In vivo visualization of hemodialysis-induced alterations in leukocyte-endothelial interactions

BACKGROUND: The aim of this study was to develop a model for hemodialysis (HD) in small animals using conventional dialysis equipment that would allow the intravital microscopic observation of leukocyte-endothelial interactions in vivo. METHODS: Cuprophan dialyzers were adapted to obtain a similar ratio of membrane area to blood volume as in clinical HD. A silicone ring was inserted into the dialyzer's inlet to limit the number of blood-perfused capillaries. Rabbits were dialyzed for one hour without a dialysate flow. RESULTS: Extracorporeal circulation with the cuprophan dialyzer resulted in a transient leukopenia and complement activation. At the nadir of leukopenia, leukocytes that rolled along the venular wall were scarcely observed, whereas rolling was abundant (54 +/- 9 per min) prior to extracorporeal circulation. The adhesion of leukocytes to the vascular endothelium was not induced. After 60 minutes, rolling of leukocytes was still reduced by 73 +/- 5.5%, despite the full recovery of circulating leukocyte counts. Extracorporeal circulation without a dialyzer also tended to reduce leukocyte rolling, although systemic leukocyte counts were not affected. CONCLUSIONS: The use of adapted conventional cuprophan hemodialyzers in rabbits yielded a transient leukopenia similar to that in clinical HD. Using intravital microscopy, we demonstrated impairment of leukocyte-endothelial interactions. In addition, our data indicate that tissues, in which leukocytes can roll and adhere, are not automatically sites of leukocyte sequestration during HD-induced leukopenia.     

Referral patterns of physicians requesting brain MRI procedures: a community-based study

The results of the brain MRI procedures (n = 490) performed in a medium-sized community with a single MRI unit were reviewed. The non-neurologic medical practitioners ordered nearly as many brain scans as the neurospecialists (40.8% and 59.2% of the total scans respectively). The incidence of abnormal scans was 29.5% for the group of non-neurospecialists and 39.3% for the neurospecialists. A fairly large proportion (26.7%; n = 131) of the scans were requested to evaluate headaches. Twelve patients (9.2%) with headaches but without clear neurologic localizing features showed intracranial abnormalities in their MRI scans. Some of the abnormalities observed in the brain MRI scans could have been detected by a CT procedure.     

Biochemical Modulation of Aracytidine (Ara-C) Effects by GTI-2040, a Ribonucleotide Reductase Inhibitor, in K562 Human Leukemia Cells

GTI-2040 is a potent antisense to the M2 subunit of the ribonucleotide reductase (RNR), an enzyme involved in the de novo synthesis of nucleoside triphosphates. We hypothesized that combination of GTI-2040 with the cytarabine (Ara-C) could result in an enhanced cytotoxic effect with perturbed intracellular deoxynucleotide/nucleotide (dNTP/NTP) pools including Ara-C triphosphate (Ara-CTP). This study aims to provide a direct experimental support of this hypothesis by monitoring the biochemical modulation effects, intracellular levels of Ara-CTP, dNTPs/NTPs following the combination treatment of Ara-C, and GTI-2040 in K562 human leukemia cells. GTI-2040 was introduced into cells via electroporation. A hybridization-ligation ELISA was used to quantify intracellular GTI-2040 concentrations. Real-time PCR and Western blot methods were used to measure the RNR M2 mRNA and protein levels, respectively. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay was used to measure the cytotoxicity following various drug treatments. A non-radioactive HPLC-UV method was used for measuring the intracellular Ara-CTP, while a LC-MS/MS method was used to quantify intracellular dNTP/NTP pools. GTI-2040 was found to downregulate M2 mRNA and protein levels in a dose-dependent manner and showed significant decrease in dNTP but not NTP pool. When combining GTI-2040 with Ara-C, a synergistic cytotoxicity was observed with no further change in dNTP/NTP pools. Importantly, pretreatment of K562 cells with GTI-2040 was found to increase Ara-CTP level for the first time, and this effect may be due to inhibition of RNR by GTI-2040. This finding provides a laboratory justification for the current phase I/II evaluation of GTI-2040 in combination with Ara-C in patients with acute myeloid leukemia.     

The placenta contributes to activation of the renin angiotensin system in twin-twin transfusion syndrome

The renin-angiotensin system (RAS) in twin-twin transfusion syndrome (TTTS) is up-regulated in the donor fetus's kidneys, but down-regulated in the recipient's. Ultrasonographic and echocardiographic features suggest that the recipient is also exposed to RAS components. In this study we investigated the role and origin of RAS components in the recipient fetus. Monochorionic diamniotic (MCDA) pregnancies were recruited from a tertiary fetal medicine service. Cord blood was collected from MCDA twins (TTTS and control non-TTTS) at delivery for renin and angiotensin II immunoassays. Placental tissue was flash-frozen for mRNA and protein expression or formalin-fixed for immunohistochemistry. Archival placenta and kidney samples were used for immunohistochemistry and in-situ hybridization. Plasma renin levels were elevated (p<0.05) in recipients (median 201pg/ml, range 54-315pg/ml) and donors (125pg/ml, 25-296) with TTTS compared to controls (2.5pg/ml, 1.1-1.5pg/ml). The same was found with angiotensin II with high levels in both recipients (300.5pg/ml, 86.1-488pg/ml) and donors (239pg/ml, 76.6-422) compared to controls (169.5pg/ml, 89-220pg/ml, p<0.05). Renin mRNA expression, and protein appeared qualitatively higher in the placental territory of the recipient compared to that of the donor and non-TTTS controls. We conclude that both fetuses in TTTS are exposed to high levels of RAS components; these appear to be produced from different sites, namely the kidney of the donor, and the placenta of the recipient. Given the markedly different phenotypes in the genetically identical fetuses with TTTS, we suggest that the source of RAS components may influence their clinical manifestations.     

