Screening for diabetic retinopathy in primary care with a mobile fundal camera--evaluation of a South African pilot project.

BACKGROUND AND AIMS: In South Africa diabetes makes a significant contribution to the burden of disease. Diabetic retinopathy is a leading cause of adult blindness, and screening can reduce the incidence. This project aimed to implement and evaluate a new service for retinal screening that uses a non-mydriatic mobile fundal camera in primary care. This is the first time such a service has been evaluated in an African primary care context. METHODS: The service was implemented as an operational research study at three community health centres and data were collected to evaluate the operational issues, screening, reporting and referral of patients. RESULTS: Out of 400 patients screened 84% had a significantly reduced visual acuity, 63% had retinopathy (22% severe nonproliferative, 6% proliferative and 15% maculopathy), 2% of eyes could not be screened and 14% of patients required dilatation. Referral was necessary in 27% of cases for cataracts, in 7% for laser treatment and in 4% for other specialist services. Repeat photography was needed in 8% and urgent follow-up in 12%. A SWOT analysis of the pilot project was completed and recommendations were made on how to integrate it into the district health system. CONCLUSION: Screening with a fundal camera improved the quality of care for diabetic patients and is feasible in the South African public sector, primary care setting. A single technician should be able to photograph almost 10,000 patients a year.     

Development of Activity Assays for High-Volume Evaluation of Human Immunodeficiency Virus (HIV) Protease Inhibitors in Rat Serum: Results with Ditekiren

We showed previously that a commercially available synthetic tetradecapeptide, Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser, produces authentic angiotensin I (Ang I) upon incubation with the HIV-1 protease (S. K. Sharma et al., Anal. Biochem. 198:363, 1991). Therefore, we developed an Ang-I based activity assay for HIV protease inhibitors based on the technology developed earlier (M. J. Ruwart et al., Pharm. Res. 7:407, 1990; S. K. Sharma et al., Anal. Biochem. 186:24, 1990) for tracking renin inhibitors in rat sera. Ditekiren was either extracted from sera with ethyl acetate or assayed after the interfering substances in sera were precipitated with acetonitrile. Purified recombinant HIV-1 protease was added to extracted rat serum and the enzymatic reaction was initiated in the presence of the tetradecapeptide substrate. The inhibition of Ang I production was measured by a commercially available RIA kit. The cleanup methodology also enabled a commercially available Proteinase Scintillation Proximity Assay (SPA, Amersham) to quantify ditekiren in rat serum through the addition of recombinant HIV-1 protease and cleavage of substrate from SPA beads. Results were confirmed by HPLC or by the renin assay for ditekiren, which inhibits both aspartyl proteases. These technologies should prove useful for assessing serum levels of HIV protease inhibitors in rat.     

Pulsed magnetization transfer spin-echo MR imaging

Cross relaxation between macromolecular protons and water protons is known to be important in biologic tissue. In magnetic resonance (MR) imaging sequences, selective saturation of the characteristically short T2 macromolecular proton pool can produce contrast called magnetization transfer contrast, based on the cross-relaxation process. Selective saturation can be achieved with continuous wave irradiation several kilohertz off resonance or short, intense 0° pulses on resonance. The authors analyze 0° binomial pulses for T2 selective saturation, present design guidelines, and demonstrate the use of these pulses in spin-echo imaging sequences in healthy volunteers and patients. Using the phenomenologic Bloch equations modified for two-site exchange, the authors derive the analytic expressions for water proton relaxation under periodic pulsed saturation of the macromolecular protons. This relaxation is shown to be monoexpo-nential, with a rate constant dependent on the saturation pulse repetition rate and the individual and cross-relaxation rates.     

