Search

Irregular participation in HIV medical care hinders HIV RNA suppression and impacts health among people living with HIV. Cluster analysis of clinical data from 1,748 patients attending a large academic medical center yielded three HIV service usage patterns, namely: 'engaged in care', 'sporadic care', and 'frequent use'. Patients 'engaged in care' exhibited most consistent retention (on average, >88 % of each patient's observation years had ≥2 visits 90 days apart), annualized visit use (2.9 mean visits/year) and viral suppression (>73 % HIV RNA tests <400 c/mL). Patients in 'sporadic care' demonstrated lower retention (46-52 %), visit use (1.7 visits/year) and viral suppression (56 % <400 c/mL). Patients with 'frequent use' (5.2 visits/year) had more inpatient and emergency visits. Female, out-of-state residence, low attendance during the first observation year and detectable first-observed HIV RNA were early predictors of subsequent service usage. Patients 'engaged in care' were more likely to have HIV RNA <400 than those receiving sporadic care. Results confirm earlier findings that under-utilization of services predicts poorer viral suppression and health outcomes and support recommendations for 2-3 visits/year.

Background: There have been few studies on muscle injury caused by cytotoxic agents used in cancer. In particular, only four cases of muscle manifestations have been reported in patients who received gemcitabine as single chemotherapy without adjuvant radiotherapy. In only one of these observations gemcitabine was considered to be the causative agent., Methods: We report the case of a patient without comorbidity treated with gemcitabine monotherapy for 2 months for pancreatic adenocarcinoma, who developed a proximal motor deficiency of the lower limbs and myolysis (creatinine kinase 1858 IU/L) associated with an erythema of both thighs., Results: Muscle MRI revealed the presence of edema on both the quadriceps muscles. A muscle biopsy showed post-necrotic regeneration and significant vascular proliferation. Only three small inflammatory infiltrates were observed, while expression of the major histocompatibility complex class I in muscle fibers was normal. There was no recurrence of cancer, anti-TIF-1γ antibodies tested negative, and discontinuation of gemcitabine, without further treatment, resulted in complete disappearance of symptoms., Conclusions: The present observation suggests that gemcitabine monotherapy without adjuvant radiotherapy can cause myopathy through vascular lesions, a mechanism which also underlies the more common side effects of this treatment. These findings have obvious therapeutic implications., (© 2013 Published by Elsevier Inc.)

Hepatitis E is a rare and usually asymptomatic infection. However, its incidence is rising in France, and it can cause severe or chronic manifestations in immunocompromised patients. Here, we report a case of hepatitis E in a patient with rheumatoid arthritis who had immunosuppression due to treatment with a biological agent., (Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Background: A growing corpus of research focuses on assessing the quality of the local built environment and also examining the relationship between the built environment and health outcomes and indicators in communities. However, there is a lack of research presenting a highly resolved, systematic, and comprehensive spatial approach to assessing the built environment over a large geographic extent. In this paper, we contribute to the built environment literature by describing a tool used to assess the residential built environment at the tax parcel-level, as well as a methodology for summarizing the data into meaningful indices for linkages with health data., Methods: A database containing residential built environment variables was constructed using the existing body of literature, as well as input from local community partners. During the summer of 2008, a team of trained assessors conducted an on-foot, curb-side assessment of approximately 17,000 tax parcels in Durham, North Carolina, evaluating the built environment on over 80 variables using handheld Global Positioning System (GPS) devices. The exercise was repeated again in the summer of 2011 over a larger geographic area that included roughly 30,700 tax parcels; summary data presented here are from the 2008 assessment., Results: Built environment data were combined with Durham crime data and tax assessor data in order to construct seven built environment indices. These indices were aggregated to US Census blocks, as well as to primary adjacency communities (PACs) and secondary adjacency communities (SACs) which better described the larger neighborhood context experienced by local residents. Results were disseminated to community members, public health professionals, and government officials., Conclusions: The assessment tool described is both easily-replicable and comprehensive in design. Furthermore, our construction of PACs and SACs introduces a novel concept to approximate varying scales of community and describe the built environment at those scales. Our collaboration with community partners at all stages of the tool development, data collection, and dissemination of results provides a model for engaging the community in an active research program.

