Gender Differences in Relative Dilatation of Abdominal Aortic Aneurysms

It has been postulated that gender differences in abdominal aortic aneurysm (AAA) rupture risk are due to variation in proportional dilatation. This study’s purpose was to examine differences in relative dilatation of AAAs as related to rupture risk and repair thresholds. During a recent 20-month period (August 2003-March 2005), all patients receiving elective endovascular repair of an AAA underwent computer-generated computed tomographic measurements, including suprarenal aortic diameter (D1) and maximum aneurysm diameter (D3). As a measure of proportional dilatation, a D3/D1 ratio was calculated for each patient and compared between genders. Values for males and females were plotted separately (D3 vs. D3/D1), and the resulting linear regression equations allowed for the comparison of proportional dilatation of aneurysms between genders. In 129 patients (108 males, 21 females), mean D3 did not differ between genders (62 ± 9.0 vs 63.4 ± 10.8 mm, p = 0.89), while relative dilatation (D3/D1) was significantly greater in females compared to males (2.82 ± 0.52 vs. 2.55 ± 0.42, p = 0.02). Linear regression analysis allowed for comparison of D3 as a function of D3/D1 and correlated a 55 mm AAA in males with one of 52 mm in females. These differences became greater with increasing AAA diameters (e.g., 60 and 70 mm AAAs in a male were proportionally similar to 56 and 62 mm AAAs in a female). AAAs of equal diameter represent a greater proportional dilatation in females than in males. This supports the recommendation for a smaller aneurysm diameter (52 mm) threshold for repair in females rather than the commonly used 55 mm threshold in males. Also, these data suggest that the gender difference in rupture risk widens exponentially as aneurysm diameter, and thereby proportional dilatation, increases above this repair threshold.     

Examination of the Trend in Canada Toward Geographic Centralization of Aneurysm Surgery during the Endovascular Era

Unlike in the United States, endovascular aneurysm repair (EVAR) has not been widely disseminated in Canada but has remained limited to large-volume vascular surgery units. Since the development of the endovascular program at our hospital, we have experienced a growth in our aneurysm practice and the area of referral. The purpose of this study was to compare the geographic referral area of our aneurysm practice between 1997 (prior to the introduction of EVAR) and 2003 (EVAR and open surgery). Our prospective database was reviewed to identify patients who underwent elective open aneurysm repair in 1997 and 2003 and those who underwent EVAR in 2003. Each patient’s county of residence was identified, allowing for grouping of patients into one of four geographic regions (I-IV) increasingly more distant from our hospital. Proportions were compared with the χ² test. In 1997, 105 patients underwent open abdominal aortic aneurysm repair, with the majority of patients originating from the two regions in closest proximity to our hospital (I, 34%; II, 46%; III, 18%; IV, 2%). This contrasts with the 2003 EVAR group (n = 63), which had a higher proportion of patients referred from greater distances (I, 13%; II, 27%; III, 27%; IV, 33%) (p < 0.001). The 2003 open group (n = 165) did not differ statistically with respect to region of origin (I, 18%; II, 41%; III, 21%; IV, 19%) compared to their 2003 EVAR counterparts (p = 0.075) but did have a higher proportion of patients from the more distant regions compared to the 1997 open group (p < 0.001). During the last 5 years, we have experienced a doubling of our elective aneurysm case volumes as well as a trend for patients to be referred from greater distances for both EVAR and open repair. This suggests a trend in Canada toward increased centralization of aneurysm care in centers providing both endovascular and open surgical alternatives. Presented at the Twenty-sixth Annual Meeting of the Canadian Society for Vascular Surgery, Quebec City, Canada, October 22-23, 2004.     

Is mixed‐handedness a marker of treatment response in posttraumatic stress disorder?: A pilot study

Recent studies suggest that mixed-handedness is a risk factor for posttraumatic stress disorder (PTSD). This study examined whether mixed-handed veterans with combat-related PTSD respond more poorly to psychosocial treatment. Consistency of hand preference was assessed in 150 Vietnam combat veterans with PTSD using the Edinburgh Handedness Inventory (R. C. Oldfield, 1971). Growth modeling analyses using Mplus (L. K. Muthén & B. Muthén, 2002) identified that PTSD veterans with mixed-handedness reported significantly less treatment improvement on the PTSD Checklist (F. W. Weathers, B. T. Litz, D. S. Herman, J. A. Huska, & T. M. Keane, 1993) than did veterans with consistent handedness. These data suggest that mixed-handedness is associated with poorer PTSD treatment response. Several possible explanations for this finding are discussed.     

