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Carmen H Logie Moses Okumu Daniel Kibuuka Musoke Robert Hakiza Simon Mwima Peter Kyambadde Heather Abela Lesley Gittings Joshua Musinguzi Lawrence Mbuagbaw Stefan Baral 《Journal of the International AIDS Society》2021,24(3)
IntroductionHIV‐related risks may be exacerbated in humanitarian contexts. Uganda hosts 1.3 million refugees, of which 60% are aged under 18. There are knowledge gaps regarding HIV testing facilitators and barriers, including HIV and intersecting stigmas, among urban refugee youth. In response, we explored experiences and perspectives towards HIV testing strategies, including HIV self‐testing, with urban refugee youth in Kampala, Uganda.MethodsWe implemented a qualitative study with refugee cisgender youth aged 16 to 24 living in Kampala''s informal settlements from February‐April 2019. We conducted five focus groups with refugee youth, including two with adolescent boys and young men, two with adolescent girls and young women and one with female sex workers. We also conducted five key informant (KI) interviews with government, non‐government and community refugee agencies and HIV service providers. We conducted thematic analyses to understand HIV testing experiences, perspectives and recommendations.ResultsParticipants (n = 49) included young men (n = 17) and young women (n = 27) originally from the Democratic Republic of Congo [DRC] (n = 29), Rwanda (n = 11), Burundi (n = 3) and Sudan (n = 1), in addition to five KI (gender: n = 3 women, n = 2 men; country of origin: n = 2 Rwanda, n = 2 Uganda, n = 1 DRC). Participant narratives revealed stigma drivers included fear of HIV infection; misinformation that HIV is a “Ugandan disease”; and blame and shame for sexual activity. Stigma facilitators included legal precarity regarding sex work, same‐sex practices and immigration status, alongside healthcare mistreatment and confidentiality concerns. Stigma experiences were attributed to the social devaluation of intersecting identities (sex work, youth, refugees, sexual minorities, people living with HIV, women). Participants expressed high interest in HIV self‐testing. They recommended HIV self‐testing implementation strategies to be peer supported and expressed concerns regarding sexual‐ and gender‐based violence with partner testing.ConclusionsIntersecting stigma rooted in fear, misinformation, blame and shame, legal precarity and healthcare mistreatment constrain current HIV testing strategies with urban refugee youth. Findings align with the Health Stigma and Discrimination Framework that conceptualizes stigma drivers and facilitators that devalue intersecting health conditions and social identities. Findings can inform multi‐level strategies to foster enabling HIV testing environments with urban refugee youth, including tackling intersecting stigma and leveraging refugee youth peer support. 相似文献
35.
Mozafarinia Maryam Rajabiyazdi Fateme Brouillette Marie-Josee Fellows Lesley K. Mayo Nancy E. 《Quality of life research》2021,30(11):3199-3211
Quality of Life Research - (1) To develop a personalized health outcome profile as a feedback tool to improve self-management in people living with chronic conditions such as HIV and (2) to... 相似文献
36.
Deborah L. Scarcella Lesley J. Bryan-Lluka 《Naunyn-Schmiedeberg's archives of pharmacology》1995,351(5):491-499
The aim of this study was to investigate the deamination of dopamine in the intact pulmonary circulation of isolated lungs of the rat. The first part of the study showed that dopamine is not converted to noradrenaline by dopamine--hydroxylase (DBH) when dopamine is perfused through isolated lung preparations with monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) inhibited. Hence, it was not necessary to inhibit DBH in subsequent experiments.The metabolite profile for deamination of dopamine in the lungs was examined by determining whether MAO and semicarbazide-sensitive amine oxidases (SSAO) contribute to the deamination of dopamine (and noradrenaline), and by determining the activity of MAO (kMAO) for the metabolism of dopamine. Lungs were perfused with I nmol/l 3H-dopamine or 3H-noradrenaline with COMT inhibited and, in experiments to determine the contribution of SSAO to deamination, with MAO inhibited. Inhibition of MAO reduced the deamination of dopamine and noradrenaline by 99.8% and 98.6%, respectively, indicating that MAO, and not SSAO, was responsible for deamination of the catecholamines in the lungs. The kMAO value for deamination of dopamine was 3.89 min–1. Further experiments were carried out to determine the contributions of MAO-A and MAO-B to the deamination of dopamine in lungs perfused with 1 nmol/l 3H-dopamine and 100 nmol/1 lazabemide or 300 nmol/I Ro41-1049, respectively. The values of kMAO-A and kMAO-B were 3.05 min–1 and 0.626 min–1, respectively.It was concluded that, in rat lungs, MAO-A contributed 78–84% and MAO-B 16–22% to the total deamination of dopamine and SSAO had no significant role in its pulmonary metabolism. These relative contributions of MAO-A and MAO-B to the deamination of dopamine are very similar to those that have been determined previously for noradrenaline, but the rate constant for deamination of dopamine is 26-fold greater than that for noradrenaline in rat lungs.Abbreviations COMT
Catechol-O-methyltransferase
- DBH
Dopamine-\-hydroxylase
- DOPEG
3,4-dihydroxyphenylglycol
- DOMA
3,4-dihydroxyman delic acid
- DOPAC
3,4-dihydroxyphenylacetic acid
- DOPET
3,4-dihydroxphenylethanol
- ECS
Extracellular space
- Km
Michaelis or half-saturation constant
- kCOMT
Rate constant for O-methylation by COMT
- kdeam
Rate constant for total deamination
- kMAO
Rate constant for deamination by MAO
- MAO
Monoamine oxidase
- MB-COMT
Membrane-bound COMT
- SSAO
Semicarbazidesensitive amine oxidases
- S-COMT
Soluble COMT
- T/M
Tissue to medium concentration ratio of dopamine or noradrenaline
- Vmax
Maximal rate
- Vst - st
Steady-state rate of metabolite formation 相似文献
37.
