[Population health intervention research, health technology assessment, health services research and intervention implementation research: Convergences and singularities]. / Recherche interventionnelle en santé des populations, évaluation des technologies de santé, recherche sur les services de santé et recherche sur la mise en œuvre des interventions : convergences et particularités.

In public health, intervention is an object of research and evaluation which, over time, has given rise to numerous approaches. The first part of the article proposes to reposition intervention research in population health and intervention evaluation on a continuum. Although the former has a more cognitive objective and the latter a more pragmatic objective, they are not mutually exclusive. The distinction between these two practices is based on the predominance of the following characteristics: the objectives pursued, the scope of the investigations, the regulatory constraints, the financing obtained, the ethical approaches taken, and the deliverables established. The second part of the article offers a glance different fields and approaches within the continuum between these two poles: Health Technology Assessment, Health Services Research and Implementation Research. While all of them have the study of health interventions at their core, but each has developed through specialisation in one or the other type of intervention, in a particular scope or context, in certain evaluation questions, or in specific approaches. all as gateways to the study of public health intervention, these different approaches are by no means mutually exclusive.

Stepped-wedge randomized controlled trial of laparoscopic ventral mesh rectopexy in adults with chronic constipation.

BACKGROUND: The effectiveness of laparoscopic ventral mesh rectopexy (LVMR) in patients with defecatory disorders secondary to internal rectal prolapse is poorly evidenced. A UK-based multicenter randomized controlled trial was designed to determine the clinical efficacy of LVMR compared to controls at medium-term follow-up. METHODS: The randomized controlled trial was conducted from March 1, 2015 TO January 31, 2019. A stepped-wedge RCT design permitted observer-masked data comparisons between patients awaiting LVMR (controls) with those who had undergone surgery. Adult participants with radiologically confirmed IRP refractory to conservative treatment were randomized to three arms with different delays before surgery. Efficacy outcome data were collected at equally stepped time points (12, 24, 36, 48, 60, and 72 weeks). Clinical efficacy of LVMR compared to controls was defined as ≥ 1.0-point reduction in Patient Assessment of Constipation-Quality of Life and/or Symptoms (PAC-QOL and/or PAC-SYM) scores at 24 weeks. Secondary outcome measures included 14-day diary data, the Generalized Anxiety Disorder scale (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), St Marks incontinence score, the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), the chronic constipation Behavioral Response to Illness Questionnaire (CC-BRQ), and the Brief Illness Perception Questionnaire (BIPQ). RESULTS: Of a calculated sample size of 114, only 28 patients (100% female) were randomized from 6 institutions (due mainly to national pause on mesh-related surgery). Nine were assigned to the T0 arm, 10 to T12, and 9 to T24. There were no substantial differences in baseline characteristics between the three arms. Compared to baseline, significant reduction (improvement) in PAC-QOL and PAC-SYM scores were observed at 24 weeks post-surgery (- 1.09 [95% CI - 1.76, - 0.41], p = 0.0019, and - 0.92 [- 1.52, - 0.32], p = 0.0029, respectively) in the 19 patients available for analysis (9 were excluded for dropout [n = 2] or missing primary outcome [n = 7]). There was a clinically significant long-term reduction in PAC-QOL scores (- 1.38 [- 2.94, 0.19], p = 0.0840 at 72 weeks). Statistically significant improvements in PAC-SYM scores persisted to 72 weeks (- 1.51 [- 2.87, - 0.16], p = 0.0289). Compared to baseline, no differences were found in secondary outcomes, except for significant improvements at 24 and 48 weeks on CC-BRQ avoidance behavior (- 14.3 [95% CI - 23.3, - 5.4], and - 0.92 [- 1.52, - 0.32], respectively), CC-BRQ safety behavior (- 13.7 [95% CI - 20.5, - 7.0], and - 13.0 [- 19.8, - 6.1], respectively), and BIPQ negative perceptions (- 16.3 [95% CI - 23.5, - 9.0], and - 10.5 [- 17.9, - 3.2], respectively). CONCLUSIONS: With the caveat of under-powering due to poor recruitment, the study presents the first randomized trial evidence of short-term benefit of LVMR for internal rectal prolapse. TRIAL REGISTRATION: ISRCTN Registry (ISRCTN11747152).

[Describing and disseminating organizational innovation in public health DINOSP ; guide (Description of Organizational Innovations in Public Health)]. / Décrire l'innovation organisationnelle en santé publique pour favoriser sa dissémination ; guide DINOSP (Description des innovations organisationnelles en santé publique).

