Echocardiographic characteristics including tissue Doppler imaging after enhanced external counterpulsation therapy

This study assessed the effects of a course of enhanced external counterpulsation (EECP) therapy on systolic and diastolic cardiac function using echocardiography to measure left ventricular ejection fraction (LVEF), end-systolic volume (ESV), end-diastolic volume (EDV), systolic wave (Sm), early diastolic wave (Ea), Vp, E/Ea, E/Vp, and diastolic function grade in 25 patients before and after 35 hours of EECP. EECP reduced ESV and EDV and increased ejection fraction significantly in patients with baseline LVEF < or = 50% (P=.018, .013, .002), baseline E/Ea > or = 14 (P=.032, .038, .007), baseline grade II or III diastolic dysfunction (decreased compliance) (P=.014, .032, .027), baseline Ea <7 cm/s (P=.015, .024, .001), and baseline Sm <7 cm/s (P=.017, .016, .006), but not in patients with baseline LVEF >50%, baseline E/Ea <14, baseline normal diastolic function or grade I diastolic dysfunction (impaired relaxation), baseline Ea > or = 7 cm/s, and Sm > or = 7 cm/s. These results demonstrate improved systolic and diastolic function in selected patients and provide new insight into potential clinical applications of EECP.     

Neuropsychological deficits in human immunodeficiency virus type 1 clade C-seropositive adults from South India

Most studies of cognitive functioning in human immunodeficiency virus type 1 (HIV-1)-seropositive (HIV-1+) subjects have been done in the United States and Europe, where clade B infections predominate. However, in other parts of the world such as South India, where clade C HIV is most common, the prevalence of HIV-1 is increasing. Standardized neuropsychological tests were used to assess cognitive functioning in a sample of 119 adults infected with clade C HIV-1 who were not on antiretroviral medications. The subjects did not have neurological or psychiatric illness and were functioning adequately. Neuropsychological test performance was compared with gender-, age-, and education-matched normative data derived from a sample of 540 healthy volunteers and a matched cohort of 126 healthy, HIV-1-seronegative individuals. Among the seropositive subjects, 60.5% had mild to moderate cognitive deficits characterized by deficits in the domains of fluency, working memory, and learning and memory. None of the subjects had severe cognitive deficits. The HIV-1+ sample was classified into groups according to the level of immune suppression as defined by CD4 count (<200, 201–499, and >500 cells/mm³) and viral load (<5000, 5001–30,000, 30,001–99,999, 100,000–1,000,000, and >1,000,001 copies). Although the most immunosuppressed group (CD4 count <200 cells/mm³ or viral load >1,000,001 copies) was small, their rate of impairment in visual working memory was greater when compared to groups with better immune functioning. Mild to moderate cognitive deficits can be identified on standardized neuropsychological tests in clade C-infected HIV-1+ adults who do not have any clinically identifiable functional impairment. The prevalence of cognitive deficits is similar to that reported in antiretroviral treatment-naïve individuals infected with clade B virus in the western world.     

What are the effects of providing evidence‐based information on eating disorders and their treatments? A randomized controlled trial in a symptomatic community sample

Aim: We hypothesize that a reason for the infrequent uptake of treatments by people with eating disorders is poor knowledge about treatments and outcomes for eating disorders (ED‐Mental Health Literacy; ED‐MHL). Our aim was to test putative health benefits of a brief ED‐MHL intervention. Methods: In a community‐based two‐phase survey, 122 young women (mean age 28.5 SD 6.3 years) with ED symptoms meeting DSM‐IV criteria for clinical severity were randomized to receive either a brief ED‐MHL intervention (comprising information about efficacious treatments, reputable self‐help books and where to go for further information and/or services) or information about local mental health services only. All were given feedback on their scores on measures of ED symptoms and quality of life. ED‐MHL, ED symptoms and health‐related quality of life were assessed prior to the intervention and at 6‐ and 12‐month follow‐up. Results: One hundred and two participants (84%) completed follow‐up at 12 months. Symptomatic improvement and changes in specific aspects of ED‐MHL, namely, less pessimism about how difficult EDs are to treat and improved recognition and knowledge, as well as increased help seeking, were observed in both groups. Differences between groups were uncommon but compared with control participants, those in the intervention group had improved health‐related quality of life. Conclusions: A brief community‐based intervention aimed to improve knowledge and beliefs about EDs and their treatments may be a valuable first step in improving health‐related outcomes for people with ED, but more research is needed.     

