Integrating self-determination theory and the theory of planned behaviour to predict intention to donate blood.

OBJECTIVES: The aim of this research was to test a model integrating self-determination theory (SDT) and the theory of planned behaviour (TPB) to predict intention to donate blood. BACKGROUND: Social science research suggests that motivational orientations outlined by SDT can be usefully integrated with constructs from the TPB to collectively predict intention and behaviour. Such analysis has not yet been undertaken in the context of blood donation. METHODS: A total of 458 currently eligible donors completed measures of blood donor motivations, attitudes, subjective norms, perceived behavioural control (PBC) and intention. Path analyses modelled the direct and indirect effects (via TPB constructs) of motivational orientations on intention. RESULTS: SDT motivational orientations explained an additional 14% of the variance in blood donation intention, compared to a TPB-only model. Amotivation had a negative direct effect on intention; external regulation had no overall effect on intention; introjected regulation had positive direct and indirect effects on intention; and autonomous motivation predicted intention both directly as well as via attitudes, subjective norms and PBC. CONCLUSION: This research provides the first evidence that integrating SDT and the TPB is a useful approach in donor research, particularly for specifying plausible pathways through which motivational orientations impact intention to donate blood.

Anti-Blood Group Antibodies in Intravenous Immunoglobulin May Complicate Interpretation of Antibody Titers in ABO-Incompatible Transplantation.

Patients receiving ABO-incompatible (ABOi) kidney transplants are treated before and after transplant with combination therapy, such as intravenous immunoglobulin (IVIG) and therapeutic plasma exchange, to prevent allograft rejection by reducing anti-A and anti-B titers. Although generally considered safe, it is well known that commercial IVIG products contain detectable anti-A and anti-B, which can be associated with hemolysis. Different preparative manufacturing techniques during the production of IVIG affect ABO antibody levels in IVIG preparations; therefore, some manufacturers now use new methods to reduce anti-A/B levels at the preproduction stage. The variations in implementing these strategies creates the potential for significant variation in antibody titers between products and, in some cases, even between lots of the same IVIG product. We report a case of persistently elevated anti-A titers in an ABOi kidney transplant recipient associated with elevated ABO antibody titers present in the preparation of IVIG used at our facility.

Cryoprecipitate AHF vs. fibrinogen concentrates for fibrinogen replacement in acquired bleeding patients - an economic evaluation.

BACKGROUND: Fibrinogen repletion in patients with acquired bleeding disorders can be accomplished by transfusing cryoprecipitate AHF (cryo) or fibrinogen concentrate (FC); thus, we undertook an economic evaluation from the transfusion service perspective regarding the use of cryo vs. FC in patients with acquired bleeding. METHODS: We created a model comparing the cost of cryo vs. FC from the transfusion service perspective. A patient with acquired bleeding requiring fibrinogen replacement could receive either 15-20 cryo units or 3-4 g FC, consistent with the guidelines from the European Task Force for Advanced Bleeding Care in Trauma. All model parameters were estimated from institutional experiences and the medical literature. Additionally, a survey of US Transfusion Medicine fellowship directors was conducted. RESULTS: After adjusting for 28% wastage and technologist salary, cryo cost is $414/5-unit pool. Depending on the dose, FC is more expensive by $976-$1303. To be competitive with cryo, FC cost must decrease by 44% or be shown to save 0·25-0·66 ICU days. Of the 30 survey replies, 96·7% of US centres do not use FC for acquired bleeding with the top three reasons being cost (30%), off-label usage (27%) and insufficient evidence for usage (20%). Only 47% are willing to pay more for FC, with $437/g as the median amount. CONCLUSION: Fibrinogen concentrate is more expensive than cryo, even after adjusting for cryo wastage. To be economically competitive with cryo, FC must cost $414/g, or save on ICU length of stay, consistent with the survey's results.

