Experimental infection of different species of birds with pigeon paramyxovirus type 1 virus--evaluation of clinical outcomes, viral shedding, and distribution in tissues.

The virulence of pigeon paramyxovirus type 1 (PPMV-1) for different species of birds was investigated in two independent sets of experiments in which groups of pigeons, chickens, turkeys, quails, and geese (10 birds per group) were inoculated with 10(6) median embryo infectious doses of PPMV-1 isolate: 1) nonpassaged (nPPMV-1, intracerebral pathogenicity [ICPI] value = 1.27) and 2) after six passages in specific-pathogen-free chickens (pPPMV-1, ICPI = 1.46) via the oculonasal route. Naive birds were placed in contact with infected birds (two birds per group) to monitor virus transmission. Clinical observation was performed daily. Additionally, cloacal swabs, oropharyngeal swabs, and selected organ samples were collected on days 2, 4, 7, 10, and 14 postinfection and tested by real-time reverse transcriptase-PCR for estimation of viral shedding and distribution in tissues. Infected pigeons exhibited nervous and digestive tract symptoms, mortality, shedding, and transmission to contact birds. Chickens, turkeys, quails, and geese did not exhibit any clinical signs regardless of the PPMV-1 strain used for inoculation. However, in contrast to quails and geese, chickens and turkeys shed the virus via the oral cavity and cloaca, and transmission to contact birds was also observed. Viral RNA was identified in tissues collected from all pPPMV-1-infected birds, whereas negative results were obtained in the case of tissues taken from nPPMV-1-infected quails and geese. We conclude that the PPMV-1 used in this study was most virulent to pigeons, followed by chickens and turkeys, while quails and geese seem to have the highest level of innate resistance to this strain. However, passaging of PPMV-1 in chickens resulted in the increase of ICPI and noticeable but sometimes contrasting changes in the replication capacities of the virus.

Study design and baseline description of the BMI2 trial: reducing paediatric obesity in primary care practices.

OBJECTIVES: This study will test the efficacy of motivational interviewing (MI) conducted by primary care providers and dieticians among children ages 2-8 years old with a body mass index (BMI) ≥ 85th and ≤ 97th percentile. METHODS: Forty-two practices from the American Academy of Pediatrics, Pediatric Research in Office Settings Network were assigned to one of three groups. Group 1 (usual care) measures BMI percentile at baseline, and at 1- and 2-year follow-ups and receives standard health education materials. Group 2 providers deliver three proactive MI counselling sessions with a parent of the index child in Year 1 and one additional 'booster' visit in Year 2. Group 3 adds six MI counselling sessions from a trained dietician. The primary outcome is the child's BMI percentile at 2-year follow-up. Secondary outcomes include parent report of the child's screen time, physical activity, intake of fruits and vegetables, and sugar-sweetened beverages. RESULTS: We enrolled 633 eligible children whose mean BMI percentile was 92.0 and mean age of 5.1. The cohort was 57% female. Almost 70% of parents reported a household income of ≥ $40,000 per year, and 39% had at least a college education. The cohort was 63% white, 23% Hispanic, 7% black and 7% Asian. Parent self-reported confidence that their child will achieve a healthy weight was on average an 8 (out of 10). CONCLUSION: To date, several aspects of the study can inform similar efforts including our ability to use volunteer clinicians to recruit participants and their willingness to dedicate their time, without pay, to receive training in MI.

Note: Achieving quasi-hydrostatic conditions in large-volume toroidal anvils for neutron scattering to pressures of up to 18 GPa.

We present developments that allow neutron-scattering experiments to be performed, with both single-crystal and powder samples, under quasi-hydrostatic conditions to pressures beyond previous limits. Samples of sodium chloride and squaric acid (H(2)C(4)O(4)) have been loaded with argon as the pressure-transmitting medium in encapsulated gaskets redesigned for double-toroidal anvils, using a gas-loading method at ambient temperature. These samples have been compressed up to 18 GPa in a Paris-Edinburgh press, and no evidence of peak broadening in either the single-crystal or the powder experiments was observed.

Gas loading apparatus for the Paris-Edinburgh press.

