Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 112
Filter
1.
J Relig Health ; 62(3): 2196-2212, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36242707

ABSTRACT

Violence, abuse and neglect constitute major threats to children's health and wellbeing globally. However, until recently, relatively little systematic attention has been paid to the role of faith communities in shaping the protective environment for children. This paper describes the development of a measure to capture child-protective disposition amongst faith communities through field studies with faith leaders and their spouses in Senegal, Uganda and Guatemala. Identifying common factors related to child care and protection practices, orientation to child rights and approaches to discipline, the measure potentially serves to both inform and evaluate interventions seeking to engage with the beliefs and behaviours of faith communities to support children's health and wellbeing.


Subject(s)
Child Abuse , Spouses , Humans , Child , Uganda , Guatemala , Senegal , Child Abuse/prevention & control
2.
Soc Sci Med ; 220: 22-30, 2019 01.
Article in English | MEDLINE | ID: mdl-30390471

ABSTRACT

Resilience is increasingly recognised as a key process mitigating the impact of shocks and stressors on functioning. The literature on individual and community resilience is being extended to address characteristics of resilient service delivery systems in contexts of adversity. The validity and utility of a capacity-oriented resilience framework (including absorption, adaptation and transformation) is examined with respect to the functioning of United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) health systems in Lebanon and Jordan in the context of the Syrian crisis. We completed 62 semi-structured interviews (30 in Lebanon in November-December 2016, and 32 in Jordan in January 2017) with professionals at primary care, area, and country management levels. Participants reflected on changes in population health status and health service delivery during the Syrian crisis, notably with respect to the influx of refugees from Syria. Interviews were analysed through inductive thematic analysis and used to critically interrogate health systems resilience against a pro-capacities framework. We find that UNRWA systems in Lebanon and Jordan were broadly resilient, deploying diverse strategies to address health challenges and friction between host and refugee populations. Absorptive capacity was evidenced by successful accommodation of increased patient numbers across most service areas. Adaptive capacities were reflected in broadening of collaboration and reconfiguration of staff roles to enhance service delivery. Transformative capacities were demonstrated in the revision of the service packages provided. While manifest as technical capacities, these clearly drew upon solidarity and commitment linked to the political context of the Palestinian experience. The study adds to the limited literature on health system and organizational resilience and indicates that capacity-oriented framings of resilience are valuable in extracting generalizable lessons for health systems facing adversity. The proposed resilience framework promises to guide strategies for sustained care delivery in these contexts.


Subject(s)
Arabs , Delivery of Health Care/organization & administration , Health Services Needs and Demand/organization & administration , Refugees , Resilience, Psychological , Government Programs/organization & administration , Humans , Interviews as Topic , Jordan , Lebanon , Syria
3.
Mucosal Immunol ; 10(2): 361-372, 2017 03.
Article in English | MEDLINE | ID: mdl-27328989

ABSTRACT

Infections caused by bacteria in the airway preferentially induce a Th17 response. However, the mechanisms involved in the regulation of CD4 T-cell responses in the lungs are incompletely understood. Here, we have investigated the mechanisms involved in the regulation of Th17 differentiation in the lungs in response to immunization with lipopolysaccharide (LPS) as an adjuvant. Our data show that both Myd88 and TRIF are necessary for Th17 induction. This distinctive fate determination can be accounted for by the pattern of inflammatory cytokines induced by airway administration of LPS. We identified the production of interleukin (IL)-1ß and IL-6 by small macrophages and IL-23 by alveolar dendritic cells (DCs), favoring Th17 responses, and IL-10 repressing interferon (IFN)-γ production. Furthermore, we show that exogenous IL-1ß can drastically alter Th1 responses driven by influenza and lymphocytic choriomeningitis virus infection models and induce IL-17 production. Thus, the precision of the lung immune responses to potential threats is orchestrated by the cytokine microenvironment, can be repolarized and targeted therapeutically by altering the cytokine milieu. These results indicate that how the development of Th17 responses in the lung is regulated by the cytokines produced by lung DCs and macrophages in response to intranasal immunization with LPS adjuvant.