Objectives: We examined whether the risk of premature mortality associated with living in socioeconomically deprived neighborhoods varies according to the health status of individuals., Methods: Community-dwelling adults (n = 566,402; age = 50-71 years) in 6 US states and 2 metropolitan areas participated in the ongoing prospective National Institutes of Health-AARP Diet and Health Study, which began in 1995. We used baseline data for 565,679 participants on health behaviors, self-rated health status, and medical history, collected by mailed questionnaires. Participants were linked to 2000 census data for an index of census tract socioeconomic deprivation. The main outcome was all-cause mortality ascertained through 2006., Results: In adjusted survival analyses of persons in good-to-excellent health at baseline, risk of mortality increased with increasing levels of census tract socioeconomic deprivation. Neighborhood socioeconomic mortality disparities among persons in fair-to-poor health were not statistically significant after adjustment for demographic characteristics, educational achievement, lifestyle, and medical conditions., Conclusions: Neighborhood socioeconomic inequalities lead to large disparities in risk of premature mortality among healthy US adults but not among those in poor health.

The aim of this study was to investigate the patterns of attendance at School Dental Service (SDS) and reasons for attendance (treatment or prevention) for children in the Perth Metropolitan Area, in particular investigating the first year of SDS attendance and attendance until the year the child turned 12. The first 150 SDS records located for children from the Western Australian Pregnancy Cohort (Raine) Study were used for this study. Patterns of attendance of children at SDS were described, as were associated factors (enrolment, age and nature of first visit, general nature of visits and number of visits) until the end of the year that the child turned 12.The age of the child at the first SDS visit ranged from 4 years 3 months to 14 years 11 months, with a median of 5 years 1 month. First visits were primarily for an examination (98%). Children had a median of 13 visits until 12 years of age, with 10% having less than five visits and 4% having more than 25 visits.These data provide useful information regarding attendance at the SDS in Western Australia which could provide a basis for oral health promotion programs.

The field of zoonoses changes constantly. Streptococcus equi subsp. ruminatorum is a group C Streptococcus subspecies first identified in 2004. The first case of human infection with this agent was reported in 2007. Here, we report a second case. A 70-year-old man had acute spondylodiscitis and endocarditis involving the anterior mitral valve leaflet. S. equi subsp. ruminatorum was identified in the blood cultures. Antibiotic therapy was successful in eradicating the infection. The workup showed hypogammaglobulinemia with stage I myeloma. He reported frequent contacts with horses including two that exhibited symptoms of upper airway infection a few days before his symptoms started. Serological tests indicated S. equi infection in both animals. This unusual case confirms that S. equi subsp. ruminatorum can cause human disease. In addition, our patient was probably contaminated via the skin, a mode of transmission that has not been described previously. It also highlights the usefulness of molecular biology tests, which should be performed routinely in patients with group C streptococcus infections and evidence suggesting a zoonosis., (Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Background: The care and protection of the estimated 143,000,000 orphaned and abandoned children (OAC) worldwide is of great importance to global policy makers and child service providers in low and middle income countries (LMICs), yet little is known about rates of child labour among OAC, what child and caregiver characteristics predict child engagement in work and labour, or when such work infers with schooling. This study examines rates and correlates of child labour among OAC and associations of child labour with schooling in a cohort of OAC in 5 LMICs., Methods: The Positive Outcomes for Orphans (POFO) study employed a two-stage random sampling survey methodology to identify 1480 single and double orphans and children abandoned by both parents ages 6-12 living in family settings in five LMICs: Cambodia, Ethiopia, India, Kenya, and Tanzania. Regression models examined child and caregiver associations with: any work versus no work; and with working <21, 21-27, and 28+ hours during the past week, and child labour (UNICEF definition)., Results: The majority of OAC (60.7%) engaged in work during the past week, and of those who worked, 17.8% (10.5% of the total sample) worked 28 or more hours. More than one-fifth (21.9%; 13% of the total sample) met UNICEF's child labour definition. Female OAC and those in good health had increased odds of working. OAC living in rural areas, lower household wealth and caregivers not earning an income were associated with increased child labour. Child labour, but not working fewer than 28 hours per week, was associated with decreased school attendance., Conclusions: One in seven OAC in this study were reported to be engaged in child labour. Policy makers and social service providers need to pay close attention to the demands being placed on female OAC, particularly in rural areas and poor households with limited income sources. Programs to promote OAC school attendance may need to focus on the needs of families as well as the OAC.