Tau-crystallin/alpha-enolase: one gene encodes both an enzyme and a lens structural protein.

tau-Crystallin has been a major component of the cellular lenses of species throughout vertebrate evolution, from lamprey to birds. Immunofluorescence analysis of the embryonic turtle lens, using antiserum to lamprey tau-crystallin showed that the protein is expressed throughout embryogenesis and is present at high concentrations in all parts of the lens. Partial peptide sequence for the isolated turtle protein and deduced sequences for several lamprey peptides all revealed a close similarity to the glycolytic enzyme enolase (E.C. 4.2.1.11). A full-sized cDNA for putative duck tau-crystallin was obtained and sequenced, confirming the close relationship with alpha-enolase. Southern blot analysis showed that the duck genome contains a single alpha-enolase gene, while Northern blot analysis showed that the message for tau-crystallin/alpha-enolase is present in embryonic duck lens at 25 times the abundance found in liver. tau-Crystallin possesses enolase activity, but the activity is greatly reduced, probably because of age-related posttranslational modification. It thus appears that a highly conserved, important glycolytic enzyme has been used as a structural component of lens since the start of vertebrate evolution. Apparently the enzyme has not been recruited for its catalytic activity but for some distinct structural property. tau-Crystallin/alpha-enolase is an example of a multifunctional protein playing two very different roles in evolution but encoded by a single gene.

Further insight into the bovine serum albumin assay (the in vitro anti-inflammatory assay).

The present article reports on the comparative cost of using the Bovine Serum Albumin as an assay for detecting natural products with anti-inflammatory activities relative to the use of animals. This is an addendum to the West Indian Medical Journal article; 2008; 57(4); 327-31.

Implications of dibenzyl trisulphide for disease treatment based on its mode of action.

Studies conducted on the secondary metabolite (natural product), dibenzyl trisulphide (DTS), which was isolated from the sub-tropical shrub Petiveria alliacea (guinea hen weed, anamu) [Phytolaccaceae] have shown tremendous pharmaceutical promise as a drug prototype. This is now reflected in the development of the broad spectrum anti-cancer molecule, fluorapacin (bis(4-fluorobenzyl) trisulphide) which has an excellent safety profile. The mode of action elucidated for DTS is the mitogen activated protein extracellular regulated kinases 1 and 2 (MAPKinases ERK 1 and ERK 2). The MAPKinase signal transduction biochemical pathways are important in the regulation of a wide range of cellular processes which are important in disease establishment. These processes include: cancer cell proliferation, nerve repair, memory enhancement, autoimmune diseases, which are linked to thymic cell involution and bone marrow functions, cerebrovascular and cardiovascular diseases. In addition to the MAPkinase signal transduction mode of action, DTS also prevents the denaturation of serum albumin which is a feature of nonsteroidal anti-inflammatory drugs, thus supporting the molecule's possible role in the treatment of inflammatory ageing diseases.

The outcome of loop ileostomy closure: a prospective study.

BACKGROUND: The use of a loop ileostomy is an effective method to protect pelvic anastomoses, although there is some debate as to the routine use of a stoma. A second operation is required to close the stoma, with potential complications. OBJECTIVE: The aim of this study was to assess prospectively the morbidity of closure of loop ileostomy. METHOD: All patients scheduled for loop ileostomy closure over a 12-month period were included. The patient demographics, operative technique, complications and length of stay were recorded prospectively. RESULTS: Fifty consecutive patients (28 males and 22 females) with a median age (interquartile range, IQR) of 56 (42-73) years underwent closure of loop ileostomy, at a median time (IQR) of 29 (18-48) weeks after formation. Twelve patients (24%) developed complications: six (12%) had intestinal obstruction of which one required a laparotomy, four (8%) had wound infections of which one required re-operation, one (2%) had an ileal anastomotic leak and subsequently died and one (2%) died from a myocardial infarction. The median length (IQR) of hospital stay was 8 (7-10) days. CONCLUSION: We have demonstrated that a quarter of patients develop complications after loop ileostomy closure. The majority of these are minor. Methods to reduce the number of complications, such as optimum time for closure and distal limb irrigation techniques, need to be studied.

