In vitro and in vivo selectin-blocking activities of sulfated lipids and sulfated sialyl compounds

There is accumulating evidence that sulfated lipids, sulfated oligosaccharides and other sulfated compounds are reactive with selectins in a manner that interferes with selectin interactions with their natural ligands. In the report we describe the ability of sulfated lipids (sulfatides and gangliosides) and multimeric forms of sulfated sialic acid to block binding of P- and E-selectin-Ig to neutrophils. The in vivo ability of these compounds to block lung injury in rats following i.v. infusion of purified cobra venom factor (CVF), which induces injury that is L- and P-selectin dependent, was also determined as well as effects on recruitment of neutrophils, as measured by lung myeloperoxidase. There was a significant correlation between the ability of sulfated lipids and sialyl compounds to interfere in vitro with P-selectin-Ig binding to neutrophils and to protect against P-selectin-dependent acute lung injury induced by CVF. The biological effects of these sulfated compounds were also associated with diminished accumulation of neutrophils. The protective effects of these compounds may be linked to their ability to interfere with P- selectin binding to counter-receptors on neutrophils.      

Cystic fibrosis and the phenotypic expression of autosomal dominant polycystic kidney disease

Recent experiments in cultured cyst epithelial cells from kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) have shown that the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is present in the apical surface of these cells and mediates chloride (Cl-) and fluid secretion in vitro. To determine whether the presence of CF with the expression of mutated CFTR proteins modifies cyst formation in ADPKD, we studied a large family with both inherited diseases. ADPKD in this family is linked to PKD1. The family is composed of 26 members; 11 members with ADPKD, 4 members with CF, and 2 members with both diseases. Renal volumes measured by computerized tomography (CT), calculated creatinine clearances, and other clinical parameters in the family members with ADPKD and CF were compared with those in the family members with ADPKD alone, as well as to a large population of patients with ADPKD. The patients with CF and ADPKD, but not the CF heterozygote carriers with ADPKD, had less severe polycystic kidney and liver disease, as indicated by normal renal function; smaller renal volume, even when corrected for height and body surface area; and the absence of hypertension and liver cysts. These observations suggest that the coexistence of CF may reduce the severity of ADPKD.     

Sexual victimization in adolescent girls (age 15–20 years) enrolled in post-mandatory schools or professional training programmes in Switzerland

An analysis of data from the Swiss Multicenter Adolescent Survey on Health was conducted to assess the prevalence of a history of sexual victimization among a national sample of adolescent girls enrolled in schools or professional training, to estimate the number of associated psychosocial health problems, and to gain information on the effects of disclosure of the experience. A representative sample of 9268 adolescents answered a written questionnaire on health and lifestyle. Of the 3993 participating girls, 18.6% reported an experience of sexual victimization. The burden of associated psychosocial health problems was considerable, notably as regards depression, suicidal behaviour and substance misuse. Preliminary findings on the relation of disclosure and mechanisms of learned helplessness stress the need for more research on this issue. The results stress the importance of prevention programmes for adolescents and preadolescents, of physicians' awareness and training for screening and appropriate counselling, and of easy access to professional support.     

Impact of a modified directly administered antiretroviral treatment intervention on virological outcome in HIV-infected patients treated in Burkina Faso and Mali

Objective

This study explores whether viral load measurements can be used in resource‐limited settings to target those in need of adherence assistance. It was hypothesized that high plasma viral loads (pVLs) (≥500 HIV‐1 RNA copies/mL) were the result of poor antiretroviral therapy adherence and amenable to improvement with adherence assistance.

Design

A single‐arm, multicentre pilot study was conducted from November 2003 to March 2004 on 606 treatment‐experienced patients who had initiated an antiretroviral regimen in Mali and Burkina Faso ≥6 months before study enrolment. In these patients, those whose pVL was ≥500 copies/mL were offered 1 month of modified directly administered antiretroviral treatment (mDAART) with weekly follow‐up visits from pharmacists or adherence counsellors.

Methods

An adherence questionnaire was given to all cohort patients and viral load was used to screen for patients with ≥500 copies/mL. mDAART participants included cohort patients with ≥500 copies/mL, who completed the adherence questionnaire. Genotypic analyses were conducted on samples taken prior to and after the intervention. The intervention was considered effective when there was a decrease of ≥1 log₁₀ in pVL.

Results

mDAART was effective in over one‐third of the intervention participants, while in two‐thirds no decrease in pVL was observed. The majority of mDAART participants had major resistance mutations.

Conclusions

pVL measurement was useful to identify patients who needed adherence assistance. However, because it was performed ≥6 months after starting treatment, mDAART came too late for most participants, as they had already developed important resistance mutations that might have been avoided with better laboratory monitoring.     

Clinical outcomes and maternal perceptions of an updated model of perinatal care

BACKGROUND: Postpartum hospital stays seem likely to remain limited even under new laws which mandate that insurers cover 48-hour hospitalization after uncomplicated delivery. Clinicians, who are increasingly practicing in capitated arrangements, need better information to maximize clinical benefit to mothers and newborns using finite resources. OBJECTIVE AND INTERVENTIONS: This study's aim was to evaluate the clinical outcomes, patient perceptions, and costs of a revised model of perinatal care services. In this model, a new postpartum care center was established for routine follow-up of newborns within 48 hours after hospital discharge, educational efforts were shifted from the postpartum hospitalization to the prenatal period, and lactation consultant hours were increased. DESIGN AND PARTICIPANTS: Controlled, nonrandomized (double cohort) study that compared mothers and newborns with hospital stays of 48 hours or less during the Baseline Care (preintervention) study period (N = 344) with those under the Revised Care (postintervention) study period (N = 456). SETTING: The Hayward, California, medical center of Kaiser Permanente, a nonprofit health maintenance organization. DATA COLLECTION: Telephone interviews were attempted with all mothers 3 weeks after delivery. Data on rehospitalizations, emergency department (ED) and clinic visits, and costs during the first 14 postpartum days were collected from computerized databases and chart review. OUTCOME MEASURES: The combined clinical outcome was defined as any undesirable health event, including rehospitalization, an ED visit, or an urgent clinic visit by either the mother or newborn within the first 14 days postpartum, or breastfeeding discontinuation within the first 21 days postpartum. Maternal satisfaction and costs were also studied. RESULTS: Of 876 attempted interviews, 800 were completed (91%). Analyses were adjusted for age, race, education, parity, breastfeeding experience, and other relevant variables. Among the interviewed mother-newborn pairs, 45% in the Revised Care group experienced the combined clinical outcome, compared with 52% in the Baseline Care group. Newborns in the Revised Care group (29%) were significantly less likely to make urgent clinic visits during the first 14 days of life than those in the Baseline Care group (36%). There were no differences between groups in newborn ED visits or rehospitalizations, maternal clinical outcomes, or breastfeeding continuation. Mothers in the Revised Care group expressed higher satisfaction with the newborn's care, the amount of information they received about newborn care and breastfeeding, and the amount of help they received with breastfeeding. Planned hospital care, planned follow-up visits, and unplanned care costs decreased by $149 per delivery, while the new prenatal class and increased lactation consultant services cost $58 per delivery, for an estimated overall reduction in cost. CONCLUSIONS: We conclude that the revised model of perinatal care in this health maintenance organization medical center improved clinical outcomes and maternal satisfaction for low-risk mothers and newborns without increasing costs.