We report a case of a 72-year-old man who presented with bilateral panuveitis in a context of unclassified arthritis. The recurrence of uveitis associated with ear chondritis led to the diagnosis of relapsing polychondritis. Ocular symptoms are frequent in the course of relapsing polychondritis, but uveitis is a rare symptom and could compromise the visual outcome., (2010 Elsevier Masson SAS. All rights reserved.)

Objective: To determine the effects of reducing overnight basal insulin or a bedtime dose of terbutaline on nocturnal blood glucose (BG) nadir and hypoglycemia after exercise in children with type 1 diabetes mellitus., Study Design: Sixteen youth (mean age 13.3 years) on insulin pumps were studied overnight on 3 occasions after a 60-minute exercise session with BG measurements every 30 minutes. Admissions were randomized to bedtime treatment with oral terbutaline 2.5 mg, 20% basal rate insulin reduction for 6 hours, or no treatment., Results: Mean overnight nadir BG was 188 mg/dL after terbutaline and 172 mg/dL with basal rate reduction compared with 127 mg/dL on the control night (P = .002 and .042, respectively). Terbutaline eliminated nocturnal hypoglycemia but resulted in significantly more hyperglycemia (≥250 mg/dL) when compared with the control visit (P < .0001). The basal rate reduction resulted in fewer BG readings <80 and <70 mg/dL but more readings ≥250 mg/dL when compared with the control visit., Conclusions: A basal insulin rate reduction was safe and effective in raising post-exercise nocturnal BG nadir and in reducing hypoglycemia in children with type 1 diabetes mellitus. Although effective at preventing hypoglycemia, a 2.5-mg dose of terbutaline was associated with hyperglycemia., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Objective: This study determined the optimal timing of insulin bolus administration in relation to meal consumption in adolescents and adults with type 1 diabetes., Study Design and Methods: Twenty-three subjects participated in this crossover study consisting of three treatment arms: delivering an insulin glulisine bolus by insulin pump 20 min prior to a meal ("PRE"), immediately before the meal ("START"), and 20 min after meal initiation ("POST"). Blood glucose levels were measured every 30 min for a total of 240 min post-meal initiation. Mean blood glucose levels at 1 and 2 h after meal initiation, blood glucose area under the curve (AUC), and maximum blood glucose levels were analyzed., Results: At both 60 and 120 min after meal initiation, the PRE arm showed significantly lower glycemic excursions than the START arm (P = 0.0029 and 0.0294, respectively) and the POST arm (P = 0.001 and 0.0408, respectively). Glycemic AUC was significantly less in the PRE arm versus both the START and POST arms (159.5 +/- 58.9 mg/dL vs. 187.0 +/- 43.1 mg/dL [P = 0.0297] and 184.5 +/- 33.2 mg/dL [P = 0.0463], respectively). Peak blood glucose levels were significantly lower in the PRE arm compared to the START arm (P = 0.0039) and the POST arm (P = 0.0027)., Conclusions: A bolus of rapid-acting insulin 20 min prior to a meal results in significantly better postprandial glucose control than when the meal insulin bolus is given just prior to the meal or 20 min after meal initiation.