Radiology-Pathology Conference: choledochal cyst

We report the radiologic and pathologic findings of a newborn with a choledochal cyst and review the etiology, diagnostic considerations, and management of this entity.     

Radiation Induced Oral Mucositis

Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i) With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii) who also received concomitant chemotherapy; (iii) who received a total dose over 5,000 cGy; and (iv) who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene     

Proteomic Identification of OprL as a Seromarker for Initial Diagnosis of Pseudomonas aeruginosa Infection of Patients with Cystic Fibrosis

Identification of new immunogenic antigens that diagnose initial Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) alone or as an adjunct to microbiology is needed. In the present study, a proteomic analysis was performed to obtain a global assessment of the host immune response during the initial P. aeruginosa infection of patients with CF. Matrix-assisted laser desorption ionization-time of flight mass spectrometry was used to identify outer membrane protein L (OprL), a non-type III secretion system (TTSS) protein, as an early immunogenic protein during the initial P. aeruginosa infection of patients with CF. Longitudinal Western blot analysis of sera from 12 of 14 patients with CF detected antibodies to OprL during the initial P. aeruginosa infection. In addition, also detected were antibodies to ExoS, ExoU, or ExoS and ExoU, the latter indicating sequential P. aeruginosa infections during initial infections. Detection of serum reactivity to OprL, along with proteins of the TTSS, and in conjunction with microbiology may diagnose initial P. aeruginosa infections in patients with CF.Cystic fibrosis (CF) is an autosomal recessive multisystem disease which is caused by mutations in the CF transmembrane conductance receptor. Patients with CF have chronic respiratory infections which are the primary cause of morbidity and premature mortality (16). Patients with CF are infected with bacterial pathogens on an age-dependent timeline (16). Typically, Staphylococcus aureus and nonencapsulated Haemophilus influenzae are the first isolates from infants with CF (34, 35). However, Pseudomonas aeruginosa infections in children with CF are associated with progressive lung disease (30, 33). Microbiology is used for the diagnosis of P. aeruginosa, but successful P. aeruginosa isolation can be complicated in nonexpectorating populations of infants and young children with CF (4). The diagnosis and eradication of the initial P. aeruginosa infection with antibiotics to prevent chronic infection and mucoid transformation are important, since this diagnosis influences the quality of life and long-term patient survival (1, 2, 7, 11, 29, 30). Non-culture-based tests, like serology, should assist microbiology in the early diagnosis of P. aeruginosa infection.P. aeruginosa serology continues to be challenging without defined commercially available antigens licensed in the United States that reflect the molecular pathogenesis of P. aeruginosa upon adaptation to the host environment (13). Høiby (24) and Döring and Høiby (10) have detected an antibody response against a pool of antigens from common P. aeruginosa serotypes. Elevating antibody titers against this pool of antigens correlated with worsening P. aeruginosa infections and a poor clinical prognosis. The clinical progression of CF lung disease may be a reflection of the molecular pathogenesis of P. aeruginosa. Recent studies have correlated serological reactivity and known P. aeruginosa virulence factors. West et al. (42) showed that during the initial P. aeruginosa infection of children with CF, detection of serum antibodies to exotoxin A (ETA) and a P. aeruginosa lysate occurred earlier than detection of serum antibodies to elastase or alkaline phosphatase; subsequently, Corech et al. (6) detected antibodies to components of the type III secretion system (TTSS) at a time similar to that of P. aeruginosa Sup and earlier than ETA, showing the potential of measuring the antibody response to components of the TTSS as an indication of initial infection with P. aeruginosa in children with CF. This also indicated a role for TTSS in the initial P. aeruginosa pathogenesis of the CF lung.In the present study, a proteomic analysis was performed to obtain a global assessment of the host immune response during the initial P. aeruginosa infection of patients with CF. The goal was to identify a cellular component of P. aeruginosa that elicits an early immune response to P. aeruginosa infection to provide a stable immunogenic indication of P. aeruginosa infection relative to P. aeruginosa virulence factors that may fluctuate in expression during the course of P. aeruginosa infection, especially following transition from the acute to the chronic infection phase (41). Outer membrane protein L (OprL), a non-TTSS protein, was identified as an early immunogenic protein in the initial P. aeruginosa infection of patients with CF.     