Passive immunity in Ontario dairy calves and investigation of its association with calf management practices.

Adequate passive transfer of maternal immunoglobulin is important for optimal health and performance in newborn dairy calves. From June to October 2003 and January to April 2004, blood samples were collected from 961 dairy calves 0 to 8 d of age on 11 farms in southwestern Ontario. This was followed by a second study conducted from May to October 2004, in which similar samples were taken from 422 calves up to 8 d of age on 119 dairy farms throughout southern Ontario. For each sample collected, serum refractometry was used to evaluate serum total protein (TP) as a measure of passive transfer of maternal immunity. During each study, producers were asked to provide information on calf management practices, including details of colostrum feeding. Data were analyzed to assess the levels of maternal immunity present in the calves, and to investigate whether these were associated with any calf management or colostrum feeding practices used on the farms. Serum TP readings ranged from 3.5 to 9.8 g/dL. Controlling for any effects of variation between farms, we found no statistically significant difference in serum TP levels, or risk of failure of passive transfer (FPT), between heifer and bull calves. The odds of FPT in calves on farms where more than 75% of cows were usually allowed to remain with their calves for more than 3 h after calving were significantly higher than the odds of FPT in calves on farms where dams and calves were separated within 3 h of the birth. Furthermore, an increased volume of colostrum given to calves within 6 h of birth was significantly associated with a reduced risk of FPT in calves. Information from this work provides valuable insight into the efficiency of passive transfer in newborn dairy calves in southern Ontario.

The in vitro anti-denaturation effects induced by natural products and non-steroidal compounds in heat treated (immunogenic) bovine serum albumin is proposed as a screening assay for the detection of anti-inflammatory compounds, without the use of animals, in the early stages of the drug discovery process.

There are emerging ethical issues with regards to the use of animals in the early stages of drug discovery for anti-inflammatory and degenerative diseases from natural products using the activity-directed isolation pathways when many compounds (eg > 100) are present in the crude extract or fraction and are to be tested The above-mentioned is the main reason for proposing the use of the in vitro anti-denaturation (stabilization) effects of heat treated (immunogenic) bovine serum albumin (BSA) as an assay. Current methods used for detecting and isolating a wide range of anti-inflammatory compounds in the early stages of the drug discovery process utilize a large number of animals. When BSA is heated and is undergoing denaturation, it expresses antigens associated to Type III hypersensitive reaction and which are related to diseases such as serum sickness, glomerulonephritis, rheumatoid arthritis and systemic lupus erythematosus. Thus, the assay that is being proposed should be applicable to the discovery of drugs for treating the above mentioned diseases and others, once the compounds stabilize the denaturation process.

A critical review of the therapeutic potential of dibenzyl trisulphide isolated from Petiveria alliacea L (guinea hen weed, anamu).

The data compiled in the present review on dibenzyl trisulphide (DTS) isolated from Petiveria alliacea L (the guinea hen weed or anamu) revealed that the compound and its derivatives could be of tremendous pharmaceutical interest. The mode of action elucidated for DTS revealed that it is a mitogen activated protein extracellular regulated kinases 1 and 2 (MAPKinases erk1 and erk 2) signal transduction molecule. Dibenzyl trisulphide caused hyper-phosphorylation of growth factor induced MAPKinases (erk 1 and erk 2) phosphorylation, a process critical for the improvement of long term memory, and is implicated in neuronal growth. Dibenzyl trisulphide and its derivatives exhibited potent anti-proliferation/cytotoxic activity on a wide range of cancer cell lines. The cytotoxic activity of DTS was increased by 70-1000 fold when bound to albumin in vitro. Dibenzyl trisulphide seems to have a cytokine switching mechanism in which it down regulates cytokines from the Type I helper cells (Th -1 cell) pathway which contained several pro-inflammatory cytokines and up-regulates those on the Type 2 helper cells (Th-2) pathway. The trisulphide up-regulates some reticuloendothelial system parameters eg granulocyte counts and increased thymic and Peyer's patches masses via cell proliferation processes which are known to be regulated via the MAPKinase signal transduction pathway. When the zygotes ofAsternia pectinifera (Starfish) were exposed to DTS at concentration of 10 mM, a dose lethal to all cancer cells tested, it was observed that the sensitive process of protein biosynthesis was not affected Similarly, the proliferation of the HOFA human fibroblast, a noncancerous cell line, was not severely affected by DTS at 8.9 microM over seven days, a concentration also lethal to most cancer cell lines tested The implications of the findings will be highlighted in the present review.