Influence of biotransformation on trophic transfer of the PAH, fluoranthene

The persistence of polycyclic aromatic hydrocarbons (PAHs) in marine sediments may be influenced by benthic invertebrate bioturbation. Through processes such as deposit-feeding and enhancement of microbial metabolic activity PAHs may be remobilized from the sediment compartment, and either transferred to organisms at higher trophic levels or to the overlying water column, both processes inevitably changing the bioavailability of the PAH. Accumulation of contaminants from one level in the food chain to the next depends on feeding rate and assimilation efficiency, two factors that basically vary with food quality and contaminant type. Though it is generally believed that pre-consumptive biotransformation will reduce bioavailability due to the more polar nature of the metabolites compared to the unchanged parent compound, theoretically the decrease in lipophilicity will increase the sediment/food desorption rate in the intestine, and some metabolites will still be lipophilic enough to be absorbed by passive diffusion. We examined the trophic transfer of the PAH, fluoranthene from two closely related polychaete species (i.e., Capitella sp. I and Capitella sp. S), differing in their biotransformation ability, to the predatory polychaete, Nereis virens. We found that N. virens fed the biotransforming species, Capitella sp. I, accumulated significantly more Flu equivalents compared to worms fed Capitella sp. S, which have a very limited biotransformation ability. The dose-specific increase in N. virens intestinal Flu concentration was approximately twice as high in worms fed Capitella sp. I (equation: gut content=7.3 x dose-3.9) compared to worms fed Capitella sp. S (equation: gut content=3.2 x dose+0.6). In addition, we measured DNA damage, using the comet assay, in N. virens intestinal cells after feeding with the two prey species. We did not detect DNA damage above 'background' levels for worms fed either of the two Capitella species, possibly due to relatively low intestinal Flu concentrations in N. virens. Our results indicate that accumulation of PAHs by infaunal organisms may play an important role in the transfer of this type of contaminant to higher trophic levels. Moreover, we observed differences in transfer potential between parent compounds and their respective metabolites, which may influence the fate of these compounds in marine ecosystems. However, from the present study it cannot be concluded whether differences in biotransformation ability among prey species can lead to different effects in their predators.     

Transesterification of p-hydroxybenzoate esters (parabens) by human intestinal (Caco-2) cells

p-Hydroxybenzoate ester (paraben) preservatives are used in numerous orally administered products. The recognized route of metabolism for parabens is hydrolysis to p-hydroxybenzoic acid followed by conjugation and excretion. However, in the presence of alcohols, a presystemic transesterification pathway not previously reported for the human intestine can occur. Using human intestinal (Caco-2) cells, it was observed that hydrolysis of parabens to p-hydroxybenzoic acid is reduced markedly by ethanol concentrations that can occur in the human intestine, 0.25-0.5% (v/v). Ethanol concentrations of 1.0-2.5% (v/v) were optimal for transesterification to ethylparaben in Caco-2 cell homogenates. The kinetics of the transesterification reaction with regard to ethanol concentration (0-20%), time, pH (3-9), protein concentration (1-5 mg ml-1) and substrate concentration (6.25-200 microM) as well as the effects of different alcohols were studied. The Km and Vmax values for transesterification with ethanol for methyl, propyl, butyl, heptyl and octyl parabens were 449.7, 165.7, 86.1, 24.2 and 45.9 microM and 114.4, 37.5, 19.5, 7.5 and 7.6 micromol h-1 mg-1 Caco-2 cell protein, respectively. The Vmax values for transesterification of methylparaben with ethanol, propan-1-ol, butan-1-ol were 114.4, 5.1 and 4.9 micromol h-1 mg-1, respectively. Collectively, the kinetic data demonstrate that the enzyme responsible for the transesterification reaction has a preference for short-chain esters and represents the first report of transesterification in human intestinal cells. An implication of this mechanism is that alcohol-containing in vitro biosystems or protocols for the study of parabens disposition could generate transesterified artefacts. The clinical or toxicological implication is that, following co-ingestion of ester compounds with ethanol, transesterification could provide the basis for a previously unrecognized drug-alcohol interaction.     

