Visualizing harm reduction: Methodological and ethical considerations.

The use of visual methods is becoming increasingly common and accepted in health research. This paper explores the opportunities and constraints of using photo-based methods in the context of a community-based participatory research study on how to engage people living with HIV in conversations about a hospital's recently introduced harm reduction policy. Using a blended approach of photovoice and photo-elicited interviews, we provided participants (n = 16) with cameras and asked them to take a series of photos that "show how you feel about or have experienced harm reduction as a Casey House client." We reflect on methodological insights from the study to think through the process of doing photo-based work on a stigmatized topic in a small hospital setting by foregrounding: 1) how the act of taking photos assisted participants in visualizing connections between space, harm reduction, and substance use; 2) expectations of participation and navigating daily health realities; and 3) issues of confidentiality, anonymity and stigma in clinical settings. These reflections provide a case study on the importance of critically examining the process of engaging with photo-based methods. We conclude the paper by re-thinking issues of context and photo-based methods. Rather than viewing context as a neutral backdrop to apply a method, context should be viewed as an active force in shaping what can or cannot be done or produced within the space. Photo-based methods may offer an effective community-engagement strategy but may require modification for use in a clinical setting when working on a stigmatized topic with individuals with complex health care needs. Given the potential of visual methods as a community engagement strategy, research teams are advised to understand the entire process as a data collection opportunity so that these methods can be further explored in a variety of contexts.

Living with addiction: the perspectives of drug using and non-using individuals about sharing space in a hospital setting.

Hospitals seem to be places where harm reduction approaches could have great benefit but few have responded to the needs of people who use drugs. Drawing on recent theoretical contributions to harm reduction from health geography, we examine how the implementation of harm reduction is shaped by space and contested understandings of place and health. We examine how drug use and harm reduction approaches pose challenges and offer opportunities in hospital-based care using interview data from people living with HIV and who were or had recently been admitted to a hospital with an innovative harm reduction policy. Our data reveal the contested spatial arrangements (and the related practices and corporeal relations) that occur due to the discordance between harm reduction and hospital regulatory policy. Rather than de-stigmatising drug use at Casey House Hospital, the adoption of the harm reduction policy sparked inter-client conflict, reproduced dominant discourses about health and drug users, and highlights the challenges of sharing space when drug use is involved. The hospital setting produces particular ways of being for people who use and those who do not use drugs and the demarcation of space in a drug using context. Moving forward, harm reduction practice and research needs to consider more than just interactions between drug users and healthcare providers, or the role of administrative policies; it needs to position ethics at the forefront of understanding the collisions between people, drug use, place, and space. We raise questions about the relationship between subjectivity and spatial arrangements in mediating the success of harm reduction.

Bolus injection of aqueous antigen leads to a high density of T-cell-receptor ligand in the spleen, transient T-cell activation and anergy induction.

In vivo anergy can be modelled by administration of soluble peptide to T-cell receptor (TCR) transgenic mice specific for the moth cytochrome c peptide 88-103 (MCCp). Two weeks after initial peptide treatment, T cells were present in normal numbers but were unresponsive to antigen stimulation in vitro. Only bolus injections of peptide, either subcutaneous or intravenous, were effective at inducing tolerance, while slowly released antigen administered via mini-osmotic pump failed to result in anergy. Examination of T cells soon after bolus peptide administration revealed that anergy induction was preceded by a transient hyperactivation of T cells in vivo. Within 2 hr of peptide treatment, interleukin-2 was detectable in the plasma of the transgenic mice. Interestingly, only bolus injections of peptide led to high levels of T-cell activation, while adjuvant emulsified and pump-administered peptide resulted in very low stimulation in vivo. When the dose of bolus-injected peptide used for tolerization was titrated, the extent of anergy induction directly correlated with the intensity of early T-cell activation. Indirect measurements of TCR-ligand density on the surface of antigen-presenting cells following peptide administration revealed that aqueous peptide delivered via bolus injection generated a large number of major histocompatibility complex-peptide complexes, while pump-delivered and adjuvant-emulsified peptide did not. These data suggest that high levels of TCR ligand are required for in vivo T-cell hyperactivation and induction of anergy.

Immediate hemodynamic effects of thrombolytic therapy on the ischemic myocardium.