OBJECTIVES: The transition from experimentation to the scaling up of organizational innovations in public health is arduous. The innovation process requires back-up in view of enhancing the chances of success and generalization. The aim of this article is to present the development of a guide to support the description and analysis of organizational innovations in public health. METHOD: The mobilization of two analysis and description tools, ASTAIRE and TIDIeR, made it possible to select the innovation criteria to be considered for generalization. Collective discussions between actors, decision-makers and researchers and individual interviews with the latter refined and completed the proposed guide, which was reread by experts and tested by project leaders, thereby improving its accuracy and usability. RESULTS: The guide puts forward a two-step approach: i) to describe innovation at two levels: on the one hand, intervention methods, and on the other hand, interventional, population or contextual components corresponding to 27 criteria and ii) to assess the transferability of the innovation by distinguishing its key functions, its formal elements and the margins of maneuver to be maintained. DISCUSSION: The guide presents a modular vision of innovations and leaves room for reflection on its mechanisms. It favors the synchronization of innovations with the existing system and their mutualization. CONCLUSIONS: By putting forward a standardised description of organizational innovations in health and analyzing their effectiveness, the tool can effectively contribute to the development of effective, adaptable and generalizable projects, and thereby contribute to progress in public health.

[Innovative transformation of the health system through a preventive transition]. / L'innovation au service de la transformation du système de santé et du « virage préventif ¼.

Given today's evolution of the healthcare system, organizational transformations, technological developments and major challenges, innovation has taken on primordial importance. In this context and with considerable support, many experimentations have taken place. Unfortunately, few have managed to scale up. What results is a congeries of innovations without a future, possibly avoidable squandering of resources, a number of missed opportunities, and the grim prospect of inventor burnout. As regards prevention, innovation is at the heart of an anticipated "preventive transition" of the health system that has yet to achieve operational status. In this article we attempt to redesign the contours of innovation in health, considering it first and foremost in regard to its social utility. We will go on to explore the limitations of innovative practices that delay the arrival of advances in health. Four types of obstacles appear: faulty evaluation; insufficient dialogue between researchers, stakeholders and decision-makers; lack of visibility and, finally, conceptions and perceptions of innovation characterized by tunnel vision. In the concluding section of this paper, we will present several tracks through which the innovation process could be impelled to drive health system transformation. They consist in: (i) incorporating an evaluative and comprehensive research into innovation processes, (ii) elaborating "bottom-up" approaches giving special consideration to innovations instigated by stakeholders and brought to fruition under real-life conditions, (iii) breaking from standardization by thinking from the outset of the adaptability of innovations and, finally, (iv) tying in the experimental approach with a decision-making process.

Surgery for constipation: systematic review and practice recommendations: Graded practice and future research recommendations.

AIM: This manuscript forms the final of seven that address the surgical management of chronic constipation (CC) in adults. The content coalesces results from the five systematic reviews that precede it and of the European Consensus process to derive graded practice recommendations (GPR). METHODS: Summary of review data, development of GPR and future research recommendations as outlined in detail in the 'introduction and methods' paper. RESULTS: The overall quality of data in the five reviews was poor with 113/156(72.4%) of included studies providing only level IV evidence and only four included level I RCTs. Coalescence of data from the five procedural classes revealed that few firm conclusions could be drawn regarding procedural choice or patient selection: no single procedure dominated in addressing dynamic structural abnormalities of the anorectum and pelvic floor with each having similar overall efficacy. Of one hundred 'prototype' GPRs developed by the clinical guideline group, 85/100 were deemed 'appropriate' based on the independent scoring of a panel of 18 European experts and use of RAND-UCLA consensus methodology. The remaining 15 were all deemed uncertain. Future research recommendations included some potential RCTs but also a strong emphasis on delivery of large multinational high-quality prospective cohort studies. CONCLUSION: While the evidence base for surgery in CC is poor, the widespread European consensus for GPRs is encouraging. Professional bodies have the opportunity to build on this work by supporting the efforts of their membership to help convert the documented recommendations into clinical guidelines.

Surgery for constipation: systematic review and clinical guidance: Paper 1: Introduction & Methods.