Subject(s)
Adaptor Proteins, Vesicular Transport/metabolism , Influenza A Virus, H1N1 Subtype/immunology , Lung/metabolism , Lymphocytic Choriomeningitis/immunology , Lymphocytic choriomeningitis virus/immunology , Myeloid Differentiation Factor 88/metabolism , Orthomyxoviridae Infections/immunology , Th17 Cells/immunology , Adaptor Proteins, Vesicular Transport/genetics , Administration, Intranasal , Animals , Cell Differentiation , Cells, Cultured , Cellular Microenvironment , Cytokines/metabolism , Immunization , Lipopolysaccharides/immunology , Lung/pathology , Lymphocyte Activation , Mice , Mice, Inbred C57BL , Mice, Knockout , Myeloid Differentiation Factor 88/genetics
4.
Science ; 345(6202): 1290-2, 2014 Sep 12.
Article in English | MEDLINE | ID: mdl-25214616

ABSTRACT

Given the growing scale and complexity of responses to humanitarian crises, it is important to develop a stronger evidence base for health interventions in such contexts. Humanitarian crises present unique challenges to rigorous and effective research, but there are substantial opportunities for scientific advance. Studies need to focus where the translation of evidence from noncrisis scenarios is not viable and on ethical ways of determining what happens in the absence of an intervention. Robust methodologies suited to crisis settings have to be developed and used to assess interventions with potential for delivery at scale. Strengthening research capacity in the low- to middle-income countries that are vulnerable to crises is also crucial.


Subject(s)
Disasters , Ethnic Violence , Evidence-Based Practice/methods , Delivery of Health Care , Humans
5.
J Appl Microbiol ; 110(6): 1571-83, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21447014

ABSTRACT

AIMS: Research into the relationship between pathogens, faecal indicator microbes and environmental factors in beach sand has been limited, yet vital to the understanding of the microbial relationship between sand and the water column and to the improvement of criteria for better human health protection at beaches. The objectives of this study were to evaluate the presence and distribution of pathogens in various zones of beach sand (subtidal, intertidal and supratidal) and to assess their relationship with environmental parameters and indicator microbes at a non-point source subtropical marine beach. METHODS AND RESULTS: In this exploratory study in subtropical Miami (Florida, USA), beach sand samples were collected and analysed over the course of 6 days for several pathogens, microbial source tracking markers and indicator microbes. An inverse correlation between moisture content and most indicator microbes was found. Significant associations were identified between some indicator microbes and pathogens (such as nematode larvae and yeasts in the genus Candida), which are from classes of microbes that are rarely evaluated in the context of recreational beach use. CONCLUSIONS: Results indicate that indicator microbes may predict the presence of some of the pathogens, in particular helminthes, yeasts and the bacterial pathogen Staphylococcus aureus including methicillin-resistant forms. Indicator microbes may thus be useful for monitoring beach sand and water quality at non-point source beaches. SIGNIFICANCE AND IMPACT OF THE STUDY: The presence of both indicator microbes and pathogens in beach sand provides one possible explanation for human health effects reported at non-point sources beaches.


Subject(s)
Bacteria/isolation & purification , Bathing Beaches , Environmental Monitoring/methods , Helminths/isolation & purification , Water Microbiology , Yeasts/isolation & purification , Animals , Colony Count, Microbial , Florida , Seawater/microbiology , Seawater/parasitology , Silicon Dioxide/analysis
6.
J Epidemiol Community Health ; 64(12): 1056-61, 2010 Dec.
Article in English | MEDLINE | ID: mdl-19934172

ABSTRACT

BACKGROUND: Gender-based violence is viewed as a significant problem in conflict-affected regions throughout the world. However, humanitarian organizations typically have been unable to reliably estimate the incidence of rape, intimate partner violence and other forms of sexual abuse in such settings. Such estimates are required to inform programming in contexts such as northern Uganda. METHODS: We sought to establish incidence rates for gender-based violence in internally-displaced-persons camps in northern Uganda. The assessments involved a "neighbourhood methodology," in which adult female heads of household reported about their own, their sisters' and their neighbours' experiences. 299 households were selected for interview across four camps by using systematic random sampling. FINDINGS: Interviews were completed by 204 respondents (5 women having declined interview and 90 not having been successfully contacted). These respondents reported on themselves, a total of 268 sisters and 1206 neighbours. Reports with respect to these alternative populations produced estimates of overall incidence of intimate partner violence in the past year of 51.7% (95% CI 44.8 to 58.7; respondents), 44.0% (95% CI 41.2 to 46.9; respondents' sisters) and 36.5% (95% CI 30.7 to 42.3; respondents' neighbours). In the same period, estimates of incidence of forced sex by husbands were 41.0% (95% CI 34.2% to 47.8%), 22.1% (95% CI 17.0 to 27.2) and 25.1% (95% CI 22.5 to 27.6), respectively, with incidence of rape by a perpetrator other than an intimate partner estimated at 5.0% (95% CI 2.0% to 8.0%), 4.2% (95% CI 1.8 to 6.6) and 4.3% (95% CI 3.1 to 5.5), respectively. INTERPRETATION: Gender-based violence-particularly intimate partner violence-is commonplace in postconflict Uganda. The neighbourhood method provides a promising approach to estimating human right violations in humanitarian settings.