Dissatisfaction with body size among low-income, postpartum black women

OBJECTIVE: To explore the body size perceptions of low-income, postpartum Black women. DESIGN: Prospective, exploratory survey using a culturally sensitive figure rating scale, to assess body size perceptions. SETTING: Four inner city clinics in Washington, DC. Participants: Low-income, postpartum Black women (N= 105). METHOD: A validated, culturally sensitive figure rating scale was used to assess perception of current, typical, healthy, and preferred body sizes of participants. Derived scores were used to assess other body image measures. MAIN OUTCOME MEASURES: Measures were mean scores of perceived sizes and derived scores representing body size satisfaction, adherence to typical size, and health ideal size. RESULTS: Over 75% of subjects exhibited dissatisfaction with current body size. The perceived size for the typical (reference) woman was larger and not representative of the perceived healthy or preferred sizes of the sample. No difference between preferred and healthy sizes was observed. CONCLUSIONS: Two thirds of the participants were dissatisfied with their current body size and over half desired weight loss. The lack of difference between preferred and healthy body sizes suggests desire for a body size that meets both cultural standards of attractiveness and personal standards of health. Nursing opportunity for engaging in anticipatory interventions is highlighted.     

Antioxidant capacity and phenolic content of selected commercially available cruciferous vegetables

Antioxidant activity, free radical scavenging activity and phenolic content of red cabbage (Brassica oleracea var. capitata rubra), Chinese cabbage (Brassica rapa pekinensis var cylindrica), green cabbage (Brassica oleracea var capitata), mustard cabbage (Brassica juncea var rugosa) and Chinese white cabbage (Brassica rapa var chinensis), grown in Malaysia, were evaluated. Red cabbage had the highest antioxidant activity and phenolic content compared to the other cruciferous vegetables studied (p < 0.05). The contributions of all cruciferous vegetables to the antioxidant activity was >79%. The radical scavenging activity was in the order of Chinese white cabbage > red cabbage > mustard cabbage > Chinese cabbage > green cabbage. There was a significant difference (p < 0.05) in the means of scavenging activity observed between cabbage, Chinese cabbage and Chinese mustard. Phenolic content was significantly different (p < 0.05) among all the cruciferous vegetables studied, and was in the order of red cabbage > Chinese white cabbage > green cabbage > Chinese cabbage >mustard cabbage. The study indicated that red cabbage possessed the highest antioxidant capacity and phenolic compounds concentration among all the cruciferous vegetables studied.     

Minding the gap: health and social care provider perceptions of parental communication and Black-Canadian youths’ sexual health

Abstract

Health and social care providers’ perceptions of Black-Canadian parent-youth sexual health communication has important implications for addressing knowledge gaps in the provision of services to young people and their parents. Providers’ perceptions are crucial as they often act as advisers in tailoring programmes or services to the perceived needs of parents and youth. To understand these perceptions, 17 semi-structured in-depth interviews were conducted with providers who worked with African, Caribbean or Black (ACB) parents and youth in Toronto, Ontario, Canada. Critical Race Theory was used to help guide the interpretation of findings. The findings revealed providers believed that many parents were unlikely to explicitly discuss sexual health or HIV prevention with young people. Additionally, providers perceived that the content of and approach to parent-youth sexual health communication differed between African and Caribbean clients. Moreover, providers believed that both parents’ and young people’s sex and gender impacted the quality, content and style of sexual health communication and had important implications for programme development. Overall, findings suggest a need for understanding the development of providers’ perceptions of this communication, ways to address these perceptions and further parent-provider collaboration to promote Black youths’ sexual health.     

The use of formal and informal knowledge sources in patients’ treatment decisions in secondary stroke prevention: qualitative study

Background There is robust empirical evidence to support clinical decision making in secondary stroke prevention after transient ischaemic attack (TIA) or recovered stroke. However, little attention has been paid to patients’ utilization of this evidence in coming to decisions about their treatment choices. Objective To examine the use of formal and informal knowledge by patients in making decisions about carotid endarterectomy (CEA) and medical treatment after TIA/recovered stroke. Setting and participants Twenty participants were recruited from an outpatient vascular surgical assessment clinic in England. Ten were receiving medical treatment alone, and 10 were undergoing CEA after TIA or recovered stroke. Method Twenty‐eight in‐depth qualitative interviews were conducted. An iterative approach was used whereby emergent themes were further explored in later interviews. Interviews were audiotaped, transcribed and coded. Results Participants gathered and utilized several types of knowledge in the process of making treatment decisions: Empirical knowledge (e.g. clinical trial findings); Pathophysiologic findings (e.g. results of clinical investigations); Experiential knowledge (e.g. personal experience of stroke); Goals and values (e.g. potential impact on family); System features (e.g. apparent urgency of treatment). Conclusions In addition to formal evidence, patients use other sources of informal or ‘non‐evidentiary’ knowledge to support their decisions about treatment after TIA or recovered stroke. To enable evidence‐based patient choice, health professionals need to appreciate the diverse types of evidence which patients use, to help them to access relevant and high‐quality evidence, to balance evidence from different sources and to make choices which are congruent with their values and expectations.