Thrombolytic agents are used to restore coronary artery perfusion and limit the size of a myocardial infarction. The systemic effects of these drugs, streptokinase (SK), urokinase (UK), and recombinant tissue plasminogen activator (rtPA), have been studied extensively. Although their effects on rheology and late myocardial performance have been well-documented to date, there have not been any studies evaluating the acute hemodynamic consequences of thrombolytics immediately after administration. In this report we use an isolated Langendorf rodent heart preparation to evaluate the acute hemodynamic effects of thrombolytic therapy on both the normal and the ischemic myocardium. We quantified performance by documenting cardiac output, coronary blood flow, and blood pressure. Although each thrombolytic agent significantly transiently impairs cardiac performance, differences in effect between the agents were statistically insignificant. This was also the case with both the normal as well as the ischemic myocardium. The results of this study would not support favoring the use of one of these agents over the other with regards to primary myocardial performance.

Modulation of alloreactivity in transplant recipients by phenotypic manipulation of donor endothelium.

Phenotypic manipulation of allograft endothelium to reduce immunogenicity would have a significant impact on transplantation. In this study we have demonstrated that random seeding of a heart allograft with endothelium, of host origin, not only promotes long-term survival, but reduces the requirement for pharmacologic immunosuppression. We propose that this simple technology could easily be extrapolated to the clinical arena where hypothermia and preservation solutions have allowed allografts to remain ex vivo for extended periods.

The haemostatic effectiveness of autologous platelet rich plasma sequestered after heparin administration and institution of cardiopulmonary bypass.

Preoperative harvesting and postoperative reinfusion of autologous platelet rich plasma (PRP) has been reported to decrease blood loss as well as the requirement for homologous blood transfusion following cardiopulmonary bypass (CPB). We have developed a technique of intraoperative PRP sequestration which occurs during the initial period of CPB after the patient's circulation is supported and heparin has been given (PRP+). This process does not require any additional hardware, personnel or expense and it is performed without difficulty or complication. To evaluate the effect of PRP+ sequestration and reinfusion on blood loss and homologous blood requirement after CPB, we randomly assigned 126 consecutive patients undergoing elective open heart surgery into the experimental group 1 (PRP+) (n = 64) or the control (no platelet pheresis) group 2 (n = 52). A third group (n = 10) were not included in the randomization. Patients in group 3 had PRP prepared by conventional techniques (PRPc) prior to heparin administration and given to the patient after protamine infusion. Aggregation and activation studies were performed on the PRP+, PRPc, and blood bank platelets (BBP). Per cent aggregation of PRP in response to ADP was superior to that of BBP. There were no significant differences in ADP induced aggregation between PRP+ and PEPc. There was no significant difference in platelet activation (CD62) or number between the three groups. Patients infused with PRP+ showed significantly increased aggregation to ADP when compared with untreated patients 120 minutes after return to the ICW. Furthermore, more homologous haemostatic components (platelets/fresh frozen plasma) were required in the control group. We have demonstrated that collection of autologous PRP+ after administration of heparin does not interfere with its haemostatic effectiveness compared with PRPc prepared before the initiation of bypass. Moreover, this can be performed universally in haemodynamically unstable patients without any additional costs.

Effects of in utero administration of alcohol on alcohol sensitivity in adult rats.

In utero exposure to alcohol has been associated with many physical deficits and behavioral abnormalities. The purpose of these studies was to determine the effects of in utero administration of alcohol on behaviors related to tolerance and sensitivity to alcohol in adult rats. Pregnant rats were maintained on a liquid diet containing alcohol [35% ethanol-derived calories (EDC)] throughout pregnancy. Offspring manifested physical characteristics of Fetal Alcohol Syndrome. The 35% EDC group was able to stay on a wooden dowel longer and at higher blood alcohol concentrations than were pair-fed controls. Following a hypnotic dose of alcohol, rats in the 35% EDC group slept longer than pair-fed controls. A greater alcohol-induced hypothermic effect was seen in females in the 35% EDC group than in controls. Treatment did not affect rate of metabolism of alcohol. These studies suggest that in utero administration of alcohol may be a factor in determining an individual's sensitivity and tolerance to alcohol and possibly their preference for alcohol.

CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung.