Immunological evidence supporting the use of extracts from Boehmeria jamaicensis Urb for treating the common cold and sinus infections.

Mixed lymphocyte responses assays were conducted at 25.0 and 250.0 microg/mL of the crude ethanolic extract of Boehmeria jamaicensis Urb (coded as BJE) using peripheral lymphocytes obtained from individuals suffering from the common cold after four days of infection and from healthy individuals (without the common cold infection). At a concentration of 25 ug/mL, gamma interferon (IFN-gamma) was increased by 24.03 fold and interleukin 4 (IL-4) by 1.71 fold for the cells obtained from individuals with the common cold (Group A). The extract suppressed IFN-gamma by 8.3% while IL-4 was stimulated by 9.90 fold from peripheral lymphocytes obtained from healthy individuals (Group B). Gamma interferon was suppressed at 250 microg/mL while IL-4 was elevated by 1.86 fold for cells obtained from individuals suffering from the common cold (Group A). In conclusion, BJE could have implications for the treatment of the common cold.

In vitro anti-proliferation/cytotoxic activity of epingaione and its derivatives on the human SH-SY5Y neuroblastoma and TE-671 sarcoma cells.

Epingaione (4-Methyl-1-(5-methyl-2, 3,4,5-tetrahydro-[2,3']bifuranyl-5-yl)-pentan-2-one) was isolated as one of the major lipophilic secondary metabolites from the leaves and stems of Bontia daphnoides L. The compound gave 79.24% and 50.83% anti-proliferation/cytotoxic activity on the human SH-SY5Y neuroblastoma and TE-671 sarcoma cells in vitro at 50 pg/mL, respectively. Epingaione was transformed into eleven derivatives under laboratory conditions using ethanol, some gave greater anti-proliferation/cytotoxic activity on the cancer cell lines tested. One of the derivatives (compound 2) with enhanced cytotoxic activity was elucidated as 5'-Ethoxy-5-methyl-5-(4-methyl-2-oxo-pentyl)-2,3,4,5-tetrahydro-5'H-[2,3']bifuranyl-2'-one. Both epingaione and compound 2 caused an accumulation of arrested or dead SH-SY5Y neuroblastoma in the m-phase of the cell cycle as revealed by the m-phase specific marker KE 67.

Challenges in Interpretation of Diagnostic Test Results in a Mumps Outbreak in a Highly Vaccinated Population.

In spite of a greatly reduced incidence rate due to vaccination, mumps outbreaks continue to occur in several areas of the world, sometimes in vaccinated populations. This article describes an outbreak in a highly vaccinated population in southwestern Ontario, Canada, and the challenges encountered in interpreting the results of diagnostic tests used in the outbreak. During the outbreak, patients were interviewed and classified according to the outbreak case definition, and specimens were collected for diagnostic testing according to Ontario guidelines. Twenty-seven individuals were classified as confirmed cases (n = 19) or suspect cases (n = 8) according to the case definition, only 9 of which were laboratory-confirmed cases: 7 confirmed by reverse transcriptase PCR (RT-PCR) and 2 by IgM serology. All 19 confirmed cases represented patients who were associated with secondary schools in the local area and had been vaccinated against mumps with one (n = 2) or two (n = 17) doses of the measles-mumps-rubella (MMR) vaccine. This is the first published report of an outbreak of mumps in Ontario in which all confirmed cases had been vaccinated against the disease. It highlights the limitations of and difficulties in interpreting current mumps diagnostic tests when used in vaccinated individuals.