AIM: This manuscript provides the introduction and detailed methodology used in subsequent reviews to assess the outcomes of surgical interventions with the primary intent of treating chronic constipation in adults and to develop recommendations for practice. METHOD: PRISMA guidance was adhered to throughout. A literature search was performed in public databases between January 1960 and February 2016. Studies that fulfilled strictly-defined PICOS (patients, interventions, controls, outcome, and study design) criteria were included. The process involved two groups of participants: (i): 'a clinical guidance group' of 18 UK experts (including junior support) who performed the systematic reviews and produced summary evidence statements (SES) based strictly on data synthesis in each review. The same group then produced prototype graded practice recommendations (GPRs) based on coalescence of SES and expert opinion; (ii): a European Consensus group of 18 ESCP (European Society of Coloproctology) nominated experts from nine European countries evaluated the appropriateness of each prototype GPR based on published RAND/UCLA methodology. RESULTS: An overview of the search results is provided in this manuscript. A total of 156 studies from 307 full text articles (from 2551 initially screened records) were included, providing data on procedures characterized by: (i) colonic resection (n = 40); (ii) rectal suspension (n = 18); (iii) rectal wall excision (n = 44); (iv) rectovaginal septum reinforcement (n = 47); (v) sacral nerve stimulation (n = 7). The overall quality of evidence was poor with 113/156 (72.4%) studies providing only Oxford level IV evidence. The best evidence was extracted for rectal excisional procedures, where the majority of studies were Oxford level I or II. The five subsequent reviews provide a total of 99 SES (reflecting perioperative variables, efficacy, harms and prognostic variables) that contributed to 100 prototype GPRs covering patient selection, procedural considerations and patient counselling. The final manuscript details the 85/100 GPRs that were deemed appropriate by European Consensus (remaining 15 were all uncertain) and future research recommendations. CONCLUSION: This manuscript and the following 6 papers suggest that the evidence base for surgical management of chronic constipation is currently poor although some expert consensus exists on best practice. Further studies are required to inform future commissioning of treatments and of research funding.

Eradication of Staphylococcus aureus Catheter-Related Biofilm Infections Using ML:8 and Citrox.

Staphylococci are a leading cause of catheter-related infections (CRIs) due to biofilm formation. CRIs are typically managed by either device removal or systemic antibiotics, often in combination with catheter lock solutions (CLSs). CLSs provide high concentrations of the antimicrobial agent at the site of infection. However, the most effective CLSs against staphylococcal biofilm-associated infections have yet to be determined. The purpose of this study was to evaluate the efficacy and suitability of two newly described antimicrobial agents, ML:8 and Citrox, as CLSs against Staphylococcus aureus biofilms. ML:8 (1% [vol/vol]) and Citrox (1% [vol/vol]), containing caprylic acid and flavonoids, respectively, were used to treat S. aureus biofilms grown in vitro using newly described static and flow biofilm assays. Both agents reduced biofilm viability >97% after 24 h of treatment. Using a rat model of CRI, ML:8 was shown to inactivate early-stage S. aureus biofilms in vivo, while Citrox inactivated established, mature in vivo biofilms. Cytotoxicity and hemolytic activity of ML:8 and Citrox were equivalent to those of other commercially available CLSs. Neither ML:8 nor Citrox induced a cytokine response in human whole blood, and exposure of S. aureus to either agent for 90 days was not associated with any increase in resistance. Taken together, these data reveal the therapeutic potential of these agents for the treatment of S. aureus catheter-related biofilm infections.

In Vitro Approach for Identification of the Most Effective Agents for Antimicrobial Lock Therapy in the Treatment of Intravascular Catheter-Related Infections Caused by Staphylococcus aureus.

Infection of intravascular catheters by Staphylococcus aureus is a significant risk factor within the health care setting. To treat these infections and attempt salvage of an intravascular catheter, antimicrobial lock solutions (ALSs) are being increasingly used. However, the most effective ALSs against these biofilm-mediated infections have yet to be determined, and clinical practice varies greatly. The purpose of this study was to evaluate and compare the efficacies of antibiotics and antiseptics in current clinical use against biofilms produced by reference and clinical isolates of S. aureus Static and flow biofilm assays were developed using newly described in vivo-relevant conditions to examine the effect of each agent on S. aureus within the biofilm matrix. The antibiotics daptomycin, tigecycline, and rifampin and the antiseptics ethanol and Taurolock inactivated established S. aureus biofilms, while other commonly used antistaphylococcal antibiotics and antiseptic agents were less effective. These findings were confirmed by live/dead staining of S. aureus biofilms formed and treated within a flow cell model. The results from this study demonstrate the most effective clinically used agents and their concentrations which should be used within an ALS to treat S. aureus-mediated intravascular catheter-related infections.

Depletion of high-affinity corticosteroid-binding globulin corresponds to illness severity in sepsis and septic shock; clinical implications.

