Asthma symptom perception and obesity in children

This study examined the relationship between obesity and asthma symptom perception in 200 youth with asthma. Repeated subjective and objective peak flow measurements were summarized using the Asthma Risk Grid (Klein et al., 2004), resulting in Accurate, Symptom Magnification and Danger Zone scores. Analyses were stratified by age and included ethnicity.For younger children, obesity was not significantly related to perception scores. For older children, a significant obesity-by-ethnicity interaction for Accurate Symptom Perception scores indicated that obese white children had lower accuracy than white nonobese children, while there was no difference for obese versus nonobese minority children. Obesity was also related to higher Symptom Magnification scores regardless of ethnicity for older children.These findings suggest that obesity may complicate asthma management by interfering with the ability to accurately perceive symptoms for some patients. More remains to be learned about the role of sociodemographic factors underlying this relationship.     

Structure-activity relationship of reversibly lipidized peptides: studies of fatty acid-desmopressin conjugates

Purpose. To synthesize a series of reversible fatty acid-desmopressin (DDAVP) conjugates and to study their structure-activity relationship as anti-diuretic drugs. Methods. Seven fatty acid conjugates of DDAVP were prepared using various reversible lipidization reagents as described in our previous reports. All products were purified by acid precipitation and/or size-exclusion chromatography. Reversed-phase HPLC was used to evaluate their purity and lipophilicity. The anti-diuretic efficacy of these fatty acid conjugates was assessed in vasopressin-deficient Brattleboro rats. Four selected conjugates, i.e., DPA, DPH, DPD and DPP (acetic, hexanoic, decanoic, and palmitic acid conjugate, respectively), along with DDAVP itself were used in Caco-2 cell uptake studies and their degradation and the regeneration of active DDAVP were investigated using an in vitro liver slice metabolic system coupled with a HPLC assay. Results. All fatty acid-DDAVP conjugates were more lipophilic than DDAVP as examined by HPLC analyses. When cysteine was used as the linker, the capacity index (k, a measure of lipophilicity) of the conjugates was linearly correlated with the number of carbons in the fatty acid chain. The anti-diuretic activity of the conjugates was correlated with the length of the fatty acid chain, with C10 as the minimal requirement for possessing the enhanced anti-diuretic activity. Among the seven fatty acid conjugates, palmitic acid conjugate was the most potent DDAVP derivative. Removal of carboxyl group from the cysteine linker completely abolished the enhancement of the activity. The extent of cellular uptake also positively correlated with the lipophilicity of the conjugates. The metabolism of DDAVP, DPH, DPD, and DPP by liver slices all followed first order kinetics with half-life of 0.30, 0.01, 0.06 and 3.44 hr, respectively. The degradation rates of DPH and DPD in the liver slice incubation were much faster than that of DDAVP and therefore an accumulation of regenerated DDAVP in the media was observed. In contrast, DPP was metabolized much slower than DDAVP and, consequently, no significant accumulation of regenerated DDAVP could be detected. Conclusion. Conjugation of DDAVP with fatty acids increased the lipophilicity and the anti-diuretic activity of this peptide drug. The anti-diuretic activity of lipidized DDAVP was dependent on the chain length of the fatty acid, as well as the structure of the linker in the conjugate. The preservation and enhancement of the in vivo anti-diuretic activity of the conjugates is most likely due to a combination of an improved pharmacokinetic behavior and a concurrent regeneration of active DDAVP in tissues.     

