[Disease-related knowledge acquisition through structured patient information in rheumatoid arthritis (StruPI-RA) : First results of the StruPI-RA study in Germany]. / Krankheitsbezogener Wissenserwerb durch strukturierte Patienteninformation bei Rheumatoider Arthritis (StruPI-RA) : Erste Ergebnisse der StruPI-RA-Studie in Deutschland.

BACKGROUND/OBJECTIVE: The structured patient information for rheumatoid arthritis (StruPi-RA) program was the first standardized outpatient education program in rheumatoid arthritis (RA) in Germany. The main objective of the study was to determine the efficacy of the StruPi-RA program concerning disease-specific knowledge acquisition in patients with early stage RA or after changing the treatment regimen. METHODS: A total of 61 patients were included in a control group design, 32 in the intervention group (IG) and 29 in the control group (CG). Patients of the IG attended 3 modules of 90 min in a structured patient information program (StruPI-RA) including the topics of diagnostics, treatment and living with RA. Patients in the CG only received information material from the German Rheumatism League. The primary target criterion was the disease-related acquisition of knowledge, measured with the patient knowledge questionnaire (PKQ). Data were collected before and after participation in StruPI-RA. RESULTS: The improvement in knowledge in the IG attending the StruPI-RA compared to the CG was significant in time and group comparisons. No influence of disease duration or educational level was observed. The subscale treatment alone showed a significant difference in the group and time comparison. CONCLUSION: Participation in the StruPI-RA program in early RA was associated with a significant increase in disease-specific knowledge compared to the control group of patients. This leads to better decision-making in terms of treatment, a more beneficial doctor-patient communication and better self-management. In the long term an improvement in treatment adherence and quality of life is expected.

A collaborative care model to improve access to pediatric mental health services.

To examine if an innovative collaborative care model known as Targeted Child Psychiatric Services designed for primary care pediatricians (PCPs) and child psychiatrists (1) was associated with improved access to child psychiatry services, (2) had the potential to identify optimal care settings for pediatric mental health care and (3) examined if pediatricians appeared as likely to accept children back into their practices at discharge from TCPS depending upon diagnostic category, controlling for severity of illness and function. The diagnostic classes examined were ADHD (39%), depression (31%) and anxiety (13%). This prospective cohort design study collected medical records of 329 children referred to TCPS by 139 PCPs. To detect the likelihood of return to referring pediatricians for follow-up care at discharge from TCPS, we employed logistic regression models. Mean age was 12.3 (SD = 4.0); 43% were female. Ninety-three percent of parents complied with pediatricians' recommendations to have their child assessed by a child psychiatrist. A total of 28.0% of referrals returned to PCPs for follow-up care; the remainder were followed in mental health. Regression findings indicated that children with major depression (OR = 7.5) or anxiety disorders (OR = 5.1) were less likely to return to PCPs compared to ADHD even though severity of psychiatric illness and functional levels did not differ across diagnostic groups. Families widely accepted pediatricians' recommendations for referral to child psychiatrists. Depression and anxiety were strong correlates of retention in mental health settings at discharge from TCPS though children with these disorders appeared to be no more severely ill or functionally limited than peers with ADHD. These children possibly could be managed in a less intensive and expensive primary care treatment setting that could access mental health specialty services as needed in a collaborative model of care. TCPS is contrasted with the well-known collaborative model for adult depression in primary care. TCPS could serve as a feasible model of care that addresses the daunting barriers in accessing pediatric mental health services.

Coenzyme A dithioesters: synthesis, characterization and reaction with citrate synthase and acetyl-CoA:choline O-acetyltransferase.

Acyl dithioesters of CoA have been synthesized by transesterification. The alpha-hydrogens have a spectrally determined pKa of 12.5 +/- 0.14. The hydroxide catalyzed enolization rate is estimated to be 600 M-1.s-1. The absorbance of the dithioester, lambda max = 306 nm, can be used to monitor both the condensation and transesterification reactions that use CoA-Ac as a substrate. For citrate synthase at pH 7.4 Vmax = (4.0 +/- 0.4).10(-4) s-1 and Km = 53 +/- 7.5 microM, which are 2.10(-6) and 3.3-times the Vmax and Km values observed for CoAS-Ac, while for Ac-CoA: choline O-acetyltransferase (EC 2.3.1.6) at pH 7.0 Vmax = (1.1 +/- 0.2).10(-2) mumol.s-1.(mg protein)-1 and Km = 83 +/- 33 microM, which are 0.077 and 10-times the values observed with CoAS-Ac, respectively. The CoA dithioesters are stable at low pH, but hydrolyze with a second-order rate constant of 8.2.10(-2) M-1.s-1 at pH 11.4. The spectral properties of these dithioesters should allow these analogs to be used as probes of the structure of enzyme bound intermediates.