Subject(s)
Population Surveillance/methods , Violence/statistics & numerical data , Warfare , Adult , Family Relations , Female , Humans , Incidence , Interviews as Topic , Residence Characteristics , Sampling Studies , Sex Offenses/statistics & numerical data , Sexual Partners , Spouse Abuse/statistics & numerical data , Uganda/epidemiology
7.
Lancet ; 364(9450): 2058-67, 2004.
Article in English | MEDLINE | ID: mdl-15582064

ABSTRACT

Mental health is becoming a central issue for public health complex emergencies. In this review we present a culturally valid mental health action plan based on scientific evidence that is capable of addressing the mental health effects of complex emergencies. A mental health system of primary care providers, traditional healers, and relief workers, if properly trained and supported, can provide cost-effective, good mental health care. This plan emphasises the need for standardised approaches to the assessment, monitoring, and outcome of all related activities. Crucial to the improvement of outcomes during crises and the availability to future emergencies of lessons learned from earlier crises is the regular dissemination of the results achieved with the action plan. A research agenda is included that should, in time, fill knowledge gaps and reduce the negative mental health effects of complex emergencies.


Subject(s)
Disasters , Mental Health Services , Refugees , Warfare , Depression/etiology , Depression/therapy , Emergencies , Health Services Research , Humans , Mental Health Services/organization & administration , Refugees/psychology , Stress Disorders, Post-Traumatic/etiology , Stress Disorders, Post-Traumatic/therapy
8.
Clin Exp Immunol ; 129(3): 519-26, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12197894

ABSTRACT

Epidermal Langerhans cells (LCs) play a pivotal role in the initiation of cutaneous immune responses. The maturation of LCs and their migration from the skin to the T cell areas of draining lymph nodes are essential for the delivery and presentation of antigen to naïve T cells. CD40, which acts as a costimulatory molecule, is present on LCs and the basal layer of keratinocytes in the skin. We show here that systemic treatment of mice with anti-CD40 antibody stimulates the migration of LCs out of the epidermis with a 70% reduction in LC numbers after 7 days, although changes in LC morphology are detectable as early as day 3. LC numbers in the epidermis returned to 90% of normal by day 21. As well as morphological changes, LC showed up-regulated levels of Class II and ICAM-1, with only minimal changes in CD86 expression 3 days following anti-CD40 treatment. Despite increased levels of Class II and ICAM-1, epidermal LC isolated from anti-CD40 treated mice were poor stimulators of a unidirectional allogeneic mixed leucocyte reaction (MLR), as were epidermal LC isolated from control mice. These results indicate that CD40 stimulation is an effective signal for LC migration, distinct from maturation of immunostimulatory function in the epidermis, which is not altered. These observations may have important implications for the mechanism of action of agonistic anti-CD40 antibodies, which have been used as an adjuvant in models of infection and experimental tumours and the primary immunodeficiency Hyper IgM syndrome caused by deficiency of CD40 ligand.


Subject(s)
Antibodies, Monoclonal/pharmacology , CD40 Antigens/immunology , Cell Movement , Langerhans Cells/immunology , Skin/immunology , Animals , Antibodies, Monoclonal/administration & dosage , Antigens, Surface/analysis , CD40 Antigens/genetics , Cell Count , Cells, Cultured , Epidermal Cells , Epidermis/immunology , Female , Immunophenotyping , Injections, Intraperitoneal , Langerhans Cells/cytology , Lymph Nodes/cytology , Lymph Nodes/immunology , Lymphocyte Culture Test, Mixed , Mice , Mice, Inbred BALB C , Mice, Inbred CBA , Mice, Knockout , Skin/cytology
9.
West Indian Med J ; 51(1): 25-7, 2002 Mar.
Article in English | MEDLINE | ID: mdl-12089870

