The Jamaican Haemophilia Registry: Describing the burden of disease.

INTRODUCTION: Jamaica has an estimated 200 persons with haemophilia (PWH), who face significant constraints in access to specialized haemophilia care, including access to clotting factor concentrates. AIM: The aim of this paper is to establish the current burden of disease in PWH in Jamaica. METHODS: PWH were enrolled through the University Hospital of the West Indies, Jamaica. The impact of haemophilia was assessed using a comprehensive battery of heath outcome measures that included the following: laboratory, clinical information and validated outcome measures of joint structure and function, activity, and health-related quality of life (HRQoL) to provide a health profile of the Jamaican haemophilia population. RESULTS: In all, 45 PWH were registered (mean age: 29, range: 0.17-69 years), including 13 children (<18 years of age) and 32 adults. In this sample, 41 had haemophilia A (30 severe) and 4 had haemophilia B (3 severe); 10 patients with haemophilia A were inhibitor positive. The results indicate that adults with haemophilia in Jamaica have significant joint damage: mean Haemophilia Joint Health Score (HJHS) = 42.1 (SD = 17.3); moderate activity levels - mean Haemophilia Activities List (HAL) score = 64.8 (SD = 17.8); and low HRQoL scores - mean Haemo-QoL-A score = 62.3 (SD = 19.4). Results for children are also reported but should be interpreted with caution due to the small sample size. CONCLUSIONS: There is a very high burden of disease in PWH in Jamaica. The health profiles reported in this paper are an essential first step in advocating for a multidisciplinary Comprehensive Care Program for assessment and care of PWH in Jamaica.

Variation in the distribution of large-scale spatiotemporal patterns of activity across brain states.

A few large-scale spatiotemporal patterns of brain activity (quasiperiodic patterns or QPPs) account for most of the spatial structure observed in resting state functional magnetic resonance imaging (rs-fMRI). The QPPs capture well-known features such as the evolution of the global signal and the alternating dominance of the default mode and task positive networks. These widespread patterns of activity have plausible ties to neuromodulatory input that mediates changes in nonlocalized processes, including arousal and attention. To determine whether QPPs exhibit variations across brain conditions, the relative magnitude and distribution of the three strongest QPPs were examined in two scenarios. First, in data from the Human Connectome Project, the relative incidence and magnitude of the QPPs was examined over the course of the scan, under the hypothesis that increasing drowsiness would shift the expression of the QPPs over time. Second, using rs-fMRI in rats obtained with a novel approach that minimizes noise, the relative incidence and magnitude of the QPPs was examined under three different anesthetic conditions expected to create distinct types of brain activity. The results indicate that both the distribution of QPPs and their magnitude changes with brain state, evidence of the sensitivity of these large-scale patterns to widespread changes linked to alterations in brain conditions.

Variation in the Distribution of Large-scale Spatiotemporal Patterns of Activity Across Brain States.

A few large-scale spatiotemporal patterns of brain activity (quasiperiodic patterns or QPPs) account for most of the spatial structure observed in resting state functional magnetic resonance imaging (rs-fMRI). The QPPs capture well-known features such as the evolution of the global signal and the alternating dominance of the default mode and task positive networks. These widespread patterns of activity have plausible ties to neuromodulatory input that mediates changes in nonlocalized processes, including arousal and attention. To determine whether QPPs exhibit variations across brain conditions, the relative magnitude and distribution of the three strongest QPPs were examined in two scenarios. First, in data from the Human Connectome Project, the relative incidence and magnitude of the QPPs was examined over the course of the scan, under the hypothesis that increasing drowsiness would shift the expression of the QPPs over time. Second, using rs-fMRI in rats obtained with a novel approach that minimizes noise, the relative incidence and magnitude of the QPPs was examined under three different anesthetic conditions expected to create distinct types of brain activity. The results indicate that both the distribution of QPPs and their magnitude changes with brain state, evidence of the sensitivity of these large-scale patterns to widespread changes linked to alterations in brain conditions.

Evolution of blood donation patterns in a hospital-based blood centre over a seven-year period: implications for donor recruitment and retention.