Hyperexpressed hairy leukemic cell Ii might bind to the antigen-presenting site of class II MHC molecules.

The p35 protein which is hyperexpressed on hairy leukemic cells was determined to be Ii, the electrophoretically invariant glycoprotein that is associated with class II major histocompatibility complex (Ia) antigens from the time of their synthesis. The principal function of class II MHC antigens is to present to T cell receptors those digested foreign antigenic peptides that probably fold as amphipathic alpha-helices and adsorb to a hydrophobic surface (desetope) on Ia. By a novel strip-of-helix hydrophobicity algorithm we found that the sequence Leu-142 to His-170 in Ii formed a five-cycle, amphipathic, alpha-helix, the highest scoring one among a series of proteins commonly used as experimental antigens. This finding led to the hypothesis that this sequence in Ii bound to the antigen-binding site (desetope) of Ia until release and self-aggregation in the endosome in order that digested foreign peptides could then bind to Ia. Abundant expression of Ii in leukemic cells might be associated with an altered capacity of those cells to present foreign or leukemic antigens to the host's immune system.

Hydrophobic strip-of-helix algorithm for selection of T cell-presented peptides.

In extension of the hypothesis that an amphipathic alpha helix of Ii (Phe146-Val164) bound to the foreign antigen-presenting site (desetope) of class II MHC molecules through hydrophobic amino acid residues (Phe146, Leu150, Leu153, Met157, Ile160, Val164) which were present in an axial strip along one side of the Ii helix, we developed an algorithm to search for T cell-presented peptides showing a similar hydrophobic strip-of-helix. Such peptides might bind to the class II MHC molecule site which was complementary to the Ii hydrophobic strip-of-helix. The strip-of-helix hydrophobicity index was the mean hydrophobicity (from Kyte-Doolittle values) of sets of amino acids in axial strips down sides of helices for 3-6 turns, at positions, n, n + 4, N + 7, n + 11, n + 14, and n + 18. Peptides correlating well with T cell responsiveness had: (1) 12-19 amino acids (3-5 cycles or 4-6 turns of an alpha helix), (2) a strip with highly hydrophobic residues, (3) adjacent, moderately hydrophilic strips, and (4) no prolines. The degree of hydrophilicity of the remainder of a putative antigenic helix above a threshold value did not count in this index. That is, the magnitude of amphipathicity was not judged to be the principal selecting factor for T cell-presented peptides. This simple algorithm to quantitate strip-of-helix hydrophobicity in a putative amphipathic alpha helix, allowing otherwise generally hydrophilic residues, predicted 10 of 12 T cell-presented peptides in seven well-studied proteins. The derivation and application of this algorithm were analyzed.

Mixed-field neutrons and gamma photons induce different changes in ileal bacteria and correlated sepsis in mice.

High doses of radiation induce septicaemia, from bacterial translocation, and death in animals. Mice were exposed to either comparable lethal (LD90/30) or sublethal (LD0/30) doses of mixed-field [n/(n + y) = 0.67] or pure 60Co gamma-photon radiation. The relative biological effectiveness of these comparable doses of radiation was 1.82, determined by probit analysis. Mice given a lethal dose of mixed-field radiation developed a significant (p < 0.01), 10(9)-fold increase in Gram-negative facultative bacteria in their ilea over values in control mice. In contrast, mice given a lethal dose of gamma-photon radiation developed a significant (p < 0.01) increase in only Gram-positive bacteria in their ilea, while the number of Gram-negative bacteria remained near values in control mice. Data correlated with bacteria that were isolated and identified from the livers of mice that were given comparable lethal doses (LD99/30) of mixed-field or gamma-photon radiation. In sublethally irradiated mice, fluctuation in the total number of bacteria was detected in their ilea during the first week following irradiation, after which the number approximated the value in control mice. This difference in the predominant facultative bacteria in ilea resulting from different qualities of radiation has important implications for the treatment of septicaemic-irradiated hosts.