ABSTRACT

Intestinal parasites contribute greatly to morbidity in developing countries. While there have been several studies of the problem in the Caribbean, including the implementation of control programmes, this has not been done for Guyana. The aim of this study was to determine the prevalence of intestinal parasites among young children in a town located in the interior of Guyana. Eighty-five children under the age of 12 years were studied prospectively for intestinal parasites in Mahdia, Guyana. Stool samples were transported in formalin to the Department of Microbiology, The University of the West Indies, Jamaica, for analysis using the formalin-ether concentration and Ziehl-Neelsen techniques. Data on age and gender of the children were recorded on field data sheets. At least one intestinal parasite was detected in 43.5% (37/85) of the children studied and multiple parasitic infections were recorded in 21.2% (18/85). The most common intestinal helminth parasite was hookworm (28.2%; 24/85), followed by Ascaris lumbricoides (18.8%; 16/85) and then Trichuris trichuria (14.1%; 12/85). Among the protozoan infections Giardia lamblia was detected in 10.5% (9/85) of the study population while Entamoeba histolytica appeared rarely. All stool samples were negative for Cryptosporidium and other intestinal Coccidia. There was no predilection for gender with any of the parasites. The pattern of distribution of worms in this area of Guyana was unlike that seen in other studies. Hookworm infection was the most common among the children and a large proportion had multiple infections. The study established the occurrence and prevalence of a number of intestinal parasites in the population of Guyana. This sets the stage for the design and implementation of more detailed epidemiological studies.


Subject(s)
Helminthiasis/epidemiology , Intestinal Diseases, Parasitic/epidemiology , Child , Child, Preschool , Feces/parasitology , Guyana/epidemiology , Humans , Infant , Pilot Projects , Prevalence , Prospective Studies
10.
West Indian med. j ; 51(1): 25-7, Mar. 2002. tab
Article in English | MedCarib | ID: med-101

ABSTRACT

Intestinal parasites contribute greately to morbidity in developing countries. While there have been several studies of the problem in the Caribbean, including the implementation of control programmes, this has not been done for Guyana. The aim of this study was to determine the prevalence of intestinal parasites among young children in a town located in the interior of Guyana. Eighty-five children under the age of 12 years were studied prospectively for intestinal parasites in Mahdia, Guyana. Stool samples were transported in formalin to the Department of microbiology, the University of the West Indies, Jamaica, for analysis using the formalin-ether concentration and Ziehl-Neelsen techniques. Data on age and gender of the children were recorded on field sheets. At least one intestinal parasite was detacted in 43.5 percent (37/85) of the children studied and multiple parasitic infections were recorded in 21.2 percent (18/85). The most common intestinal helminth parasite was hookworm (28.2 percent; 24/85), followed by Ascaris lumbricoides (18.8 percent; 16/85) and then Trichuris trichuria (14.1 percent; 12/85). Among the protozoan infections Giardia lamblia was detected in 10.5 percent (9/85) of the study population while Entamoeba histolytica appeared rarely. All stool samples were negative for Cryptosporidium and other intestinal Coccidia. There was no predilection for gender with any of the parasites. The pattern of distribution of worms in this area of Guyana was unlike that seen in other studies. Hookworm infection was the most common among the children and a large proportion had multiple infections. The study established the occurrence and prevalence of a number of intestinal parasites in the population of Guyana. This sets the stage for the design and implementation of more detailed epidemiological studies. (AU)


Subject(s)
Child , Child, Preschool , Female , Humans , Male , Intestinal Diseases, Parasitic/epidemiology , Cross-Sectional Studies , Guyana/epidemiology , Hookworm Infections/epidemiology , Ascaris lumbricoides/parasitology , Trichuris/parasitology , Giardia lamblia/parasitology , Helminths/parasitology
11.
West Indian med. j ; 51(1): 25-27, Mar. 2002.
Article in English | LILACS | ID: lil-333301

ABSTRACT

Intestinal parasites contribute greatly to morbidity in developing countries. While there have been several studies of the problem in the Caribbean, including the implementation of control programmes, this has not been done for Guyana. The aim of this study was to determine the prevalence of intestinal parasites among young children in a town located in the interior of Guyana. Eighty-five children under the age of 12 years were studied prospectively for intestinal parasites in Mahdia, Guyana. Stool samples were transported in formalin to the Department of Microbiology, The University of the West Indies, Jamaica, for analysis using the formalin-ether concentration and Ziehl-Neelsen techniques. Data on age and gender of the children were recorded on field data sheets. At least one intestinal parasite was detected in 43.5 (37/85) of the children studied and multiple parasitic infections were recorded in 21.2 (18/85). The most common intestinal helminth parasite was hookworm (28.2; 24/85), followed by Ascaris lumbricoides (18.8; 16/85) and then Trichuris trichuria (14.1; 12/85). Among the protozoan infections Giardia lamblia was detected in 10.5 (9/85) of the study population while Entamoeba histolytica appeared rarely. All stool samples were negative for Cryptosporidium and other intestinal Coccidia. There was no predilection for gender with any of the parasites. The pattern of distribution of worms in this area of Guyana was unlike that seen in other studies. Hookworm infection was the most common among the children and a large proportion had multiple infections. The study established the occurrence and prevalence of a number of intestinal parasites in the population of Guyana. This sets the stage for the design and implementation of more detailed epidemiological studies.


