance Abuse Treatment for veterans with substance abuse problems. Race, marital status, housing status, and exposure to combat in the military characterized the male veteran subjects. Hospitalization rates and arrest rates were tracked for two years prior to and two years post-residential treatment. The authors also examined treatment outcomes for those who completed outpatient substance abuse treatment after an episode of residential care. This study shows a 30% reduction of hospitalizations and arrests following residential treatment. Those veterans who completed both residential and outpatient treatment had the best outcomes in terms of number of hospitalizations and arrests in a two-year follow-up.