A simple provider-based educational intervention to boost infant immunization rates: a controlled trial.

We sought to determine if a simple educational intervention initiated at the first well-child care visit, with reinforcement at subsequent visits, can improve inner-city infant immunization rates. We conducted a controlled trial involving 315 newborn infants and their primary caregivers in 3 inner-city primary care centers. Child health care providers gave caregivers in the intervention group an interactive graphic card with verbal reinforcement. At later visits, stickers were applied to the card when immunizations were given. Routine information was given to controls. After the trial, age-appropriate immunization rates at 7 months were 58% in each group. Intervention infants had 50% fewer missed opportunities to immunize (p=0.01) but cancelled 77% more appointments (p=0.04) than controls. We conclude that a brief educational intervention at the first well-child care visit did not boost 7-month immunization rates, although it was associated with fewer missed opportunities to immunize.

Determining immunization rates for inner-city infants: statewide registry data vs medical record review.

OBJECTIVE: This study evaluated the benefit of consulting a statewide immunization registry for inner-city infants whose immunizations appeared, after single-site chart review, to have been delayed. METHODS: We prospectively enrolled 315 newborns in 3 inner-city pediatric clinics. When the infants turned 7 months old, we obtained immunization data from clinic charts and the state registry. RESULTS: On the basis of chart review, 147 infants (47%) were assessed to be delayed in their immunizations; of these, registry data revealed that 28 (19%) had received additional immunizations and 15 (10%) were actually up to date. CONCLUSIONS: A statewide registry can capture immunizations from multiple sources, improving accurate determination of immunization rates in a mobile, inner-city population.

Methylxanthine treatment of smooth muscle cells differentially modulates adenylate cyclase responsiveness.

The DDT1 MF-2 smooth muscle cell line was used to study regulation of the A1 and A2 adenosine receptor (AR)-adenylate cyclase system by two different methylxanthines. 3-isobutyl 1-methylxanthine (IBMX) is both an AR antagonist and a phosphodiesterase inhibitor, while xanthine amine congener is an AR antagonist without phosphodiesterase activity. Incubation of cells for 18 hr with 100 microM IBMX produced a significant (P less than .05) decrease in the basal, isoproterenol- and sodium fluoride-stimulated adenylate cyclase activity. This generalized decrease in adenylate cyclase activity was associated with a significant decrease in the quantity of alpha s (Gs) as determined by Western blotting. In contrast, no alteration in alpha i (Gi) was observed in these same membranes. A significant increase in both the quantity of A1AR and the receptors' affinity for agonist occurred; however, no alteration in the ability of an A1AR selective agonist to inhibit adenylate cyclase activity was observed. Treatment for 18 hr with 50 nM xanthine amine congener, conversely, resulted in an increase in basal and isoproterenol stimulated adenylate cyclase activity with no change in membrane alpha s (Gs). With IBMX, there was an increase in agonist affinity for the A1AR without an associated change in the effect of adenosine agonists on adenylate cyclase activity. These data indicate that methylxanthine analogs which lack the ability to inhibit phosphodiesterases regulate receptor-mediated transmembrane signaling systems quite differently from those possessing such characteristics. The more prototypic methylxanthines regulate both receptors and G proteins in these smooth muscle cells.

An hypothesis on the binding of an amphipathic, alpha helical sequence in Ii to the desetope of class II antigens.

When we investigated the hypothesis that amphipathic alpha helical peptides digested from foreign antigen bind to class II major histocompatability complex (MHC) molecules' binding site (desetope) for foreign antigen to be presented to T cell receptors, we found such an extended amphipathic helix in Ii. This amphipathic helix was hypothesized to bind Ii to class II MHC antigens until release in endosomes containing digested foreign antigen. Then these amphipathic Ii polypeptides might polymerize so as not to compete with foreign antigen for binding to class II MHC molecules. Various structural models were consistent with these views and led to the suggestion of specific forms of polymeric interaction.