Subject(s)
Humans , Infant , Child, Preschool , Child , Intestinal Diseases, Parasitic/epidemiology , Helminthiasis/epidemiology , Pilot Projects , Prevalence , Prospective Studies , Feces , Guyana
12.
J Med Chem ; 44(23): 3925-31, 2001 Nov 08.
Article in English | MEDLINE | ID: mdl-11689078

ABSTRACT

A total of 34 analogues of the biguanide PS-15 (5s), a prodrug of the diaminotriazine WR-99210 (8s), have been prepared. Several of them, such as 5b (PS-33) and 5m (PS-26), maintain or exceed the in vivo activity of PS-15 while not requiring the use of highly regulated starting materials. The putative diaminotriazine metabolites of these new analogues (compounds 8) have also been prepared and shown to maintain the activity against resistant P. falciparum strains. The structure-activity relationships of biguanides 5 and putative metabolites 8 are discussed.


Subject(s)
Antimalarials/chemical synthesis , Folic Acid Antagonists/chemical synthesis , Guanidines/chemical synthesis , Prodrugs/chemical synthesis , Proguanil/analogs & derivatives , Proguanil/chemical synthesis , Tetrahydrofolate Dehydrogenase/metabolism , Triazines/chemical synthesis , Animals , Antimalarials/chemistry , Antimalarials/pharmacology , Antimalarials/toxicity , Drug Evaluation, Preclinical , Female , Folic Acid Antagonists/chemistry , Folic Acid Antagonists/pharmacology , Folic Acid Antagonists/toxicity , Guanidines/chemistry , Guanidines/pharmacology , Guanidines/toxicity , Malaria/drug therapy , Male , Mice , Plasmodium berghei , Plasmodium falciparum/drug effects , Prodrugs/chemistry , Prodrugs/pharmacology , Prodrugs/toxicity , Proguanil/chemistry , Proguanil/pharmacology , Proguanil/toxicity , Structure-Activity Relationship , Triazines/chemistry , Triazines/pharmacology , Triazines/toxicity
13.
Blood ; 98(3): 688-95, 2001 Aug 01.
Article in English | MEDLINE | ID: mdl-11468168

ABSTRACT

The migration of lymphocytes from the bloodstream into lymph nodes (LNs) via high endothelial venules (HEVs) is a prerequisite for the detection of processed antigen on mature dendritic cells and the initiation of immune responses. The capture and arrest of lymphocytes from flowing blood is mediated by the multistep adhesion cascade, but the mechanisms that lymphocytes use to penetrate the endothelial lining and the basement membrane of HEVs are poorly understood. Matrix metalloproteinases (MMPs) control the metastatic spread of tumor cells by regulating the penetration blood vessel basement membranes. In this study, synthetic and natural inhibitors were used to determine the role of MMPs and MMP-related enzymes in regulating lymphocyte extravasation in mice. Mice were treated systemically with the hydroxamate-based MMP inhibitor Ro 31-9790 and plasma monitored for effective levels of Ro 31-9790, which block shedding of L-selectin. The total numbers of lymphocytes recruited into LNs were not altered, but L-selectin levels were higher in mice treated with Ro 31-9790. A reduced number of lymphocytes completed diapedesis and there was an increase in the number of lymphocytes in the endothelial cell lining, rather than the lumen or the basement membrane of HEVs. Lymphocyte migration and L-selectin expression in the spleen were not altered by Ro 31-9790 treatment. Two MMP inhibitors, TIMP1 and Ro 32-1541, did not block L-selectin shedding and had no effect on lymphocyte migration across HEVs. These results suggest that metalloproteinase activity is required for lymphocyte transmigration across HEVs into LNs and provide evidence for the concept that metalloproteinases are important players in some forms of transendothelial migration. (Blood. 2001;98:688-695)