Background: Measures to assess neighborhood environments are needed to better understand the salient features that may enhance outdoor physical activities, such as walking and bicycling for transport or leisure. The purpose of this study was to derive constructs to describe neighborhoods using both primary (neighborhood audit) and secondary (geographic information systems) data., Methods: We collected detailed information on 10,770 road segments using an audit and secondary data. The road segment sample was randomly split into an exploratory (60%) and validation sample (40%) for cross-validation. Using the exploratory sample (n = 6,388), seven a priori constructs were assessed separately (functionality, safety, aesthetics, destinations, incivilities, territorality, social spaces) by urbanicity using multi-group confirmatory factor analysis (CFA). Additionally, new a posteriori constructs were derived using exploratory factor analysis (EFA). For cross-validation (n = 4,382), we tested factor loadings, thresholds, correlated errors, and correlations among a posteriori constructs between the two subsamples. Two-week test-retest reliability of the final constructs using a subsample of road segments (n = 464) was examined using Spearman correlation coefficients., Results: CFA indicated the a priori constructs did not hold in this geographic area, with the exception of physical incivilities. Therefore, we used EFA to derive a four-factor solution on the exploratory sample: arterial or thoroughfare, walkable neighborhood, physical incivilities, and decoration. Using CFA on the validation sample, the internal validity for these a posteriori constructs was high (range 0.43 to 0.73) and the fit was acceptable. Spearman correlations indicated the arterial or thoroughfare factor displayed near perfect reliability in both urban and rural segments (r = 0.96). Both the physical incivilities factor and the walkable neighborhood factor had substantial to near perfect reliability in both urban and rural segments (r = 0.77 to 0.78 and r = 0.79 to 0.82, respectively). The decoration factor displayed moderate reliability in urban segments (r = 0.50; 95% CI: 0.38-0.60) and lower reliability in rural segments (r = 0.39; 95% CI: 0.25-0.52)., Conclusion: The results of our analyses yielded four reliably and objectively measured constructs that will be used to explore associations with physical activity in urban and rural North Carolina. These constructs should be explored in other geographic areas to confirm their usefulness elsewhere.

Purpose: The purpose of this article is to describe the process of educating families and children with type 1 diabetes on real time continuous glucose monitoring (RT-CGM) and to note the similarities and differences of training patients using continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI)., Methods: A total of 30 CSII participants and 27 MDI participants were educated using the Navigator RT-CGM in a clinical trial. Time spent with families for visits and calls was tracked and compared between patient groups. The Diabetes Research in Children Network (DirecNet) educators were surveyed to assess the most crucial, time intensive, and difficult educational concepts related to CGM., Results: Of the 27 MDI families, an average of 9.6 hours was spent on protocol-prescribed visits and calls (not measured in CSII) and 2 hours on participant-initiated contacts over 3 months. MDI families required an average of 5.4 more phone contacts over 3 months than CSII families. According to the DirecNet educators, lag time and calibrations were the most crucial teaching concepts for successful RT-CGM use. The most time was spent on teaching technical aspects, troubleshooting, and insulin dosing. The most unanticipated difficulties were skin problems including irritation and the sensor not adhering well., Conclusion: Educators who teach RT-CGM should emphasize lag time and calibration techniques, technical device training, and sensor insertion. Follow-up focus should include insulin dosing adjustments and skin issues. The time and effort required to introduce RT-CGM provided an opportunity for the diabetes educators to reemphasize good diabetes care practices and promote self-awareness and autonomy to patients and families.