OBJECTIVE: The aim of this study is to investigate the effect of a public appeal to encourage voluntary blood donation by comparing the pattern of blood donations in 2000 and 2007. METHODS: A retrospective analysis of blood donation records was conducted at the University Hospital of the West Indies (UHWI) Blood Collection Centre from April to December of 2000 and 2007. Data were analysed to identify any significant changes in donation patterns and donor profiles. RESULTS: The total number of blood donor records reviewed was 3194 in 2000 and 2634 in 2007 representing 69.0% and 72.3% of the total blood donations, respectively. Autologous donations accounted for 1% in 2000 and 2.2% in 2007; however, there was no corresponding change in voluntary donations (3.4% in 2000 and 3.2% in 2007). Despite a reduction in the number of first-time donors (1539 in 2000 and 1115 in 2007), the percentage of units discarded for the presence of a marker of transfusion transmission infection (TTI) increased, being 6.5% in 2000 and 7.4% in 2007. Human T-lymphotropic virus (HTLV) was the most common infectious marker in 2000 (3.4% of donors) whereas reactive Venereal Disease Research Laboratory (VDRL) predominated in 2007 (3.6% of donors). CONCLUSION: The per capita donations (0.99% in 2000 and 0.88% in 2007) failed to meet the World Health Organization (WHO) recommendation for an adequate blood supply of 1-3%. Despite a national effort to improve voluntary donations, the positive changes in the pattern of blood donation over a period of seven years were limited to a decrease in the proportion of first-time donors and an increase in blood donors with one to four previous donations.

Chronic myeloid leukaemia at the University Hospital of the West Indies: a 17-year review.

OBJECTIVE: To determine the presenting features and evolution of patients diagnosed with chronic myeloid leukaemia between 1983 and 1999 at the University Hospital of the West Indies. METHODS: Forty-one records were retrospectively analyzed for the patients' demographics, reasons for referral, clinical features, laboratory investigations and the time to blast transformation and death. RESULTS: Seventy-one per cent were males and 29% were females. The male to female ratio was 2.4:1. The median age at presentation was 37 years (range 14-81 years). Seventy-eight per cent of the patients presented in the chronic phase. Weight loss and splenomegaly were the most frequent presenting features being seen in 54 and 83 per cent respectively. The median survival was 36 months. CONCLUSION: In this study, the clinical features and evolution were comparable to existing data. Improved accrual and routine Philadelphia chromosome testing would provide a more accurate reflection of the status of CML in our population.

Synthesis and antitumor activity of new glycosides of epipodophyllotoxin, analogues of etoposide, and NK 611.

A series of 3-amino- and 3-alkylamino-2-deoxy-beta-D-ribo- and beta-D-arabino-glycosides of 4'-demethylepipodophyllotoxin have been synthesized by means of an improved trimethylsilyliodide procedure for the podophyllotoxin-4'-demethylepipodophyllotoxin conversion, an efficient and high yielding synthesis of silyl glycoside donors of 3-azido-2,3-dideoxy-beta-D-ribo- and beta-D-arabino-hexopyranosides and stereoselective glycosylations. In vitro evaluation of cytotoxic effects against murine L1210 leukemia critically demonstrates the essential role played by a 4,6-acetal for biological activity. Among the most cytotoxic compounds, 3-amino-2,3-dideoxy- and 3-N, N-(dimethylamino)-2,3-dideoxy etoposide analogues, 17 and 27-29 are at least as potent as etoposide on the in vivo P388 (iv/ip) murine leukemia models. However, surprisingly enough, none of these compounds inhibits the human DNA topoisomerases I or II or binds to tubulin to prevent its polymerization and microtubule assembly. Therefore, their mechanism of action remains to be cleared up.

Inhibitory activity of the new adamantane derivative N,N'-bis(ethylene)-P(1-adamantyl)-phosphonic diamide against Rous sarcoma virus.

A new adamantane derivative N,N'-bis (ethylene)P(1-adamantyl)-phosphonis diamide, was found to inhibit Rous sarcoma virus replication in much the same manner as reported for the parent compound, 1-adamantanamine hydrochloride.

Relations among joint attention, amount of intervention and language gain in autism.

The purpose of the present study was to investigate the unconditional and conditional relations between amount of intervention and language development in children with autism. Joint attention skills were proposed as child characteristics that might moderate this relation. The results replicated previous findings that better joint attention skills were associated with greater language development. The results further indicated that the relation between amount of intervention and gain in language age was conditional; it depended upon the child's ability to respond to bids for joint attention from others and initial language skills. The current study demonstrated the utility of employing characteristics of children as moderators of relations between interventions and developmental outcomes.