Subject(s)
Cell Movement/drug effects , Endothelium, Vascular/metabolism , Lymphatic System , Lymphocytes/cytology , Metalloendopeptidases/pharmacology , Animals , Enzyme Inhibitors/pharmacology , L-Selectin/metabolism , Lymph Nodes/blood supply , Lymphocytes/metabolism , Lymphocytes/physiology , Metalloendopeptidases/antagonists & inhibitors , Mice , Spleen/blood supply , Tissue Inhibitor of Metalloproteinases/pharmacology
14.
J Med Chem ; 43(14): 2753-8, 2000 Jul 13.
Article in English | MEDLINE | ID: mdl-10893313

ABSTRACT

Sixteen alkyl-substituted dispiro-1,2,4,5-tetraoxanes (7,8,15, 16-tetraoxadispiro[5.2.5.2]hexadecanes) were synthesized to explore dispiro-1,2,4,5-tetraoxane SAR and to identify tetraoxanes with better oral antimalarial activity than prototype tetraoxane 1 (WR 148999). The tetraoxanes were prepared either by peroxidation of the corresponding cyclohexanone derivatives in H(2)SO(4)/CH(3)CN or by ozonolysis of the corresponding cyclohexanone methyl oximes. Those tetraoxanes with alkyl substituents at the 1 and 10 positions were formed as single stereoisomers, whereas the five tetraoxanes formed without the stereochemical control provided by alkyl groups at the 1 and 10 positions were isolated as mixtures of diastereomers. Three of the sixteen tetraoxanes were inactive (IC(50)'s > 1000 nM), but five (2, 6, 10, 11, 12) had IC(50)'s between 10 and 30 nM against the chloroquine-sensitive D6 and chloroquine-resistant W2 clones of Plasmodium falciparum compared to corresponding IC(50)'s of 55 and 32 nM for 1 and 8.4 and 7.3 nM for artemisinin. We suggest that tetraoxanes 13, 16, and 17 were inactive and tetraoxanes 4 and 7 were weakly active due to steric effects preventing or hindering peroxide bond access to parasite heme. Tetraoxanes 1, 10, 11, and 14, along with artemisinin and arteether as controls, were administered po b.i.d. (128 mg/kg/day) to P. berghei-infected mice on days 3, 4, and 5 post-infection. At this dose, tetraoxanes 10, 11, and 14 cured between 40% and 60% of the infected animals. In comparison, artemisinin and tetraoxane 1 produced no cures, whereas arteether cured 100% of the infected animals. There was no apparent relationship between tetraoxane structure and in vitro neurotoxicity, nor was there any correlation between antimalarial activity and neurotoxicity for these seventeen tetraoxanes.


Subject(s)
Alkanes/chemical synthesis , Antimalarials/chemical synthesis , Spiro Compounds/chemical synthesis , Alkanes/chemistry , Alkanes/pharmacology , Alkanes/toxicity , Animals , Antimalarials/chemistry , Antimalarials/pharmacology , Antimalarials/toxicity , Malaria/drug therapy , Malaria/parasitology , Mice , Neurites/drug effects , Neuroblastoma , Plasmodium berghei , Plasmodium falciparum/drug effects , Spiro Compounds/chemistry , Spiro Compounds/pharmacology , Spiro Compounds/toxicity , Structure-Activity Relationship , Tumor Cells, Cultured
15.
Int Immunol ; 12(3): 241-51, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10700459

ABSTRACT

Several cell adhesion molecules that mediate the binding of lymphocytes to high endothelial venules (HEV) from flowing blood have been identified but the regulation of lymphocyte migration across the HEV wall into the lymph node (LN) is far from understood. In this study we have used an in vitro model of lymphocyte migration across HEV, and analysed the roles of two integrins in the binding and transendothelial migration of T lymphocytes and T lymphoblasts. The adhesion of T lymphocytes to high endothelial cells (HEC) cultured from rat LN HEV differed from that of T lymphoblasts since the percentage of T lymphoblasts that adhered and transmigrated was higher and was not increased by IFN-gamma pretreatment of HEC. Antibodies to alpha(4) integrins, VCAM-1 or LFA-1 maximally inhibited T lymphocyte adhesion by 40-50%, whereas antibodies to ICAM-1 were less effective (<20% inhibition). The effects of alpha(4) integrin and LFA-1 antibodies were additive, giving >90% inhibition. T lymphocytes which adhered in the presence of LFA-1 antibody showed reduced levels of transmigration and, in the presence of alpha(4) integrin antibody, slightly increased transmigration. Antibodies to alpha(4) integrins, VCAM-1, LFA-1 or ICAM-1 had little effect on T lymphoblast adhesion (maxima of 10-30% inhibition) and T lymphoblasts transmigrated normally in the presence of either alpha(4) integrin or LFA-1 antibodies. However, the effects of alpha(4) integrin and LFA-1 antibodies on T lymphoblast adhesion were synergistic, giving >90% inhibition of adhesion. These results suggest that the majority of T lymphoblasts use either alpha(4) integrins or LFA-1 to bind and transmigrate HEV, and the roles of these integrins on activated T cells are overlapping and redundant. In contrast, either integrin supports half-maximal binding of unactivated T lymphocytes to the surface of HEV and LFA-1 makes a larger contribution than alpha(4) integrins to transendothelial migration.