Introduction: In the present study, we investigated the ability of microparticles isolated from synovial fluids from patients with rheumatoid arthritis or osteoarthritis to induce the synthesis and release of key cytokines of B-lymphocyte modulation such as B cell-activating factor, thymic stroma lymphopoietin, and secretory leukocyte protease inhibitor by rheumatoid fibroblast-like synoviocytes., Methods: Microparticles were analyzed in synovial fluids from patients with rheumatoid arthritis, osteoarthritis, microcristalline arthritis, and reactive arthritis. In addition, microparticle release after activation from various cell lines (CEM lymphocyte and THP-1 cells) was assessed. Microparticles were isolated by differential centrifugation, and quantitative determinations were carried out by prothrombinase assay after capture on immobilized annexin V. B cell-activating factor, thymic stroma lymphopoietin, and secretory leukocyte protease inhibitor release was evaluated by enzyme-linked immunosorbent assay., Results: Microparticles isolated from synovial fluids obtained from rheumatoid arthritis and osteoarthritis patients or microparticles derived from activated THP-1 cells were able to induce B cell-activating factor, thymic stroma lymphopoietin, and secretory leukocyte protease inhibitor release by rheumatoid arthritis fibroblast-like synoviocytes. Conversely, CEM-lymphocytes-derived microparticles generated by treatment with a combination of PHA, PMA and Adt-D did not promote the release of B cell-activating factor but favored the secretion of thymic stroma lymphopoietin and secretory leukocyte protease inhibitor by rheumatoid arthritis fibrobast-like synoviocytes. However, microparticles isolated from actinomycin D-treated CEM lymphocytes were not able to induce B cell-activating factor, thymic stroma lymphopoietin, or secretory leukocyte protease inhibitor release, indicating that microparticles derived from apoptotic T cells do not function as effectors in B-cell activation., Conclusions: These results demonstrate that microparticles are signalling structures that may act as specific conveyors in the triggered induction and amplification of autoimmunity. This study also indicates that microparticles have differential effects in the crosstalk between B lymphocytes and target cells of autoimmunity regarding the parental cells from which they derive.

Healthy diet, physical activity, smoking, and adequate weight gain are all associated with maternal health and fetal growth during pregnancy. Neighborhood characteristics have been associated with poor maternal and child health outcomes, yet conceptualization of potential mechanisms are still needed. Unique information captured by neighborhood inventories, mostly conducted in northern US and Canadian urban areas, has been shown to reveal important aspects of the community environment that are not captured by the demographic quantities in census data. This study used data from the Pregnancy, Nutrition, and Infection (PIN) prospective cohort study to estimate the influences of individual-level and neighborhood-level characteristics on health behaviors and adequacy of weight gain during pregnancy. Women who participated in the PIN study and who resided in Raleigh, North Carolina and its surrounding suburbs were included (n = 703). Results from a neighborhood data collection inventory identified three social constructs, physical incivilities, territoriality, and social spaces, which were hypothesized to influence maternal health behaviors. The physical incivility scale was associated with decreased odds (adjusted OR = 0.74, 95%CI = 0.57, 0.98) in participating in vigorous leisure activity before pregnancy after controlling for several individual confounders, and a crude association for decreased odds of excessive weight gain (OR = 0.79, 95%CI = 0.64, 0.98). The social spaces scale was associated with decreased odds for inadequate (adjusted OR = 0.74, 95%CI = 0.56, 0.98) and excessive (adjusted OR = 0.69, 95%CI = 0.54, 0.98) gestational weight gain. The social spaces scale was also associated with decreased odds of living greater than 3 miles from a supermarket (adjusted OR = 0.03, 95%CI = 0.00, 0.27). Territoriality was not associated with any pregnancy-related health behavior. None of the neighborhood constructs were associated with smoking or diet quality. Physical incivilities and social spaces neighborhood characteristics may be important to measure to improve our understanding of the potential mechanisms through which neighborhood environments influence health.

Objective: It was recently demonstrated that synoviocytes (FLS) from rheumatoid arthritis (RA) patients express BAFF transcripts that are up-regulated by tumor necrosis factor alpha (TNFalpha) and interferon-gamma (IFNgamma). Thus, BAFF increases in RA target cells might be related to activation of the receptors of innate immunity. The purpose of this study was to determine whether ligands of Toll-like receptor 2 (TLR-2), TLR-4, TLR-9, and alpha5beta1 integrin are able to induce BAFF synthesis by RA FLS., Methods: Quantitative reverse transcription-polymerase chain reaction analyses and enzyme-linked immunosorbent assays were performed to evaluate BAFF messenger RNA induction and BAFF release from FLS after stimulation by ligands for TLR-2, TLR-4, TLR-9, alpha5beta1 integrin (bacterial lipopeptide [BLP] palmitoyl-3-cysteine-serine-lysine-4, lipopolysaccharide [LPS], CpG, and protein I/II, respectively), TNFalpha, and IFNgamma., Results: In contrast to IFNgamma, neither TNFalpha, LPS, BLP, nor CpG induced the de novo synthesis and release of BAFF by FLS. Priming of cells with IFNgamma did not have a synergistic effect on BAFF synthesis by FLS stimulated with bacterial products known as pathogen-associated molecular patterns. Moreover, we found that IFNgamma-induced BAFF synthesis is inhibited by simultaneous stimulation with either TLR ligands or TNFalpha. We also showed that interplay between TLRs, TNF receptors, and IFNgamma signaling induces the expression of suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 and reduces IFNgamma-dependent STAT-1 phosphorylation, which might explain this inhibition. In contrast, we demonstrated that stimulation of alpha5beta1 integrin can induce BAFF synthesis and release per se and that stimulation of this pathway has no inhibitory effect on IFNgamma-induced BAFF synthesis., Conclusion: Our findings indicate that BAFF secretion by resident cells in target organs of autoimmunity is tightly regulated by innate immunity, with positive and negative controls, depending on the receptors and the pathways triggered.