We describe the design and operation of an apparatus for loading gases into the sample volume of the Paris-Edinburgh press at room temperature and high pressure. The system can be used for studies of samples loaded as pure or mixed gases as well as for loading gases as pressure-transmitting media in neutron-scattering experiments. The apparatus consists of a high-pressure vessel and an anvil holder with a clamp mechanism. The vessel, designed to operate at gas pressures of up to 150 MPa, is used for applying the load onto the anvils located inside the clamp. This initial load is sufficient for sealing the pressurized gas inside the sample containing gasket. The clamp containing the anvils and the sample is then transferred into the Paris-Edinburgh press by which further load can be applied to the sample. The clamp has apertures for scattered neutron beams and remains in the press for the duration of the experiment. The performance of the gas loading system is illustrated with the results of neutron-diffraction experiments on compressed nitrogen.

A comparative study of P53/MDM2 genes alterations and P53/MDM2 proteins immunoreactivity in liver cirrhosis and hepatocellular carcinoma.

In the present study, the expression of P53 and MDM2 proteins were examined in specimens from a group of 20 patients (9 with primary hepatocellular carcinoma HCC and 11 with liver cirrhosis LC, linked to HBV infections as a major aetiologic factor) by immunohistochemistry. The immunostaining findings were correlated with P53 mutation analysis using PCR-SSCP, PCR-HDF and direct sequencing, and MDM2 amplification studies by differential PCR. P53 immunopositivity was found in 9 out of the 20 (45.0%) cases. Mutations of the P53 gene were detected in 5 (55%) tumors and 3 (27%) LC samples; 7 of these cases revealed P53 immunoreactivity. The mutations were base transitions at codons 175, 245 and 273; no changes were observed at codon 249, characteristic for aflatoxins action. MDM2 immunopositivity was revealed in 9 out of 20 (45.0%) specimens. MDM2 amplification occurred in 4 (44.4%) and 1 (9.1%) cases, HCC and LC specimens respectively; only in 2 tumors (10.0%), which exhibited MDM2 immunoreactivity. Overall, MDM2 positivity was not associated with MDM2 amplification in 7 out of the 20 studied samples (35.0%). Two HCC patients were found to have both gene abnormalities. Either the mutation rate of the P53 gene as well as the amplification level of the MDM2 gene was higher in HCC than in precancerous liver tissue stages. These results support the notion that besides P53 alterations, MDM2 gene deregulation seems to be an important event in hepatocarcinogenesis. Additionally, the mechanism of MDM2-mediated degradation of P53 protein, without involving stabilization and inactivation of P53 gene, should be considered for the understanding of all features of tumor progression processes.

Impact of the change to inactivated poliovirus vaccine on the immunization status of young children in the United States: a study from pediatric research in office settings and the National Medical Association.

OBJECTIVE: To determine whether the change from an all oral poliovirus vaccine (OPV) schedule to an inactivated poliovirus vaccine (IPV)-containing schedule has adversely affected the immunization status of young children in the United States. METHODS: Immunization data were abstracted from the medical records of children 8 to 35 months old seen consecutively for any reason in the offices of practicing pediatricians who are members of the Pediatric Research in Office Settings network of the American Academy of Pediatrics or the National Medical Association. Data on up to 120 eligible children were collected in each practice between March 1998 and January 2000. Patients were classified as fully immunized at 8 months old if they had received 3 diphtheria-tetanus-pertussis, 2 Haemophilus influenzae type b, 2 hepatitis B, and 2 poliovirus vaccines. Study children who were >/=12 months of age at the time that data were collected were categorized as being fully immunized at 12 months if they had received the same vaccines before their first birthday. To assess the effect of type of poliovirus vaccines on these outcomes, study patients were classified as being in an IPV or OPV group based on the initial type of vaccine received. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for IPV as a predictor of being fully immunized at 8 and 12 months of age, after adjusting for race/ethnicity of the patient, maternal education level, year of birth, and method of payment for vaccines. In addition, the effect of clustering of children within practices was accounted for by the use of generalized estimation equation techniques. RESULTS: Data were analyzed on 13 520 children from 177 practices in 42 states; 79.4% of patients were fully immunized at 8 months of age, and 88.7% of those eligible were fully immunized at 12 months of age. A total of 6910 patients (51.1%) were classified as OPV recipients, wheras 5282 (39.1%) received IPV. In addition, 1328 children (9.8%) were documented as having received poliovirus vaccine, but the particular type could not be determined. Compared with OPV recipients and after controlling for the confounding variables and the effect of clustering within practices, children in the IPV group were as likely as were OPV recipients to be fully immunized at 8 months of age (OR: 1.04; 95% CI: 0.88,1.23). At 12 months of age, the OR for IPV as a predictor of being fully immunized was 1.08 (95% CI: 0.90,1.30). When compared with OPV recipients, adjusted ORs for children in the undetermined poliovirus vaccine type group being fully immunized at 8 and 12 months of age were 0.84 (95% CI: 0.68,1.04) and 0.84 (95% CI: 0.67,1.07), respectively. CONCLUSIONS: The results of this national study indicate that the implementation of an IPV-containing poliovirus vaccine schedule has not had an adverse effect on the immunization status of young children who were vaccinated in the offices of practicing pediatricians.