Mauve: multiple alignment of conserved genomic sequence with rearrangements

As genomes evolve, they undergo large-scale evolutionary processes that present a challenge to sequence comparison not posed by short sequences. Recombination causes frequent genome rearrangements, horizontal transfer introduces new sequences into bacterial chromosomes, and deletions remove segments of the genome. Consequently, each genome is a mosaic of unique lineage-specific segments, regions shared with a subset of other genomes and segments conserved among all the genomes under consideration. Furthermore, the linear order of these segments may be shuffled among genomes. We present methods for identification and alignment of conserved genomic DNA in the presence of rearrangements and horizontal transfer. Our methods have been implemented in a software package called Mauve. Mauve has been applied to align nine enterobacterial genomes and to determine global rearrangement structure in three mammalian genomes. We have evaluated the quality of Mauve alignments and drawn comparison to other methods through extensive simulations of genome evolution.     

Paradoxical effects of interleukin-10 on the maturation of murine myeloid dendritic cells

The immunoregulatory cytokine, interleukin-10 (IL-10), has been shown to inhibit the maturation of human myeloid dendritic cells (DC). In the present study, we demonstrate that IL-10 has paradoxical effects on the maturation of murine myeloid bone marrow-derived DC. On the one hand, IL-10 inhibits the maturation of murine myeloid DC. The addition of IL-10 to granulocyte-macrophage colony-stimulating factor (GM-CSF)-supported murine BM-derived DC cultures reduced the frequency of major histocompatibility complex (MHC) class IIbright cells. These IL-10-pretreated DC have a reduced capacity to stimulate T cells in an allogeneic mixed leucocyte reaction. On the other hand, however, and in contrast to the effects of IL-10 on human DC, we found that the addition of IL-10 from the initiation of the culture onwards induced an up-regulation of the expression of the costimulatory molecules CD40, CD80 and CD86 on murine myeloid DC, as compared to DC generated with GM-CSF only. Moreover, a subpopulation of IL-10-pretreated MHC class IIdim DC lacked the capacity to take up dextran-fluorescein isothiocyanate (FITC), a feature of DC maturation. Taken together, our data demonstrate that the generation of murine myeloid DC in the presence of IL-10 results in a population of incompletely matured MHC class IIdim CD80+ CD86+ DC. These DC lack T-cell stimulatory capacity, suggesting a role for IL-10 in conferring tolerogenic properties on murine myeloid DC.     

Pain and disability in osteoarthritis: A review of biobehavioral mechanisms

Pain and disability are cardinal symptoms in osteoarthritis. The literature is reviewed in order to identify causes of these symptoms at the articular, kinesiological, and psychological level. It is concluded that pain and disability are associated with degeneration of cartilage and bone (articular level), with muscle weakness and limitations in joint motion (kinesiological level), and with anxiety, coping style, attentional focus on symptoms, and possibly depression (psychological level). Biobehavioral mechanisms of pain and disability which explain the observed associations are described and the empirical evidence for these mechanisms is evaluated. Methodological and conceptual deficiencies in the research reviewed are pointed out and suggestions for further research are given.     

Are planning,working memory,and inhibition associated with individual differences in preschool ADHD symptoms?

The association between executive function (EF; planning, working memory, and inhibition) and individual differences in symptoms of attention deficit hyperactivity disorder (ADHD) was explored in a sample of preschool children. One hundred sixty children (between the ages of 3 years, 0 months and 5 years, 6 months), selected so as to oversample high ADHD scorers, performed 3 tasks previously shown to measure planning (Tower of London), working memory (Noisy Book) and inhibition ("Puppet Says..."). EF measures were reliable (kappa > .77) and were correlated with IQ (rs > .38) and age (rs > .59). Once IQ and age were controlled, planning and working memory (r = .41) were correlated. Planning and working memory were not correlated with inhibition (rs < .20). There was no association between ADHD and working memory or planning (rs < .12). There was a significant negative association between ADHD and conduct problems and inhibition (r = -.30 and r = -.25, respectively). Only the link with ADHD persisted after the effects of other factors were controlled for in a multiple regression. Specific deficits in inhibitory control rather than general EF deficits are associated with ADHD in the preschool period. This association is linear in nature, supporting the idea that ADHD is better seen as a continuum rather than a discrete category. This association provides evidence for Barkley's (1997) view that ADHD is underpinned by inhibitory deficits in the preschool period.