Peter J Harris Siriphun Hiranyachattada Arianne M Antoine Lesley Walker Angela M Reilly Eveline Eitle 《Clinical and experimental pharmacology & physiology》1996,23(Z3):112-118
- 1 The effects of angiotensin II (AngII) on water and electrolyte transport are biphasic and dose-dependent, such that low concentrations (10?12 to 10?9 mol/L) stimulate reabsorption and high concentrations (10?7 to 10?6 mol/L) inhibit reabsorption. Similar dose-response relationships have been obtained for luminal and peritubular addition of AngII.
- 2 The cellular responses to AngII are mediated via AT1 receptors coupled via G-regulatory proteins to several possible signal transduction pathways. These include the inhibition of adenylyl cyclase, activation of phospholipases A2, C or D and Ca2+ release in response to inositol-1,4,5,-triphosphate or following Ca2+ channel opening induced by the arachidonic acid metabolite 5,6,-epoxy-eicosatrienoic acid. In the brush border membrane, transduction of the AngII signal involves phospholipase A2, but does not require second messengers.
- 3 Angiotensin II affects transepithelial sodium transport by modulation of Na+/H+ exchange at the luminal membrane and Na+/HCO3 cotransport, Na+/K+-ATPase activity and K+ conductance at the basolateral membrane.
- 4 Atrial natriuretic factor (ANF) does not appear to affect proximal tubular sodium transport directly, but acts via specific receptors on the basolateral and brush border membranes to raise intracellular cGMP levels and inhibit AngII-stimulated transport.
- 5 It is concluded that there is a receptor-mediated action of ANF on proximal tubule reabsorption acting via elevation of cGMP to inhibit AngII-stimulated sodium transport. This effect is exerted by peptides delivered at both luminal and peritubular sides of the epithelium and provides a basis for the modulation by ANF of proximal glomerulotubular balance. The evidence reviewed supports the concept that in the proximal tubule, AngII and ANF act antagonistically in their roles as regulators of extracellular fluid volume.
38.
Franco M. Muggia Kenneth K. Chan Christy Russell Nicoletta Colombo James L. Speyer Kishore Sehgal Susan Jeffers Joan Sorich Lawrence Leichman Uziel Beller E. Mark Beckman 《Cancer chemotherapy and pharmacology》1991,28(4):241-250
Summary Intraperitoneal (i.p.) 5-fluoro-2-deoxyuridine (Floxuridine, FUdR, FdUrd) was evaluated in a phase I study at a starting level of 500 mg given on 1 day in 2 I 1.5% dialysate. Escalations within patients were allowed every other cycle. A total of 23 patients (age, 32–78 years) received 108 treatment courses. Local tolerance at all dose levels was excellent, with no cases of drug-related peritonitis being observed. Nausea and vomiting increased in severity in relation to dose and was universal at >3,000 mg ×3 days. One patient each developed grade 1 mucositis as well as diarrhea at a dose of 3,000 mg×3 days and leukopenia and thrombocytopenia at 5,000 mg×3 days. Peritoneal fluid (PF) and plasma (PL) FdUrd profiles were monitored by an HPLC method in 13 subjects, with 7 being studied serially at 2–4 increment doses for up to 6 h. Profiles that exhibited apparent linear pharmacokinetics gave PF drug levels 2–4 logs higher than the PL counterparts, with the latter essentially declining in parallel to the former, indicating that the disposition of FdUrd from the peritoneal compartment is rate-determining. The mean terminal half-life for PF FdUrd was found to be 115 min and mean peritoneal clearance was 25 ml/min. The vast differences in drug levels and AUC found between the PF and the PL profiles suggests a high systemic clearance of FdUrd, which was confirmed in two patients receiving 2 g FdUrd by short i.v. infusion. A disproportionate increase in the plasma FdUrd levels and the corresponding AUC values was found with increasing dose, suggesting a disproportionate increase in the systemic partitioning of FdUrd when doses were escalated within a patient. Substantial levels of peritoneal 5-fluorouracil (FUra) were also detected in most of the subjects. Thus, FdUrd was found to have several desirable properties for i.p. administration: (1) a 2- to 4-log pharmacologic advantage, (2) the absence of local toxicities, and (3) a favorable antitumor spectrum and some evidence of antitumor effects in this phase I and pharmacology study. A 3,000-mg dose given in 2 l 1.5% dialysate for 3 consecutive days exhibited antitumor activity and produced no systemic toxicity except nausea and vomiting, which was controlled by antiemetics. This dose schedule is therefore recommended for phase II trials directed against small-volume disease in the peritoneal cavity, such as may be found in some stages of ovarian and gastrointestinal cancers. In addition, it is suitable for further exploration as a part of regimens including systemic therapy or drugs that modulate the action of fluoropyrimidines.Supported in part by Cancer Center Core Grant CA 14089, by ROI CA 50 412, by an ACS Institutional Grant (IN21Z, to C. R.) and by the Italian-American Foundation award (to N. C.)Deceased 相似文献
39.