Coordination of specialty referrals and physician satisfaction with referral care.

OBJECTIVES: To describe how physicians coordinate patient care for specialty referrals and to examine the effects of these activities on referring physicians' satisfaction with the specialty care their patients receive and referral completion. DESIGN AND METHODS: Prospective study of a consecutive sample of referrals (N = 963) made from the offices of 122 pediatricians in 85 practices in a national practice-based research network. Data sources included a physician survey completed when the referral was made (response rate, 99%) and a physician survey and medical record review conducted 3 months later (response rate, 85%). Referral completion was defined as receipt of written communication of referral results from the specialist. RESULTS: Pediatricians scheduled appointments with specialists for 39.3% and sent patient information to specialists for 50.8% of referrals. The adjusted odds of referral completion were increased 3-fold for those referrals for which the pediatrician scheduled the appointment and communicated with the specialist compared with those for which neither activity occurred. Referring physicians' satisfaction ratings were significantly increased by any type of specialist feedback and were highest for referrals involving specialist feedback by both telephone and letter. Elements of specialists' letters that significantly increased physician ratings of letter quality included presence of patient history, suggestions for future care, follow-up arrangements, and plans for comanaging care; only the inclusion of plans for comanaging patient care was significantly related to the referring physicians' overall satisfaction. CONCLUSIONS: Better coordination between referring physicians and specialists increases physician satisfaction with specialty care and enhances referral completion. Improvements in the referral process may be achieved through better communication and collaboration between primary care physicians and specialists.

The pediatric primary-specialty care interface: how pediatricians refer children and adolescents to specialty care.

OBJECTIVE: To describe how pediatricians refer patients to specialists, including frequency of referral decisions, reasons for referral, and types of referrals. DESIGN: We conducted a prospective study of visits (N = 58 771) made to 142 pediatricians in a national primary care practice-based research network. During 20 consecutive practice days, physicians and parents completed questionnaires for referred patients, and office staff kept logs of all visits. Physicians used medical records to complete questionnaires 3 months after referrals were made. RESULTS: Pediatricians referred patients to specialists during 2.3% of office visits. Referrals made during telephone conversations with parents accounted for 27.5% of all referrals. The most common reason for referral was advice on diagnosis or treatment (74.3%). Referrals were made most commonly to surgical subspecialists (52.3%), followed by medical subspecialists (27.9%), nonphysicians (11.4%), and mental health practitioners (8.4%). Physicians requested a consultation or a referral with shared management in 75% of cases. Otitis media was the condition referred most often (9.2%). Fifty other conditions accounted for 84.3% of all referrals. CONCLUSIONS: About 1 in 40 pediatric visits result in referral. Getting advice from a specialist is the most common reason for referral. Pediatricians desire a collaborative relationship with specialists for most of their referred patients. Physician training to increase clinical competence may be most useful for the 50 most commonly referred conditions. Education concerning the referral process should focus on the respective roles of the referring physician and specialist, particularly as they pertain to successful approaches for comanaging referred patients.

Identification of attentional and hyperactivity problems in primary care: a report from pediatric research in office settings and the ambulatory sentinel practice network.