Background: Neighborhood characteristics have been associated with poor maternal and child health outcomes, yet conceptualization of potential mechanisms is still needed. Census data have long served as proxies for area level socioeconomic influences. Unique information captured by neighborhood inventories, mostly conducted in northern US and Canadian urban areas, has shown important aspects of the community environment that are not captured by the socioeconomic and demographic aggregated individual statistics of census data. In this paper, we describe a neighborhood data collection effort tailored to a southern urban area., Methods: This study used data from the Pregnancy, Nutrition and Infection (PIN) prospective cohort study to describe neighborhoods where low- and moderate-income pregnant women reside. Women who participated in the PIN study and who resided in Raleigh, NC and its surrounding suburbs were included (n = 703). Neighborhood attributes captured by the inventory included litter, housing condition, road condition, and social interactions that informed theoretical constructs of physical incivility, territoriality and social spaces. US Housing and Population Census 2000 data at the block group level were also assessed to identify the unique contribution of directly observed data. We hypothesize that neighborhood environments can influence health through psychosocial mediated pathways that lead to increased stress, or through disadvantage leading to poor neighborhood resources, or by protective attributes through increased social control., Results: Findings suggest that directly observed neighborhood attributes distinguished between different types of areas in which low-income pregnant non-Hispanic white and non-Hispanic black women lived. Theoretically informed scales of physical incivilities, territoriality and social spaces were constructed and found to be internally consistent. Scales were weakly associated indicating that these constructs capture distinct information about these neighborhoods. Physical incivilities, territoriality and social spaces scales were poorly explained by traditional census variables used to proxy neighborhood environment., Conclusion: If neighborhoods influence health through psychosocial mediated pathways then careful detailing of neighborhood attributes that contribute to stress or deterioration, beyond traditional socioeconomic status, are needed. We believe that measuring physical incivility, territoriality and social spaces as expressions of underlying issues of maintenance and social communication make important contributes to this field.

Background: Paget's disease is an uncommon epidermal cancer, affecting all skin regions wherever apocrine glands are present. It is divided into extramammary (EMPD) and mammary Paget's disease (MPD). It can be confined to the epithelium or may be associated with an underlying adenocarcinoma. The diagnosis is confirmed by skin biopsy and the treatment depends on characteristics of the underlying cancer. Surgery is the first-line treatment. Imiquimod, a topical immunomodulator, approved its efficiency in several skin neoplasms and has been shown as a safe treatment for EMPD. However, it has never been reported for the treatment of MPD., Observations: We report on two cases of EMPD and MPD successfully treated with imiquimod 5% cream., Conclusion: This non-surgical method may be considered as a primary treatment when Paget's disease is not associated with an underlying malignancy. The good prognosis with a long-term survival, the anatomic localization and the poor general condition of elderly people may favor imiquimod as an alternative treatment. On the other hand, it will reduce the extent of excision when it anticipates surgery.