A tethering system for intravenous and intragastric drug administration in the baboon.

A system for minimally restraining adult baboons with chronic intravenous (IV) or intragastric (IG) catheters for long term pharmacological and behavioral studies is described. The system consists of an adjustable foam-padded backplate and harness which is custom-fitted to each animal. A flexible stainless-steel cable connects the backplate to a liquid swivel through which the drugs are administered. Methods for the preparation and surgical implantation of IV and IG catheters are also described. Intravenous catheters were sequentially implanted in the internal jugular, femoral, axillary and external jugular veins. Catheters have remained patent for as long as 45 months, and catheter life appears to be conjointly determined by both site and number of successive implantations. The advantages of the harness/tether system over previously used chair-restraint procedures include greater freedom of movement, fewer restraint-related health problems, and longer experimental life of the animals.

The role of a clinical outcome research evaluator. A graduate nursing student's experience.

Outcome evaluation research is a relatively new paradigm that allows those in nursing to explain the impact of an intervention. The term efficacy is used when an intervention is evaluated as part of a controlled research study, while effectiveness denotes outcome evaluation of uncontrolled interventions in diverse settings. This article describes a graduate nursing student's supervised research experience that contributed to evaluating the efficacy of an intervention consisting of counseling caregivers of elders with dementia via telecommunications. The student's preparation for the role of research evaluator included acquisition of conceptual knowledge about evaluation research, interviewing techniques, and analytical skills to interpret evaluation data. Conceptual knowledge focused on the application of the Donabedian Structure. Process, Outcome Model and issues such as stakeholder, vested interest, and confidentiality. Data collection interviews involved the use of open-ended questions (qualitative) and administration of a structured questionnaire (quantitative). Analysis of qualitative data required identification of positive and negative themes; item responses on the structured questionnaire were compiled as percentages. Findings from the evaluation were used to improve the design of an ongoing intervention study.

Audit of pressure area care and documentation.

Intensive care patients are at particular risk of pressure damage. Documentation does not always fully reflect practice. Pressure sore identification remains a subjective issue. Nurses do not always complete patient documentation.

Effector functions of camelid heavy-chain antibodies in immunity to West Nile virus.

Three classes of IgG have been described for camelids. IgG1 has a conventional four-chain structure, while IgG2 and IgG3 do not incorporate light chains. The structures and antigen-binding affinities of the so-called heavy-chain classes have been studied in detail; however, their regulation and effector functions are largely undefined. The aim of this study was to examine the participation of conventional and heavy-chain IgG antibodies in the camelid immune defense directed against West Nile virus (WNV). We found that natural infection or vaccination with killed WNV induced IgG1 and IgG3. Vaccination also induced IgG1 and IgG3; IgG2 was produced during the anamnestic response to vaccination. When purified IgGs were tested in plaque-reduction neutralization titer (PRNT) tests, IgG3 demonstrated PRNT activities comparable to those of conventional IgG1. In contrast, IgG2 demonstrated only suboptimal activity at the highest concentrations tested. Flow cytometric analysis revealed that macrophages bound IgG1, IgG2, and IgG3. Furthermore, subneutralizing concentrations of all three isotypes enhanced WNV infection of cultured macrophages. Our results document distinctions in regulation and function between camelid heavy-chain isotypes. The reduced size and distinct structure of IgG3 did not negatively impact its capacity to neutralize virus. In contrast, IgG2 appeared to be less efficient in neutralization. This information advances our understanding of these unusual antibodies in ways that can be applied in the development of effective vaccines for camelids.

Application of monoclonal antibodies in functional and comparative investigations of heavy-chain immunoglobulins in new world camelids.

Of the three immunoglobulin G (IgG) isotypes described to occur in camelids, IgG2 and IgG3 are distinct in that they do not incorporate light chains. These heavy-chain antibodies (HCAbs) constitute approximately 50% of the IgG in llama serum and as much as 75% of the IgG in camel serum. We have produced isotype-specific mouse monoclonal antibodies (MAbs) in order to investigate the roles of HCAbs in camelid immunity. Seventeen stable hybridomas were cloned, and three MAbs that were specific for epitopes on the gamma chains of llama IgG1, IgG2, or IgG3 were characterized in detail. Affinity chromatography revealed that each MAb bound its isotype in solution in llama serum. The antibodies bound to the corresponding alpaca IgGs, to guanaco IgG1 and IgG2, and to camel IgG1. Interestingly, anti-IgG2 MAbs bound three heavy-chain species in llama serum, confirming the presence of three IgG2 subisotypes. Two IgG2 subisotypes were detected in alpaca and guanaco sera. The MAbs detected llama serum IgGs when they were bound to antigen in enzyme-linked immunosorbent assays and were used to discern among isotypes induced during infection with a parasitic nematode. Diseased animals, infected with Parelaphostrongylus tenuis, did not produce antigen-specific HCAbs; rather, they produced the conventional isotype, IgG1, exclusively. Our data document the utility of these MAbs in functional and physiologic investigations of the immune systems of New World camelids.

