Pseudoaneurysm: a complication of faulty technique in femoral arterial puncture

Pseudoaneurysm is a well-documented but rare complication of retrograde femoral arterial puncture. We present six patients in whom pseudoaneurysm complicated this procedure. The pseudoaneurysm arose from the superficial femoral artery in five patients and from the profunda femoris artery in one. An arteriovenous fistula also arose from the superficial femoral artery in one patient. In no patient did the pseudoaneurysm arise from the common femoral artery. Two mechanisms are postulated as to why pseudoaneurysms rarely complicate puncture of the common femoral artery.     

Self-efficacy as a predictor of treatment outcome in adolescent substance use disorders

Youth substance abuse relapse prevention was examined as a function of patients' situational self-efficacy (SE), their confidence to abstain from substance use in high-risk situations. An increase in SE has been shown to be enhanced by cognitive behavioral therapy (CBT) in adults. Eighty-eight adolescent substance abusers were randomly assigned to either CBT or psycho-education (PET) group therapy. Substance use and SE were assessed at end of treatment, 3- and 9-months after the end of planned treatment. Increased SE predicted subsequent abstinence independently from drug urinalysis and treatment condition only during treatment, while previous substance use predicted subsequent self-efficacy. CBT was not differentially effective than PET in promoting SE. It is recommended that potential mediators and moderators of SE in the treatment of adolescent substance abuse should be further explored.     

Inflammation associated with neoplastic colonic polyps

Little is known about the significance of inflammation in neoplastic colon polyps: tubular, tubulovillous, and villous polyps/adenomas (TVPs) and hyperplastic/serrated polyps (HSPs). We undertake this study to ascertain the significance of acute and chronic inflammation in neoplastic polyps. Eighty-one consecutive, randomized TVPs and fifty-four randomized HSPs accessioned in the UCHC surgical pathology laboratory were selected for final analysis. The TVPs display increased acute and chronic inflammation compared to normal and adjacent non-dysplastic colonic mucosa. Adenoma size correlates with degree of acute and chronic inflammation. TVPs show increased overall acute and chronic inflammation compared to HSPs of the same size. This difference was statistically highly significant (p<.001). The number of adenomas exhibiting high grade dysplasia was insufficient to evaluate the relationship between polyp inflammation, polyp size, and degree of dysplasia. The HSPs showed significantly lower incidence and severity of acute and chronic inflammation compared to the TVPs. No correlation was seen in the HSP group between polyp size and acute or chronic inflammation. The prevalence of IBD was higher in patients with HSP showing acute inflammation than in the general population, but this statistic may be skewed by the low overall incidence of acute inflammation in the HSP group.     

An interactive voice response (IVR) system for adolescents with alcohol use disorders: a pilot study

In order to understand predictors of relapse among adolescents treated for alcohol use disorders (AUD), it is important to accurately assess the daily circumstances associated with use. This pilot study investigates the feasibility and acceptability of an interactive voice response (IVR) system in adolescents with AOSUD. Twenty-six adolescents 14 to 19 years old, with a mean age of 16.8, who were enrolled into an adolescent treatment program for AUD consented to make phone calls for 14 successive evenings to an IVR system and answer 14 questions pertaining to daily use of alcohol and other drugs. The subjects were compensated for their participation. A satisfaction questionnaire was administered at the end of the study. Participants completed 72% of scheduled recordings, with an average of 10.1 calls per subject. Most participants reported that they answered the questions honestly and accurately and were very much satisfied with the IVR system. The preliminary data presented here suggests that the use of IVR for the purpose of generating daily reports in youth is feasible and acceptable. The utilization of IVR systems should be explored to improve efficacy and attainment of generalizability to heterogeneous adolescent populations and lifestyles including for other psychiatric disorders.     

Teenage pregnancy in type 1 diabetes mellitus

Carmody D, Doyle A, Firth RGR, Byrne MM, Daly S, Mc Auliffe F, Foley M, Coulter‐Smith S, Kinsley BT. Teenage pregnancy in type 1 diabetes mellitus Younger maternal age at delivery has been linked to adverse reproductive outcomes. Pregnancy complicated by type 1 diabetes mellitus (T1DM) is also associated with adverse pregnancy outcomes. Optimising diabetic glycaemic control prior to pregnancy is known to reduce the rate of congenital abnormalities and improve pregnancy outcomes. Teenage pregnancies are not usually planned and little data exist on teenage pregnancy complicated by T1DM. We sought to identify the glycemic control achieved in teenage pregnancy with T1DM and to clarify if there is an associated increase in adverse pregnancy outcomes compared to those seen in older women with T1DM. We compared outcomes in 18 teenagers (TG) with 582 older women with T1DM (CON) from 1995–2007. TG booked to the combined diabetes‐obstetrical service at a median gestational age of 11 weeks (range 6–22) compared to 7 weeks in CON (range 4–40, p < 0.02). Glycaemic was worse in TG compared to CON at 13, 26 and 35 weeks gestation, despite higher insulin doses. First trimester miscarriage rate did not differ between groups. Major congenital anomaly rate was 6.2% (1/16) compared to 3.2% in CON. This preliminary study has demonstrated that pregnant teenage women with T1DM book later to specialised care and have worse glycaemic control in pregnancy compared to older women with T1DM. This group also appear to be more insulin resistant than older women in early pregnancy. Our data would suggest that teenagers with type 1 diabetes mellitus may constitute a high‐risk group for adverse pregnancy outcomes.     