Subject(s)
Antigens, CD/physiology , Endothelium, Vascular/cytology , Intercellular Adhesion Molecule-1/physiology , Lymphocyte Function-Associated Antigen-1/physiology , T-Lymphocytes/cytology , Vascular Cell Adhesion Molecule-1/physiology , Animals , Antibodies, Monoclonal/pharmacology , Antigens, CD/immunology , Cell Adhesion/drug effects , Cells, Cultured , Endothelium, Vascular/metabolism , Humans , Integrin alpha4 , Intercellular Adhesion Molecule-1/immunology , Lymph Nodes/cytology , Lymphocyte Function-Associated Antigen-1/immunology , Rats , Rats, Inbred Strains , Recombinant Fusion Proteins/metabolism , Specific Pathogen-Free Organisms , T-Lymphocytes/metabolism , Vascular Cell Adhesion Molecule-1/genetics , Vascular Cell Adhesion Molecule-1/immunology , Venules
16.
Am J Trop Med Hyg ; 62(5): 573-8, 2000 May.
Article in English | MEDLINE | ID: mdl-11289666

ABSTRACT

The antimalarial peroxide, dispiro-1,2,4,5-tetraoxane WR 148999, was synergistic with chloroquine, quinine, mefloquine, and artemisinin against both D6 and W2 clones of Plasmodium falciparum. In consideration of the contrasting antagonism between artemisinin and chloroquine, these drug combination data imply that WR 148999 and artemisinin may not share a common mechanism of action. For Plasmodium berghei-infected mice given oral, subcutaneous, and intraperitoneal doses of WR 148999 ranging from 2 to 1024 mg/kg in the Thompson test, median survival times were 8.8, 11.8, and 27.5 days, respectively, compared to 8 days for control animals. Using subcutaneous administration, WR 148999 had a considerably longer duration of action than did artemisinin against P. berghei. WR 148999 did not significantly inhibit cytochrome P450 isozymes CYP 2C9, 2C19, 2D6, 2E1, or 3A4 (IC50 >500 microM) but did inhibit CYP 1A2 with an IC50 value of 36 microM, suggesting that WR 148999 may be metabolized by the latter CYP isozyme. These results combined with previous observations that formulation strategies and incorporation of polar functional groups in a series of WR 148999 analogs both failed to enhance tetraoxane oral antimalarial activity suggest that oral bioavailability of tetraoxane WR 148999 is more likely a function of extensive first-pass metabolism rather than solubility-limited dissolution.


Subject(s)
Antimalarials/therapeutic use , Artemisinins , Malaria/drug therapy , Plasmodium berghei/drug effects , Plasmodium falciparum/drug effects , Spiro Compounds/therapeutic use , Tetraoxanes , Animals , Antimalarials/pharmacology , Chloroquine/pharmacology , Chloroquine/therapeutic use , Cytochrome P-450 Enzyme Inhibitors , Drug Interactions , Drug Resistance , Drug Therapy, Combination , Erythrocytes/drug effects , Erythrocytes/parasitology , Humans , Lactones/therapeutic use , Malaria/parasitology , Malaria, Falciparum/parasitology , Mice , Sesquiterpenes/therapeutic use , Spiro Compounds/administration & dosage , Spiro Compounds/pharmacology
17.
Health Soc Care Community ; 8(6): 406-416, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11560711