In vivo assessment of antiangiogenic activity of SU6668 in an experimental colon carcinoma model. 总被引:10,自引:0,他引:10
Pasquina Marzola Anna Degrassi Laura Calderan Paolo Farace Caterina Crescimanno Elena Nicolato Anna Giusti Enrico Pesenti Andrea Terron Andrea Sbarbati Tinya Abrams Lesley Murray Francesco Osculati 《Clinical cancer research》2004,10(2):739-750
PURPOSE: The purpose of this research was to assess in vivo by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) the antiangiogenic effect of SU6668, an oral, small molecule inhibitor of the angiogenic receptor tyrosine kinases vascular endothelial growth factor receptor 2 (Flk-1/KDR), platelet-derived growth factor receptor, and fibroblast growth factor receptor 1. EXPERIMENTAL DESIGN: A s.c. tumor model of HT29 human colon carcinoma in athymic mice was used. DCE-MRI with a macromolecular contrast agent was used to measure transendothelial permeability and fractional plasma volume, accepted surrogate markers of tumor angiogenesis. CD31 immunohistochemical staining was used for assessing microvessels density and vessels area. Experiments were performed after 24 h, and 3, 7, and 14 days of treatment. RESULTS: DCE-MRI clearly detected the early effect (after 24 h of treatment) of SU6668 on tumor vasculature as a 51% and 26% decrease in the average vessel permeability measured in the tumor rim and core (respectively). A substantial decrease was also observed in average fractional plasma volume in the rim (59%) and core (35%) of the tumor. Histological results confirmed magnetic resonance imaging findings. After 3, 7, and 14 days of treatment, postcontrast magnetic resonant images presented a thin strip of strongly enhanced tissue at the tumor periphery; histology examination showed that this hyperenhanced ring corresponded to strongly vascularized tissue adjacent but external to the tumor. Histology also revealed a strong decrease in the thickness of peripheral viable tissue, with a greatly reduced vessel count. SU6668 greatly inhibited tumor growth, with 60% inhibition at 14 days of treatment. CONCLUSIONS: DCE-MRI detected in vivo the antiangiogenic efficacy of SU6668. 相似文献
40.
Thomas F Hack Tom Pickles Barry D Bultz J Dean Ruether Lorna M Weir Lesley F Degner John R Mackey 《Journal of clinical oncology》2003,21(22):4138-4144
PURPOSE: Women with breast cancer were provided with an audiotape of their primary adjuvant treatment consultation, and the following patient outcomes were measured at 12 weeks postconsultation: perceived degree of information provision, audiotape satisfaction and use, communication satisfaction with oncologist, mood state, and cancer-specific quality of life. PATIENTS AND METHODS: Participants included 628 women newly diagnosed with breast cancer and 40 oncologists from six cancer centers in Canada. The patients were block randomized to one of four consultation groups: standard care control, not audiotaped; audiotaped, no audiotape given; audiotaped, patient given audiotape; and audiotaped, patient offered choice of receiving audiotape or not. RESULTS: Patients receiving the consultation audiotape had significantly better recall of having discussed side effects of treatment than patients who did not receive the audiotape. Audiotape benefit was not significantly related to patient satisfaction with communication, mood state, or quality of life at 12 weeks postconsultation, and was not significantly affected by choice of receiving the audiotape. Patients rated the audiotape intervention positively, with an average score of 83.9 of 100. CONCLUSION: Audiotape provision benefits patients by facilitating their perception of being informed about treatment side effects, but does not significantly influence patient satisfaction with communication, mood state, or quality of life. 相似文献