Myocardial deformation abnormalities in patients with aortic regurgitation: a strain rate imaging study

Aims: Early left ventricular (LV) dysfunction in asymptomatic patientswith severe aortic regurgitation (AR) may go undetected dueto the lack of a sufficiently sensitive diagnostic tool. Ultrasonicstrain/strain rate (S/SR) imaging should now provide such sensitivityin detecting early dysfunction in regional LV systolic deformation.The aim of this study was to understand and define the changesin LV regional systolic deformation based on S/SR imaging inpatients with asymptomatic or minimally symptomatic AR. Methods and results: Eighty-one individuals were studied: 59 asymptomatic patientswith isolated non-ischaemic AR who were divided into three sub-groupssuch as mild, moderate, and severe AR and 22 age-matched healthysubjects. All patients underwent standard echocardiographicexaminations including a tissue Doppler imaging study. For LVradial deformation, the posterior wall (LVPW) was examined.To assess LV longitudinal deformation, S and SR data were acquiredfrom the LV lateral wall and septum. Radial as well as longitudinalpeak systolic SRs were significantly decreased in patients withboth moderate AR (LVPW, P = 0.0009; septum, P = 0.03; LV lateralwall, P = 0.0009) and severe AR (P < 0.0001) compared withhealthy subjects. Changes in regional LV deformation correlatedinversely both with LV end-diastolic volume and with end-systolicvolume. Conclusions: Strain rate imaging is a sensitive tool in detecting the spectrumof changes in radial and longitudinal deformation in asymptomaticor minimally symptomatic patients with AR. The index where volumewas corrected by deformation should form the basis for predictingsubclinical LV dysfunction in patients with increasing LV dilatation.     

Testing human biologicals in animal host resistance models

The purpose of immunotoxicity testing is to obtain data that is meaningful for safety assessment. Host resistance assays are the best measure of a toxicant's effect on the overall ability to mount an effective immune response and protect the host from infectious disease. An outline is presented for immunotoxicological evaluation using host resistance assays. The influenza virus host resistance model is useful to evaluate the overall health of the immune system and is one of the most thoroughly characterized host resistance models. Viral clearance requires all aspects of the immune system to work together and is the ultimate measure of the health of the immune system in this model. Mechanistic immune functions may be included while measuring viral clearance and include: cytokines, macrophage activity, natural killer (NK) cell activity, cytotoxic T-lymphocyte (CTL) activity, and influenza-specific IgM and IgG. Measurement of these immunological functions provides an evaluation of innate immunity (macrophage or NK activity), an evaluation of cell-mediated immunity (CMI) (CTL activity), and an evaluation of humoral-mediated immunity (HMI) (influenza-specific IgM or IgG). Measurement of influenza-specific IgM or IgG also provides a measurement of T-dependent antibody response (TDAR) since influenza is a T-dependent antigen. There are several targeted host resistance models that may be used to answer specific questions. Should a defect in neutrophil and/or macrophage function be suspected, Streptococcus pneumoniae, Pseudomonas aeruginosa, or Listeria monocytogenes host resistance models are useful. Anti-inflammatory pharmaceuticals or therapeutics for rheumatoid arthritis or Crohn's disease that target TNFalpha may also be evaluated for immunotoxicity using the S. pneumoniae intranasal host resistance assay. Marginal zone B (MZB) cells are required for production of antibody to T-independent antigens such as the polysaccharide capsule of the encapsulated bacteria that are so prominent in causing blood-borne infections and pneumonia. Intravenous infection with Streptococcus pneumoniae, an encapsulated bacterium, results in a blood-borne infection that requires MZB cells for clearance. The systemic S. pneumoniae host resistance assay evaluates whether a therapeutic test article exerts immunotoxicity on MZB cells and measures the T-independent antibody response (TIAR). Suppression of CMI or in some cases HMI may result in reactivation of latent virus that may result in a fatal disease such as progressive multifocal leukoencephalopathy (PML). The murine cytomegalovirus (MCMV) reactivation model may be used to evaluate a pharmaceutical agent to determine if suppression of CMI or HMI results in reactivation of latent virus. Candida albicans is another host resistance model to test potential immunotoxicity. Host resistance assays have been the ultimate measure of immunotoxicity testing for environmental chemicals and pharmaceutical small molecules. Human biologicals are now an important component of the drug development armamentarium for biotech and pharmaceutical companies. Many human biologicals are fusions of IgG, and/or target immune mediators, immunological receptors, adhesion molecules, and/or are indicated for diseases that have immune components. It is therefore necessary to thoroughly evaluate human biological therapeutics for immunotoxicity. Numerous biologicals that are pharmacologically active in rodents can be evaluated using well-characterized rodent host resistance assays. However, biologicals not active in rodents may use surrogate biologicals for testing in rodent host resistance assays, or may use host resistance assays in genetically engineered mice that mimic the effect of the human biological pharmacological agent.     