ABSTRACT

This paper reports on variation in the cost and social outcomes of provision for clients with learning disabilities, resettled across different models of community accommodation; identifying personal and service-related characteristics influential on such variation. The study was conducted to inform the community reprovisioning strategy associated with the phased closure of the Gogarburn and Tornaveen learning disability hospitals in the Lothian region, Scotland. Total mean service costs, quality of life and community integration outcome data were collected and compared. Total mean service costs ranged between pound16 438 and pound74 097 per year (mean pound42 023; SD = pound16 712). Cost estimates varied by age and dependency group, with costs for elderly clients comparatively low. Overall, there was an inverse relationship between total mean costs and size of accommodation. There was no evidence of a direct relationship between costs and changes in social outcomes. Services with the lowest mean costs were, however, associated with the smallest increases in social outcomes. The most expensive services did not realise proportionally greater gains in social outcomes. The paper concludes that clients generally benefited from the transition from hospital to community accommodation. However, some experienced better outcomes than others. In the absence of a clear link between levels and type of resource use and social outcomes, it is difficult to identify which service features are more or less efficacious in achieving positive outcomes. Broader evaluation perspectives, embracing a fuller range of costs and benefits, will be required to unpack exactly what it is about different models of community care provision that leads to positive outcomes, or otherwise, for learning disability clients. A more sound evidence base is required before effective strategies can be designed to ensure that key policy outcomes are realised and social integration truly achieved.

18.
J Clin Microbiol ; 37(11): 3698-700, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10523577

ABSTRACT

Rapid detection of human immunodeficiency virus (HIV) infection can result in improved patient care and/or faster implementation of public health preventive measures. A new rapid test, Determine (Abbott, Abbott Park, Ill.), detects HIV type 1 (HIV-1) and HIV-2 antibodies within 15 min by using 50 microl of serum or plasma. No specialized equipment or ancillary supplies are required, and results are read visually. A positive result is noted by the appearance of a red line. An operational control (red line) indicates proper test performance. We evaluated the Determine rapid HIV detection test with a group of well-characterized serum samples (CD4 counts and viral loads were known) and serum samples from HIV-positive individuals at field sites in Honduras and the Dominican Republic. In the field evaluations, the results obtained by the Determine assay were compared to those obtained by local in-country HIV screening procedures. We evaluated serum from 100 HIV-positive patients and 66 HIV-negative patients. All samples gave the expected results. In a companion study, 42 HIV-positive samples from a Miami, Fla., serum bank were tested by the Determine assay. The samples had been characterized in terms of CD4 counts and viral loads. Fifteen patients had CD4 counts <200 cells/mm(3), while 27 patients had CD4 counts >200 cells/mm(3). Viral loads ranged from 630 to 873,746 log(10) copies/ml. All samples from the Miami serum bank were positive by the Determine test. Combined results from the multicenter studies indicated that the correct results were obtained by the Determine assay for 100% (142 of 142) of the HIV-positive serum samples and 100% (66 of 66) of the HIV-negative serum samples. The Determine test was simple to perform and the results were easy to interpret. The Determine test provides a valuable new method for the rapid identification of HIV-positive individuals, especially in developing countries with limited laboratory infrastructures.


Subject(s)
AIDS Serodiagnosis/methods , HIV Antibodies/blood , HIV Infections/diagnosis , Adult , CD4 Lymphocyte Count , Dominican Republic , Evaluation Studies as Topic , Female , Florida , HIV Infections/immunology , HIV-1/immunology , HIV-1/isolation & purification , HIV-2/immunology , HIV-2/isolation & purification , Honduras , Humans , Male , Middle Aged
20.
Lancet ; 354(9175): 304, 1999 Jul 24.
Article in English | MEDLINE | ID: mdl-10440312

ABSTRACT

There have been dramatic increases in dengue fever (DF) and dengue haemorrhagic fever in South America. Guyana has reported less than five cases per year for most of the past decade. We evaluated patients in a clinic in Georgetown, Guyana, over 2 days and found evidence of 50 cases of dengue infection.


PIP: This research letter evaluates the incidence of dengue fever and dengue hemorrhagic fever in Guyana, South America, in a study conducted at the Vector Control Medical Center on July 20-21, 1998. Venous blood samples were collected from 112 patients (99 men and 13 women ranging in age from 9 to 60 years) who were inflicted with fever, chills, malaise, and/or headache. 50 samples were detected to be dengue virus- positive, illustrating a 45% prevalence of recent dengue virus infection among the tested patients. This study revealed that the incidence of dengue fever in Guyana is under-reported. Thus, improvements should be made in the surveillance measures for dengue infection in Guyana and its surrounding countries.


Subject(s)
Dengue/epidemiology , Adolescent , Adult , Child , Female , Guyana/epidemiology , Humans , Male , Middle Aged , Seroepidemiologic Studies
SELECTION OF CITATIONS
SEARCH DETAIL
...