Effects of an extract of oystercatcher (Haematopus ostralegus) eggs from the Zeehavenkanaal in The Netherlands, and of its major contaminant, hexachlorobenzene, on the chicken embryo

Oystercatchers (Haematopus ostralegus) foraging on the canal 'Zeehavenkanaal' in the Netherlands have been shown to accumulate appreciable amounts of contaminants, especially hexachlorobenzene. The present study was performed to assess the embryotoxic effects of the present contaminants. To this end, a two step approach was followed. In step one, the toxic effects of hexachlorobenzene were studied in the chicken embryo bioassay, using concentrations realistic for the field situation. In step two, yolks of oystercatcher eggs were extracted and the embryotoxic potency of this extract was studied in the same bioassay, using doses of 1, 10 and 100% of the contaminant load in one average egg. The extract contained hexachlorobenzene and PCBs. However, presence of other compounds could not be excluded, since these were not analysed. Hexachlorobenzene induced a nonsignificant decrease in lymphocyte density in the bursa of Fabricius. The egg extract caused a 3.5 fold induction of EROD activity at the highest dose applied, and decreased lymphocyte density in the bursa of Fabricius.     

Basal norepinephrine in depersonalization disorder

In contrast to the noradrenergic dysregulation described in PTSD, little is known regarding noradrenergic function in dissociative disorders. The purpose of this preliminary study was to investigate basal norepinephrine in depersonalization disorder (DPD). Nine subjects with DSM-IV DPD, without lifetime PTSD, were compared to nine healthy comparison (HC) subjects. Norepinephrine was measured via 24-h urine collection and three serial plasma determinations. Groups did not differ significantly in plasma norepinephrine levels. Compared to the HC group, the DPD group demonstrated significantly higher urinary norepinephrine, only prior to covarying for anxiety. The DPD group also demonstrated a highly significant inverse correlation between urinary norepinephrine and depersonalization severity (r=-0.88). Norepinephrine and cortisol levels (reported in a prior study) were not intercorrelated. We concluded that although dissociation accompanied by anxiety was associated with heightened noradrenergic tone, there was a marked basal norepinephrine decline with increasing severity of dissociation. The findings are in concordance with the few reports on autonomic blunting in dissociation and merit further investigation.     

Contemporary treatment of heart failure: Is there adequate evidence to support a unique strategy for African-Americans? con position

Heart failure is a substantial cause of increased morbidity and mortality in the African-American population, with poorer prognosis versus white patients. Systolic heart failure is predominantly caused by poorly controlled hypertension in African-Americans. Overall, African-Americans remain underrepresented in morbidity and mortality heart failure trials, and further data are needed to confirm the potential benefit of present therapies and newer approaches to heart failure in African-Americans. Intensive blood pressure control and control of other risk factors, along with the appropriate application of evidence-based therapies including angiotensin converting enzyme (ACE) inhibitors and approved beta-blockers, are required to decrease racial disparities. Although some data suggest that contemporary treatment with ACE inhibitors and beta-blockers may be less effective in African-Americans in terms of reducing heart failure morbidity and mortality, there is not adequate evidence to support a unique strategy for this population. The use of evidence-based therapies should be equally applied to African-Americans as well as to other ethnic groups while awaiting further studies.     

Evaluating Function and Health Related Quality of Life in Patients Treated for Extremity Soft Tissue Sarcoma

Objective To evaluate how functional disability impacts on health related quality of life (HRQOL) of patients with extremity soft tissue sarcoma (STS) at 1 year post-surgery.Design and setting Survey of extremity STS patients pre-surgery and one-year post-treatment.Participants: 100 participants who were treated for extremity STS between 2001 and 2003 at four Canadian hospitals. Patients were over 16 years, non-metastatic at diagnosis, and had limb salvage surgery.Outcome measures Musculoskeletal Tumor Society Rating Scale (MSTS), a measure of impairment; Toronto Extremity Salvage Score (TESS), a measure of activity limitations; Reintegration to Normal Living Index (RNL), a measure of participation restrictions; and EQ-VAS, a measure of HRQOL.Results After adjusting for demographic and clinical variables, impairment explained 54%, activity limitations explained 48%, and participation restrictions explained 61% of the variation in HRQOL. After adjustment, when all three functional measures were included in the model, only participation restrictions had a significant impact on HRQOL explaining 63% of the variation.Conclusion Impairment and activity limitations affect the daily activities a patient can perform, but it is the restriction in participation of life roles and situations that has the greatest effect on patient’s HRQOL.