Motives for initiation,temporary discontinuation,and permanent discontinuation of hormone replacement therapy use among Norwegian women

Objective

The use of hormone replacement therapy (HRT) declined strongly in many countries after publication of the WHI-study. The purpose of the present study was to investigate HRT usage patterns and motives for initiation, temporary discontinuation, and permanent discontinuation of HRT use among Norwegian women.

Methods

A questionnaire study about use and attitudes towards HRT was carried out in 2005. Women 45–64 years old were invited to the study (n = 2325, response rate 47%).

Results

Women initiated HRT use mainly due to climacteric complaints (74%), while prophylactic motives were less frequently reported (27%). The most often reported benefits of HRT use were reduced climacterical symptoms, especially hot flushes/sweating (83%), and improved quality of life (59%). The major proportion of ever-users (57%) had at some point temporarily discontinued HRT use. The motive for temporary discontinuation of HRT use most frequently reported was to see if climacterical symptoms had ceased (58%). Permanent discontinuation of HRT use was most often motivated by anxiety to side effects (55%). In multivariable analyses, women using HRT prophylactically were less likely to temporarily discontinue use. Women with a positive attitude towards HRT were the most unlikely ones to permanently discontinue HRT use.

Conclusions

Temporary discontinuation of HRT use was common among Norwegian women. The majority of HRT users reported a reduction in climacteric complaints after initiation of HRT use but many women were afraid of side effects.     

Genomewide association study for onset age in Parkinson disease

Background

Signaling by the vitamin A-derived morphogen retinoic acid (RA) is required at multiple steps of cardiac development. Since conversion of retinaldehyde to RA by retinaldehyde dehydrogenase type II (ALDH1A2, a.k.a RALDH2) is critical for cardiac development, we screened patients with congenital heart disease (CHDs) for genetic variation at the ALDH1A2 locus.

Methods

One-hundred and thirty-three CHD patients were screened for genetic variation at the ALDH1A2 locus through bi-directional sequencing. In addition, six SNPs (rs2704188, rs1441815, rs3784259, rs1530293, rs1899430) at the same locus were studied using a TDT-based association approach in 101 CHD trios. Observed mutations were modeled through molecular mechanics (MM) simulations using the AMBER 9 package, Sander and Pmemd programs. Sequence conservation of observed mutations was evaluated through phylogenetic tree construction from ungapped alignments containing ALDH8 s, ALDH1Ls, ALDH1 s and ALDH2 s. Trees were generated by the Neighbor Joining method. Variations potentially affecting splicing mechanisms were cloned and functional assays were designed to test splicing alterations using the pSPL3 splicing assay.

Results

We describe in Tetralogy of Fallot (TOF) the mutations Ala151Ser and Ile157Thr that change non-polar to polar residues at exon 4. Exon 4 encodes part of the highly-conserved tetramerization domain, a structural motif required for ALDH oligomerization. Molecular mechanics simulation studies of the two mutations indicate that they hinder tetramerization. We determined that the SNP rs16939660, previously associated with spina bifida and observed in patients with TOF, does not affect splicing. Moreover, association studies performed with classical models and with the transmission disequilibrium test (TDT) design using single marker genotype, or haplotype information do not show differences between cases and controls.

Conclusion

In summary, our screen indicates that ALDH1A2 genetic variation is present in TOF patients, suggesting a possible causal role for this gene in rare cases of human CHD, but does not support the hypothesis that variation at the ALDH1A2 locus is a significant modifier of the risk for CHD in humans.