Darbepoetin alfa is a novel erythropoiesis-stimulating protein with a two- to threefold longer half-life than recombinant human erythropoietin (epoetin) in adult patients with chronic kidney disease (CKD). This randomized, open-label, crossover study was conducted to determine the pharmacokinetic profile of darbepoetin alfa in pediatric patients with CKD. Twelve patients 3-16 years of age with CKD were randomized and received a single 0.5 micro g/kg dose of darbepoetin alfa administered intravenously (IV) or subcutaneously (SC). After a 14- to 16-day washout period, patients received an identical dose of darbepoetin alfa by the alternate route. After IV administration, the mean clearance of darbepoetin alfa was 2.3 ml/h per kg, with a mean terminal half-life of 22.1 h. After SC administration, absorption was rate limiting, with a mean terminal half-life of 42.8 h and a mean bioavailability of 54%. Comparison of these results with those from a previous study of darbepoetin alfa in adult patients indicated that the disposition of darbepoetin alfa administered IV or SC is similar in adult and pediatric patients, although absorption may be slightly more rapid in pediatric patients after SC dosing. The mean terminal half-life of darbepoetin alfa in this study was approximately two- to fourfold longer than that previously reported for epoetin in pediatric patients.

Objective: The aim of this multicenter, randomized, open-label study was to compare the pharmacokinetic and pharmacodynamic profiles of darbepoetin alfa, a new erythropoiesis-stimulating protein, and recombinant human erythropoietin (epoetin) after repeated intravenous dosing in patients with chronic kidney disease receiving hemodialysis., Methods: Forty-seven patients were randomized to receive darbepoetin alfa administered once weekly (n = 17) or 3 times weekly (n = 15) or epoetin administered 3 times weekly (n = 15) for up to 52 weeks. Pharmacokinetic profiles were measured during weeks 1 and 12 and at hemoglobin steady state (defined as a hemoglobin concentration within the target range for 4 consecutive weeks after week 12 with no change in study drug dose) or between weeks 36 and 40, whichever occurred first., Results: At each of the 3 time points evaluated, the terminal half-life of darbepoetin alfa was 2 to 3 times longer and the clearance approximately 4 times slower than those of epoetin. At week 12, the terminal half-life was 23.4 hours with darbepoetin alfa once weekly, 18.3 hours with darbepoetin alfa 3 times weekly, and 8.0 hours with epoetin 3 times weekly. The pharmacokinetics of darbepoetin alfa was not dependent on dose or time. Mean hemoglobin values at steady state were all approximately 11 g/dL, within the target range of 9.0 to 13.0 g/dL. Safety analyses revealed no differences between darbepoetin alfa and epoetin., Conclusions: The pharmacokinetic and pharmacodynamic profiles and safety data for darbepoetin alfa demonstrate that it can be administered less frequently than epoetin in patients with chronic kidney disease receiving hemodialysis, thus simplifying anemia management.

Mutations in the cytoplasmic Cu/Zn superoxide dismutase (SOD1) gene on human chromosome 21q22.1 cause 10-20% of familial amyotrophic lateral sclerosis (ALS) cases. The expression of the ALS phenotype in mice carrying the murine G86R SOD1 mutation is highly dependent upon the mouse genetic background. This is similar to the phenotypic variation observed in ALS patients containing identical SOD1 mutations. In the FVB/N background, mice expressing mG86R SOD1 develop an ALS phenotype at approximately 100 days. However, when these mice were bred into a mixed background of C57Bl6/129Sv, the onset of the ALS phenotype was delayed (143 days to >2 years). Using 129 polymorphic autosomal markers in a whole genome scan, we have identified a major genetic modifier locus with a maximum lod score of 5.07 on mouse chromosome 13 between D13mit36 and D13mit76. This 5- to 8-cM interval contains the spinal muscular atrophy (SMA)-associated gene Smn (survival motor neuron) and seven copies of Naip (neuronal apoptosis inhibitory protein), suggesting a potential link between SMA and ALS.

The North Carolina Native American Cervical Cancer Prevention Project was a 5-year (1989-1995) National Cancer Institute-funded, community-based, early detection of cervical cancer intervention implemented among two Native American tribes in North Carolina: the eastern band of the Cherokee Indians and the Lumbee. The initial quantitative analysis of the intervention showed modest effects and found that the intervention had different effects in the two communities. Due to the equivocal findings, a retrospective qualitative study was conducted. The qualitative study found that two types of factors influenced the intervention's results. The first were project and intervention characteristics, and the second were community and cultural factors over which the project had no control. The community and cultural factors took two forms: enhancers, which contributed to greater intervention effect, and attenuators, which created barriers to success. Examples of each factor are presented, and implications for cervical cancer detection among Native American women are discussed.