Bombesin-like peptides are essential autocrine growth factors for many small cell carcinomas (SCCas) of the lung. Herein, we demonstrate that these malignant pulmonary neuroendocrine cells express low levels of the cell surface metalloendopeptidase CD10/neutral endopeptidase 24.11 (CD10/NEP, common acute lymphoblastic leukemia antigen) and that this enzyme hydrolyzes bombesin-like peptides. The growth of bombesin-like peptide-dependent SCC as is inhibited by CD10/NEP and potentiated by CD10/NEP inhibition. The results provide evidence that CD10/NEP is involved in the regulation of tumor cell proliferation. Since SCCa of the lung occurs almost exclusively in cigarette smokers and cigarette smoke inactivates CD10/NEP, decreased cell surface CD10/NEP enzymatic activity may be causally related to the development of SCCa of the lung.

CD10 (CALLA)/neutral endopeptidase 24.11 modulates inflammatory peptide-induced changes in neutrophil morphology, migration, and adhesion proteins and is itself regulated by neutrophil activation.

The common acute lymphoblastic leukemia antigen (CALLA, CD10), which is expressed on early lymphoid progenitors and neutrophils, is the zinc metalloprotease, neutral endopeptidase 24.11 (NEP, "enkephalinase"). The CD10 cell surface enzyme is known to hydrolyze a variety of biologically active peptides including met-enkephalin, formyl-met-leu-phe (f-MLP), and substance P. These three CD10/NEP substrates induce the migration and aggregation of neutrophils, suggesting that each of the peptides can function as a mediator of neutrophil inflammatory responses. Recently, inhibition of CD10/NEP was found to reduce the concentration of metenkephalin needed to activate human and invertebrate granulocytes by several orders of magnitude. Herein we show that f-MLP and substance P induce rapid changes in neutrophil morphology, migration, and adhesion molecule expression, including upregulation of Mo1 (CD11b/CD18) and shedding of LAM-1 (also known as LECAM-1, Leu8, or TQ-1, the human homologue of murine gp100MEL14). Importantly, these coordinated changes are potentiated by inhibition of cell surface CD10/NEP enzymatic activity. Neutrophil cell surface CD10/NEP enzymatic activity is also shown to be regulated by the activation state of the cell during the time period in which the enzyme has its most pronounced effects. These results suggest that in neutrophils, CD10/NEP functions to control responsiveness to multiple inflammatory peptides.

Downregulation of enkephalin-mediated inflammatory responses by CD10/neutral endopeptidase 24.11.

The antigen CD10 (common acute lymphoblastic leukaemia antigen), which is the zinc metalloprotease, neutral endopeptidase 24.11 (also known as NEP or 'enkephalinase'), is expressed by acute lymphoblastic leukaemias, normal lymphoid progenitors, mature polymorphonuclear leukocytes and certain nonhaematopoietic cells. CD10/NEP hydrolyses several naturally occurring peptides, including the endogenous opioid pentapeptides Met- and Leu-enkephalin. In invertebrate organisms such as the mollusc Mytilus edulis, Met-enkephalin triggers inflammatory responses by inducing morphological changes, directed migration and aggregation of haemocytes. We report here that a structure related to CD10/NEP is expressed by M. edulis haemocytes and that abrogation of CD10/NEP enzymatic activity reduces the amount of Met-enkephalin required for haemocyte activation by five orders of magnitude. Similar results are obtained with CD10+ human polymorphonuclear leukocytes, indicating that CD10/NEP related structures regulate enkephalin-mediated inflammatory responses in organisms whose ancestors diverged approximately 500 million years ago.

Influence of daily sodium intake on vasopressin secretion and drinking in dogs.

Studies were carried out to determine the relationship between daily sodium intake, drinking, and vasopressin (AVP) secretion in normal conscious dogs. Chronic responses to 5-day elevations of daily sodium intake (200 meq/day) and 2-wk decreases in daily sodium intake (5 meq/day) were determined. Dogs were studied with ad libitum drinking and with water intake restricted to the amount drunk during the normal-sodium (30 meq/day) control period. Although acute elevations of plasma AVP occurred after a normal (40 meq Na) gastric load, chronic high-sodium intake resulted in no change of steady-state plasma AVP levels or daily AVP excretion (UAVP) with ad libitum drinking. Total water intake and frequency of drinking, however, increased nearly fourfold. In the absence of excess drinking, plasma AVP and UAVP both exhibited a nearly sixfold increase during the period of high-sodium intake. Despite elevations of plasma AVP, daily urine volume increased and urine osmolality rose only gradually during the 5 days of high-sodium intake. Chronic low-sodium intake also did not alter plasma AVP, but total water intake was reduced 20%. The data indicate that with water available, extracellular osmolality is controlled predominantly by drinking rather than by AVP secretion, that either osmolality or sodium concentration is the predominant controller of drinking and AVP secretion, and that daily water excretion need not be related directly to plasma AVP.