Arf family GTPases: roles in membrane traffic and microtubule dynamics.

Database mining and phylogenetic analysis of the Arf (ADP-ribosylation factor) superfamily revealed the presence in mammals of at least 22 members, including the six Arfs, two Sars and 14 Arl (Arf-like) proteins. At least six Arf family members were found in very early eukaryotes, including orthologues of Arf, Sar, Arl2, Arl3, Arl6 and Arl8. While roles for Arfs in membrane traffic are well known, those for most of the Arls remain unknown. Depletion in cells of the most closely related human Arf proteins, Arf1-Arf5, reveals specificities among their cellular roles and suggests that they may function in pairs at different steps in endocytic and secretory membrane traffic. In addition, recent results from a number of laboratories suggest that several of the Arl proteins may be involved in different aspects of microtubule-dependent functions. Thus, a second major role for Arf family GTPases, that of regulating microtubules, is emerging. Because membrane traffic is often dependent upon movement of vesicles along microtubules this raises the possibility that these two fundamental functions of Arf family members, regulation of vesicle traffic and microtubule dynamics, diverged from one function of Arfs in the earliest cells that has continued to branch and allow additional levels of regulation.

Light activation of ribulose bisphosphate carboxylase: purification and properties of the enzyme in tobacco.

The development of methods of preparation of long wavelength ultraviolet light capable of activating ribulose bisphosphate carboxylase is reported. This preparation was obtained from tobacco (Nicotiana tabacum) leaves which had reached about one-half maximum leaf weight. It was prepared at low ionic strength by use of mixed anion and cation exchange resins and buffers containing dimethylsulfoxide. The preparation is greatly enriched in fraction I protein to the point of apparent homogeneity. When assayed in the presence of saturating ribulose bisphosphate and sodium bicarbonate, the rate of carbon fixation is a linear function of long wavelength ultraviolet irradiation in the range of 20,000 to 30,000 ergs per square centimeter per second. Glutathione (5 mm) inhibits light activation without affecting activity in the dark. Copper sulfate inhibits both light and dark activity, but is slightly less effective in the presence of ultraviolet light. Sucrose inhibition of carboxylation is only readily apparent in the absence of ultraviolet light. Ammonium sulfate precipitation followed by solubilization in buffers containing dimethylsulfoxide plus heat treatment promotes ultraviolet light activation.

Phosphoserine and phosphohydroxypyruvic Acid: evidence for their role as early intermediates in photosynthesis.

Photosynthetic fixation of (14)CO(2) in the bean Phaseolus vulgaris, cv. Pencil Pod Black Wax, resulted in the appearance of labeled compounds that were characterized as phosphoserine and phosphohydroxypyruvate by chromatographic separation and by the synthesis of chemical derivatives. In (14)CO(2)/(12)CO(2) pulse-chase experiments these metabolites demonstrated the rapid pool saturation and depletion of (14)C characteristic of early intermediates in photosynthetic carbon fixation. They were present in sufficient amounts to account for about 35% of total carbon fixed in 1 minute.

Differences between Fragaria clones by fourth derivative room temperature spectroscopy of intact leaves.

Clones of Fragaria were characterized by the attenuance (absorption) spectra of their photosynthetic apparatus. This method uses fourth derivative analysis of spectra of intact lamina of detached leaves at room temperature (20-25 C). Twenty-one different species and hybrids of Fragaria were examined. F. chiloensis accessions frequently have characteristic fourth derivative spectra distinct from that of other Fragaria species. These spectra are characterized by a strong band that appears to be photosystem I component Ca 693; and is correlated with a higher chlorophyll b content per unit area of leaf, and a lower chlorophyll a/b ratio.