Emotion in psychogenic nonepileptic seizures: responses to affective pictures

We examined emotional responses to standard affective pictures in 18 psychogenic nonepileptic seizure (PNES) patients. Given reports of trauma and posttraumatic stress symptoms (PTS) in many PNES patients, comparison groups were seizure-free individuals high and low in PTS (PTS-high, PTS-low; n=18 per group). Patients with psychogenic nonepileptic seizures (1) reported more emotional intensity to neutral and pleasant pictures than PTS-low and more intensity to neutral pictures than PTS-high, and (2) showed less positive emotional behavior to pleasant pictures than PTS-high. Groups did not differ in pleasantness/unpleasantness ratings, negative emotional behavior, cardiac interbeat interval, or respiratory sinus arrhythmia (RSA) reactivity to the pictures. Patients with psychogenic nonepileptic seizures reported more general emotion regulation difficulties and showed lower baseline RSA than PTS-low but not PTS-high. In sum, intense emotional experience and diminished positive emotional behavior characterized PNES patients' emotional responses.     

AZD1775 sensitizes T cell acute lymphoblastic leukemia cells to cytarabine by promoting apoptosis over DNA repair

While some children with acute lymphoblastic leukemia (ALL) have excellent prognoses, the prognosis for adults and children with T cell ALL is more guarded. Treatment for T-ALL is heavily dependent upon antimetabolite chemotherapeutics, including cytarabine. Targeted inhibition of WEE1 with AZD1775 has emerged as a strategy to sensitize cancer cells to cytarabine and other chemotherapeutics. We sought to determine if this strategy would be effective for T-ALL with clinically relevant anti-leukemia agents. We found that AZD1775 sensitizes T-ALL cells to several traditional anti-leukemia agents, acting synergistically with cytarabine by enhancing DNA damage and apoptosis. In addition to increased phosphorylation of H2AX at serine 139 (γH2AX), AZD1775 led to increased phosphorylation of H2AX at tyrosine 142, a signaling event associated with promotion of apoptosis over DNA repair. In a xenograft model of T-ALL, the addition of AZD1775 to cytarabine slowed leukemia progression and prolonged survival. Inhibition of WEE1 with AZD1775 sensitizes T-ALL to several anti-leukemia agents, particularly cytarabine. Mechanistically, AZD1775 promotes apoptosis over DNA repair in cells treated with cytarabine. These data support the development of clinical trials including AZD1775 in combination with conventional chemotherapy for acute leukemia.     

Effects of PCB (Aroclor 1254) on non-specific immune parameters in rhesus (Macaca mulatta) monkeys.

The effects of low level, chronic polychlorinated biphenyl--Aroclor 1254--(PCB) exposure were investigated on non-specific immune parameters in female rhesus (Macaca mulatta) monkeys. Five groups of monkeys were orally administered with PCB at concentrations of 0, 5, 20, 40 or 80 micrograms/kg bw/day. Immunotoxicity testing was initiated after 55 months of exposure. The serum hemolytic complement activity in all PCB treated groups was significantly higher (P less than 0.05) than that in the control group. A statistically significant dose-related increase in natural killer cell activity was evident at the 75:1 effector to target cell ratio. Similarly, a statistically significant dose-related increase was noted for thymosin alpha-1 levels but not for thymosin beta-4 levels. Statistically significant increased interferon levels were noted in the 20 and 80 micrograms/kg groups compared with the control group while the levels in the 40 micrograms/kg group were decreased significantly compared with the control group. The production of tumor necrosis factor by monocytes in the PCB treated groups was not different to that in the control group. The results indicated that long term exposure to PCB modulate several non-specific immune parameters.