Public Health Follow-up of Suspected Exposure to Echinococcus multilocularis in Southwestern Ontario.

In the 3 years since the first report of canine alveolar echinococcosis (AE) in Ontario, three additional cases have been diagnosed in the province. Of the four cases reported to date, three have had no known history of travel outside the province. It is possible that this development is an indication of previously unrecognized environmental contamination with Echinococcus multilocularis eggs in some areas of the province. If so, there is the potential for an emerging threat to human health. This article describes a local public health department's investigation of the possible exposure to E. multilocularis of a number of individuals who had had contact with the latest of the four cases of canine AE, and summarizes a comprehensive decision process that can be used by public health departments to assist in the follow-up of such exposures.

Human rabies exposures and postexposure prophylaxis in South Carolina, 1993-2002.

OBJECTIVES: South Carolina mandates reporting of animal bites and manages distribution of biologics for rabies postexposure prophylaxis (PEP). Incidence and epidemiologic characteristics of potential human rabies exposures and preventive treatment in South Carolina from 1993 through 2002 were examined to help assess the burden of PEP in the state and determine if the incidence of rabies exposures has changed over time. METHODS: Data on animal exposure investigations and PEP administration at the state and county level were examined, and the annual incidences of potential rabies exposures and human PEP courses were calculated. RESULTS: The incidence of animal exposures for which investigations were initiated was 297.9 per 100,000 population per year, and the incidence of PEP was 10.6 per 100,000 population per year. At the county level, the incidence of PEP appeared inversely correlated with the population density. Most courses of PEP were administered following exposures to domestic species, although these animals accounted for only a small proportion of rabid animals in the state. The annual PEP incidence was similar throughout the study period, but it was markedly higher than estimates from 1981 (< 5/100,000 population per year). CONCLUSIONS: The incidence of PEP in South Carolina is higher than previously thought, and these findings suggest that incidence extrapolations for other states and at the national level may be underestimated. An accurate estimation of the incidence of PEP and an understanding of rabies epidemiology is important at the state level to allow for better public health planning.

Disassembly of microtubules and inhibition of neurite outgrowth, neuroblastoma cell proliferation, and MAP kinase tyrosine dephosphorylation by dibenzyl trisulphide.

Dibenzyl trisulphide (DTS), a main lipophilic compound in Petiveria alliacea L. (Phytolaccaceae), was identified as one of the active immunomodulatory compounds in extracts of the plant. To learn more about its biological activities and molecular mechanisms, we conducted one-dimensional NMR interaction studies with bovine serum albumin (BSA) and tested DTS and related compounds in two well-established neuronal cell-and-tissue culture systems. We found that DTS preferentially binds to an aromatic region of BSA which is rich in tyrosyl residues. In SH-SY5Y neuroblastoma cells, DTS attenuates the dephosphorylation of tyrosyl residues of MAP kinase (erk1/erk2). In the same neuroblastoma cell line and in Wistar 38 human lung fibroblasts, DTS causes a reversible disassembly of microtubules, but it did not affect actin dynamics. Probably due to the disruption of the microtubule dynamics, DTS also inhibits neuroblastoma cell proliferation and neurite outgrowth from spinal cord explants. Related dibenzyl compounds with none, one, or two sulphur atoms were found to be significantly less effective. These data confirmed that the natural compound DTS has a diverse spectrum of biological properties, including cytostatic and neurotoxic actions in addition to immunomodulatory activities.

Programmed cell death without DNA fragmentation in the jimpy mouse: secreted factors can enhance survival.