Early initiation of cigarette smoking so strongly predicts future smoking that several investigators have advocated delaying the age of initiation as a prevention strategy. To complement retrospective studies of early initiation, this study assessed prospectively patterns of smoking behavior in a sample of 401 children who were surveyed in the fifth, sixth, and seventh grades. The principal findings were (1) modeling of smoking by parents and friends is sufficient to influence children to initiate smoking, particularly when children also have low behavioral self-control, and (2) when modeling occurs in combination with poor adjustment to school, low parental monitoring, easy access to cigarettes, and other risk attributes, early initiators are significantly more likely to continue smoking. The results suggest that delaying initiation of smoking without also modifying child attributes and socialization factors that predict early initiation and persistent smoking is unlikely to reduce the proportion of children who become habitual smokers.

The porcine retinoic acid receptor-gamma gene (RARG) has been mapped by restriction fragment length polymorphism analysis to porcine chromosome 5. The placement of RARG distal to the diacylglycerol kinase gene increases the length of the existing map (PiGMaP) and adds a fifth type-I marker to this sparsely mapped chromosome. This augments the homology of pig chromosome 5 and human chromosome 12 established by previous comparative mapping.

The majority of men with cystic fibrosis (CF) are infertile due to a bilateral congenital absence of the vas deferens (CBAVD). However, clinically affected CF patients present a spectrum of genital phenotypes ranging from normal fertility to severely impaired spermatogenesis and CBAVD. Recently, it has become apparent that CF can manifest itself as isolated CBAVD in the absence of other clinical symptoms. The present study was undertaken to test the possible involvement of the CF gene in the aetiology of male infertility other than CBAVD. Semen specimens from 127 unrelated healthy males with various diagnoses of reduced sperm quality were screened for a panel of 13 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Fourteen of 80 (17.5%) healthy men with infertility due to reduced sperm quality and 3 of 21 (14.3%) men with azoospermia had at least one CF mutation (one azoospermic male was a compound heterozygote). The frequency of mutations in our sample of infertile males was significantly higher than the expected CF carrier frequency in the local population (P = 0.00139). No mutations were found in a control group of 26 individuals with normal semen parameters. This increased frequency of CF mutations in healthy men with reduced sperm quality and in men with azoospermia without CBAVD suggests that the CFTR protein may be involved in the process of spermatogenesis or sperm maturation apart from playing a critical role in the development of the epididymal glands and the vas deferens.

Maternal-fetal histocompatibility for alleles at HLA class II loci, HLA-DQA1 and HLA-DQB1, was examined in 40 abortuses and 31 liveborn children of 68 couples with a history of idiopathic recurrent spontaneous abortion (RSAB) who underwent leukocyte immunization prior to the index pregnancy. Significantly more couples with RSAB shared two HLA-DQA1 alleles as compared with fertile control couples (0.18 vs. 0.03, respectively; P = 0.031). There were no differences in HLA sharing between couples with RSAB who experienced a repeat abortion in the index pregnancy as compared with couples with RSAB who were delivered of a liveborn child. Non-significant deficits of abortuses who were compatible for alleles at the HLA-DQA1 (6 observed vs. 8.5 expected; P = 0.225) and the HLA-DQB1 (7 observed vs. 9.2 expected; P = 0.254) loci were observed. A significant deficit of HLA-DQA1 compatible liveborn children was observed (1 observed vs. 5.5 expected; P = 0.0069). The overall deficit of HLA-DQA1 compatible fetuses (7 observed vs. 14.0 expected; P = 0.0018) after approximately 8 weeks gestation suggests that HLA-DQA1 compatible fetuses may be aborted early in pregnancy, prior to the time when fetal tissue can be recovered for genetic studies.