Vasopressin, fluid, and electrolyte response to chronic angiotensin II infusion.

The chronic interrelationships between blood-borne angiotensin (AII), plasma arginine vasopressin (AVP), fluid and electrolyte balance, and mean arterial pressure (AP) were studied in mongrel dogs by continuous intravenous infusion of AII for 7 days. Two groups of dogs were infused: group 1 and group 2 received 5.0 and 20.0 ng AII . kg-1 . min-1, respectively, and each were studied first on ad lib H2O intake and then several weeks later with "fixed" water intake. Plasma AVP was determined utilizing a sensitive radioimmunoassay procedure described herein, Group 1 (5.0 ng AII): AP rose to a steady-state level nearly 20 mmHg above control by the 3rd day of AII infusion with both ad lib and "fixed" H2O intake. With ad lib H2O, AVP was chronically unchanged while with fixed H2O a significant decrease had occurred by the 2nd day of AII infusion. Plasma [Na] and osmolality were not significantly changed in either state. Group 2 (20.0 ng AII): AP rose nearly 40 mmHg above control by the 3rd day of infusion with both ad lib and fixed water intake. AVP did not change significantly from a control of 0.8 microU/ml throughout AII infusion with ad lib H2O intake but drinking was more than doubled. With fixed H2O intake, plasma AVP rose from a control of 0.8 microU/ml to an average of 1.3 microU/ml over the last 4 days of AII infusion. A negative correlation was obtained between the "cumulative H2O balance" and plasma AVP obtained during AII infusion. We conclude first that circulating AII is not directly involved in the long-term control of AVP secretion and, second, neither AVP nor enhanced drinking contributes significantly to AII-induced hypertension.

Influence of sodium and parathyroid hormone on calcium release from intestinal mucosal cells.

The uptake and release of (45)Ca from the intestinal mucosal epithelium were investigated under a variety of conditions. The initial rate of uptake characterized a calcium pool with a half-time of saturation of less than 2 min. The entry of (45)Ca into this pool was inhibited by NaCN and ethacrynic acid and was stimulated by the removal of Cl(-) from the incubation. The initial rate of (45)Ca release was also inhibited by NaCN and removal of Na(+) from the incubation. Parathyroid hormone administration enhanced the release of (45)Ca from cells prepared from parathyroid-ectomized animals. These observations suggest that calcium transport across the brush border and basallateral membranes are identifiable components of the kinetics of (45)Ca uptake and release and that parathyroid hormone stimulates a sodium-dependent mechanism of calcium transport across the basal-lateral membranes.

Plasma lipoproteins in liver disease. I. Immunologically distinct low-density lipoproteins in patients with biliary obstruction.

Sera from patients with extrahepatic biliary obstruction were found to have an abnormal lipoprotein (obstructive lipoprotein) which failed to react with antibodies to normal lipoproteins of d < 1.063. Preparations of this abnormal lipoprotein made by a combination of immunoprecipitation and multiple polyanion precipitations revealed a high content of free cholesterol (26%) and phospholipids (61%) but only trace amounts of cholesterol esters and triglycerides. Protein content varied from 13% to a corrected low of 5% when ultracentrifugation was also performed. Amino acid analyses of the latter preparations resembled that of lipoproteins of d < 1.006. The reasons underlying the apparent unreactivity of the abnormal lipoprotein were explored. No evidence could be found for soluble antigen-antibody complexes of gamma-globulin and the abnormal lipoprotein, nor for inhibition of antigen-antibody complex formation by serum factors. Purified preparations of obstructive lipoprotein did not react with antisera to high- or low-density lipoproteins prepared from normal sera. Moreover, rabbits immunized with the abnormal lipoproteins produced specific antibodies to this lipoprotein which reacted with a d < 1.006 lipoprotein in normal sera. All other lipoprotein fractions from normal sera were unreactive. It is not known whether this lipoprotein is abnormal by virtue of the presence of a unique peptide or because of secondary alterations in lipoprotein structure.