Jimpy is one of many related mutations affecting the myelin proteolipid protein gene that causes severe hypomyelination in the central nervous system (CNS). Underlying the hypomyelination is a failure of oligodendrocytes (OLs) to differentiate, and the premature death of large numbers of OLs during the developmental period. Previous light and electron microscopic evidence suggested that jimpy OLs die in a manner consistent with programmed cell death. We have used TUNEL staining as a biochemical marker for apoptosis in conjunction with immunostaining for OL and myelin markers. At 13 - 14 days postnatal, a time when the number of dying OLs in jimpy CNS is increased more than five times normal, there are only modest increases (70% in spinal cord; 20% in cerebral cortex) in TUNEL labeled cells in mutant CNS tissues. The results in vitro are similar, and only a small per cent of TUNEL labeled cells have the antigenic phenotype of OLs. The discrepancy between numbers of dying and TUNEL labeled cells suggests either that most jimpy OLs do not undergo programmed cell death or that the biochemical pathways leading to their death do not involve DNA fragmentation which is detected by the TUNEL method. We also present evidence that jimpy OLs show increased survival and enhanced differentiation when they are grown in vitro in medium conditioned by cells lines which express products of the proteolipid protein gene. Cell lines expressing proteolipid protein and the alternatively spliced DM20 protein have differential effects on cell numbers and production of myelin-like membranes.

The incidence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: all patients, idiopathic patients, and patients with severe ADAMTS-13 deficiency.

BACKGROUND: Accurate estimates of the incidence of thrombotic thrombocytopenic purpura (TTP) are important to assess the resources required for current treatments as well as to anticipate the need to develop new treatments. Previous estimates have been indirect and have not reported data on patients with ADAMTS-13 deficiency. OBJECTIVE: To determine the incidence of patients with TTP-hemolytic uremic syndrome (HUS) in three categories: all patients with clinically suspected TTP-HUS, patients with idiopathic TTP-HUS, and patients with severe ADAMTS-13 deficiency. METHODS: Incidence rates were estimated from the Oklahoma TTP-HUS Registry, analyzing all 206 consecutive patients from January 1, 1996 to June 30, 2004 who were treated with plasma exchange for their initial episode of clinically suspected TTP-HUS. ADAMTS-13 activity was measured in 186 (90%) of the 206 patients. RESULTS: The age-sex-race standardized annual incidence rates were 11.29 x 10(6) (95% CI: 9.70-12.88) for all patients with clinically suspected TTP-HUS; 4.46 x 10(6) (95% CI: 3.43-5.50) for patients with idiopathic TTP-HUS; and 1.74 x 10(6) (95% CI: 1.06-2.41) for patients with severe ADAMTS-13 deficiency (<5% activity). In all three categories, the incidence rates were greater for women and for blacks. For patients with severe ADAMTS-13 deficiency, the age-sex standardized incidence rate ratio of blacks to non-blacks was 9.29 (95% CI: 4.33-19.93). CONCLUSIONS: Accurate incidence rate estimates for all patients with clinically suspected TTP-HUS, idiopathic TTP-HUS, and TTP associated with severe ADAMTS-13 deficiency have been determined. The greater incidence among women and blacks is comparable with their increased risk for other autoimmune disorders.

Identification and characterisation of human Junctional Adhesion Molecule (JAM).

It is widely believed that migrating immune cells utilise the intercellular junctions as routes of passage, and in doing so cause the transient disruption of junctional structures. Thus there is much interest in the molecules that have been identified at cell-cell contact points and their potential involvement in the control of leukocyte diapedesis. In this report we describe the human orthologue to Junctional Adhesion Molecule (JAM), a recently identified member of the immunoglobulin superfamily expressed at intercellular junctions (Martin-Padura et al., 1998). The human protein shares a highly conserved structure and sequence with the murine protein. However it is distinct in that it is constitutively expressed on circulating neutrophils, monocytes, platelets and lymphocyte subsets. This broad expression pattern is similar to another IgSF molecule, CD31, expressed at intercellular junctions, and may indicate further complexities in the control of leukocyte/ endothelial interactions.