OBJECTIVES: To 1) determine the frequency of identification of attentional and hyperactivity problems (AHPs) by clinicians, and 2) examine whether minority children or children from less well-educated, lower-income, or lower-functioning families would be more likely to be identified as having AHPs. DESIGN: Prospective cohort study of 22 059 consecutive children 4 to 15 years of age being seen for acute, chronic, and health supervision visits. SETTING: Practices of 401 pediatric and family practice clinicians in 44 states, Puerto Rico, and 4 Canadian provinces. METHODS: Parent questionnaires included demographic information and the Pediatric Symptom Checklist. Clinician questionnaires categorized psychosocial problems and addressed how assessment of problems was made. Analyses compared children with newly identified AHPs with those with other newly identified psychosocial problems. RESULTS: Clinicians identified behavior problems in 18.7% of children, with 9.2% of the entire sample identified as having AHPs. Among those with newly assessed AHPs, clinicians identified minority children and those from low-income or poorly functioning families as having AHPs at the same rate as other children. However, even after controlling for symptoms, males were more likely than females (odds ratio, 2.81) to be identified as having AHPs. Older clinicians were significantly more likely to identify children as having AHPs (odds ratio, 2.09). In assessing AHPs, clinicians used standardized tools such as behavioral questionnaires for only 36.9% of children, and Diagnostic and Statistical Manual criteria for 38.3% of children. CONCLUSIONS: AHPs are highly prevalent in primary care practice. Clinicians do not appear predisposed to label children from disadvantaged backgrounds as having AHPs. Primary care assessment of AHPs lacks standardization.

Size and age-sex distribution of pediatric practice: a study from Pediatric Research in Office Settings.

OBJECTIVES: To estimate (1) the average number of patients per practitioner in Pediatric Research in Office Settings, the national practice-based research network of the American Academy of Pediatrics; (2) the total number of active patients cared for in the network; and (3) the age-sex distribution of patients seen in pediatric practice. SETTING: Eighty-nine practices in 31 states with 373 Pediatric Research in Office Settings practitioners (59% of Pediatric Research in Office Settings members). METHODS: Practices were asked to enumerate the number of patients visiting the practice during the 2-year period from January 1, 1991, through December 31, 1992. Patients making multiple visits were counted only once, resulting in a patient count rather than a visit count. Age-sex registers were completed using computer billing records or medical record sampling. RESULTS: Study participants cared for 529513 active patients (50.7% male). Each practitioner cared for an average of 1546 patients. The number of patients per practitioner was significantly higher in less-populated areas and in solo practices. Children aged 12 years and younger comprised 81% of the patients seen by Pediatric Research in Office Settings practitioners, and more than half of the children were aged 6 years or younger. Before age 5 years, boys accounted for a slightly, but significantly, higher number of patients, whereas after age 14 years, girls comprised a significantly larger proportion of patients. CONCLUSIONS: The average number of 1546 patients per practitioner derived from these private practice data is in line with health maintenance organization-based estimates. Pediatric practitioners predominantly serve younger children. These data provide the only current national estimates of the size and age-sex distribution of independent pediatric practices, and can help pediatricians and health service researchers plan for the future provision of health care to children.

Pediatric research in office settings (PROS): a national practice-based research network to improve children's health care.

OBJECTIVES: To describe the establishment of a national pediatric primary care research network to improve children's health care-Pediatric Research in Office Settings (PROS), and to evaluate the network's progress toward achieving its objectives. SETTING: Pediatric practices in all 50 states and Puerto Rico. PARTICIPANTS: Approximately 1400 pediatric practitioners from more than 470 practices. RESULTS: Beginning in 1986, a core of volunteer pediatrician coordinators from participating American Academy of Pediatrics chapters were identified to oversee local PROS efforts, represent practitioners, and inform the development of proposed research studies. PROS subsequently recruited practitioners from around the country, building a research infrastructure and a system of collaboration between the practitioners, research staff at the AAP, and investigative teams at academic institutions. This PROS collaboration has developed and conducted 10 primary care research studies that have added to the knowledge base of pediatric primary care. CONCLUSIONS: PROS has accomplished two of its initial objectives-development of a structure and process for pediatric practice-based research and provision of research experience to practitioners. Successful and consistent achievement of a third objective-meaningful dissemination of study results to relevant audiences-will depend on meeting several challenges.