Acculturation and eating disorders in Asian and Caucasian Australian university students

This study aimed to compare the attitudes and psychopathology of eating disorders of Asian and Caucasian university students using a survey method. The study also investigated the relationship between acculturation, attitudes and psychopathology of eating disorders in sub-groups of Asian girls. There were 130 Asian and 110 Caucasian adolescent girls, aged 18-24 who were screened using the Eating Attitudes Test (EAT-26), the Eating Disorders Inventory (EDI-2) and an Acculturation Index. The Asian group did not have higher mean EAT score than the Caucasian group, but had higher mean score in some sub-scales of the EDI-2. Eating disordered attitudes and psychopathology was not significantly different in the low compared to the high accultured Asian girls. This study suggests that Asian and Caucasian university students in Western Australia are equally susceptible to eating disorders, and that the level of acculturation does not modify the susceptibility of Asian students for eating disorders.     

Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review

OBJECTIVES: To determine whether any particular intervention or combination of interventions is effective in the treatment, management and rehabilitation of adults and children with a diagnosis of chronic fatigue syndrome / myalgic encephalomyelitis (CFS/ME). DESIGN: Substantive update of a systematic review published in 2002. Randomized (RCTs) and non-randomized controlled trials of any intervention or combination of interventions were eligible for inclusion. Study participants could be adults or children with a diagnosis of CFS/ME based on any criteria. We searched eleven electronic databases, reference lists of articles and reviews, and textbooks on CFS/ME. Additional references were sought by contact with experts. RESULTS: Seventy studies met the inclusion criteria. Studies on behavioural, immunological, pharmacological and complementary therapies, nutritional supplements and miscellaneous other interventions were identified. Graded exercise therapy and cognitive behaviour therapy appeared to reduce symptoms and improve function based on evidence from RCTs. For most other interventions, evidence of effectiveness was inconclusive and some interventions were associated with significant adverse effects. CONCLUSIONS: Over the last five years, there has been a marked increase in the size and quality of the evidence base on interventions for CFS/ME. Some behavioural interventions have shown promising results in reducing the symptoms of CFS/ME and improving physical functioning. There is a need for research to define the characteristics of patients who would benefit from specific interventions and to develop clinically relevant objective outcome measures.     

Safety and immunogenicity of an oral, inactivated, whole-cell vaccine for Shigella sonnei: preclinical studies and a Phase I trial

Orally delivered, inactivated whole-cell vaccines are safe methods of inducing local and systemic immunity. To increase surface proteins associated with adherence and invasion, Shigella sonnei were grown in BHI broth containing deoxycholate. A whole-cell vaccine (SsWC) was then produced by formalin inactivation. In pre-clinical studies, the SsWC vaccine was immunogenic and protected against S. sonnei-induced keratoconjunctivitis in the guinea pig model. In a randomized, double-blind, placebo-controlled, Phase I study, 10 evaluable subjects received either three doses of SsWC on Days 0, 14, and 28 (N = 3); five doses of SsWC on Days 0, 2, 4, 6, and 28 (N = 4); or placebo (N = 3). Each dose contained 2.0 x 10(10) inactivated cells. Serum and fecal antibodies against SsWC, LPS, and IpaC were measured by ELISA. A > or = 4-fold increase in titer was considered significant. Both SsWC dosing regimens were well tolerated. No fever or severe gastrointestinal symptoms were noted by any of the vaccinated subjects. Antibody responses were similar in the two dosing groups. Serum IgG or IgA responses to SsWC were seen in six of seven vaccinees (86%), to LPS in four of seven (57%), and to IpaC in five of seven (61%). Fecal IgA responses to these three antigens developed in five of five, three of five, and three of five subjects, respectively. Among the seven vaccinees, geometric mean rises in serum IgA levels to all three immunogens were significant; IgG increases trended toward significance (paired one-tailed t-test). We conclude that SsWC was immunogenic and protective in animal studies and well tolerated and immunogenic in a Phase I trial.