OBJECTIVE: Corticosteroid-binding globulin (CBG) is cleaved by neutrophil elastase converting the high-affinity (haCBG) conformation of CBG to a low-affinity (laCBG) conformation with a ninefold reduced cortisol-binding affinity. These in vitro data suggest that cortisol release by CBG cleavage results in the targeted delivery of cortisol to areas of inflammation. Our objective was to determine whether CBG cleavage alters circulating levels of haCBG and laCBG in vivo in proportion to sepsis severity. DESIGN: Prospective, observational cohort study in an adult tertiary level Intensive Care Unit in Adelaide, Australia. PATIENTS: Thirty-three patients with sepsis or septic shock grouped by illness severity [sepsis, septic shock survivors, septic shock nonsurvivors and other shock]. MEASUREMENTS: Plasma levels of haCBG and laCBG were assessed using a recently developed in-house assay in patients. Plasma total and free cortisol levels were also measured. RESULTS: Plasma total CBG and haCBG levels fell significantly, in proportion to disease severity (P < 0·0001 for both). There was a nonsignificant increase in free and total cortisol as illness severity worsened (P = 0·19 and P = 0·39, respectively). Illness severity was better correlated with haCBG levels than either free or total cortisol levels. CONCLUSIONS: Increasing illness severity in sepsis and septic shock is associated with markedly reduced circulating haCBG concentrations in vivo. We propose that low levels of haCBG in chronic inflammation may limit the availability of cortisol to inflammatory sites, perpetuating the inflammatory process.

Degradation parameters of amaranth, barley and quinoa in alpacas fed grass hay.

This study was conducted to determine the compartment 1 (C1) characteristics of alpacas (fistulated male, 7 ± 1.5 years old, 61 ± 5 kg BW) fed grass hay (GH) supplemented with amaranth (AM), quinoa (Q) and barley (B) grains. Alpacas were provided water ad libitum while housed in metabolism crates. The GH and GH plus treatments were fed at 0700 every day. Treatment periods were for 14 days in which GH or GH plus one of the grain treatments were randomly allocated. On day 14, volatile fatty acids (VFA), pH and ammonia nitrogen (NH3 -N) were determined at 1, 3, 6, 10, 14, 18 and 24 h post-feeding. C1 degradation of each feed component was also determined with the alpacas being fed GH only and the samples incubated for 0, 2, 4, 8, 14, 24, 48 and 72 h. Dry matter (DM), neutral detergent fibre (NDF) and crude protein (CP) were determined and were divided into three categories: a = immediately soluble; b = the non-soluble but degradable; and u = non-degradable/unavailable, potential extent of degradation (PE), degradation rate (c) and effective degradation (ED). C1 passage rate was determined using acid detergent insoluble ash as a marker and was calculated to be 5.5%∙h-1. Total DM intake was highest (p < 0.05) for B and resulted in a higher (p < 0.05) CP intake. GH and AM were different in mean pH (6.81 and 6.66, respectively). B NH3 -N was greater (p < 0.05) than the other treatments. Total VFA was greatest (p < 0.05) for AM, with the greatest composition differences being a shift form acetate percentage to butyrate. DM, NDF and CP degradation was different across the treatments, where PE and ED were higher (p < 0.05) for the grain treatments. The pseudo-grains AM and Q had similar C1 degradation characteristics to B.

Disentangling the effect of growth from development in size-related trait scaling relationships.

In plant ecology, the terms growth and development are often used interchangeably. Yet these constitute two distinct processes. Plant architectural traits (e.g. number of successive forks) can estimate development stages. Here, we show the importance of including the effect of development stages to better understand size-related trait scaling relationships (i.e. between height and stem diameter). We focused on one common savanna woody species (Senegalia nigrescens) from the Greater Kruger Area, South Africa. We sampled 406 individuals that experience different exposure to herbivory, from which we collected four traits: plant height, basal stem diameter, number of successive forks (proxy for development stage), and resprouting. We analysed trait relationships (using standardized major axis regression) between height and stem diameter, accounting for the effect of ontogeny, exposure to herbivory, and resprouting. The number of successive forks affects the scaling relationship between height and stem diameter, with the slope and strength of the relationship declining in more developed individuals. Herbivory exposure and resprouting do not affect the overall height-diameter relationship. However, when height and stem diameter were regressed separately against number of successive forks, herbivory exposure and resprouting had an effect. For example, resprouting individuals allocate more biomass to both primary and secondary growth than non-resprouting plants in more disturbed conditions. We stress the need to include traits related to ontogeny so as to disentangle the effect of biomass allocation to primary and secondary growth from that of development in plant functional relationships.

[Aging well in the 20th century: a psychosocial perspective]. / 'Aging well' in de 21e eeuw: een psychosociaal perspectief.

Aging well refers to retaining or restoring well-being in the face of various age-related changes in later life. This process is influenced by the quality of social relationships and active adaptation to loss and change. According to recent studies from the Longitudinal Aging Study Amsterdam, more older adults are maintaining relationships with friends, colleagues and other non-kin longer. Greater diversity in their social networks contributes to happiness and morale, and provides protection against anxiety, depression and loneliness. There is also a slight increase in mastery and in cognitive functioning among new cohorts of older adults. These developments promote adaptation to declines in health and loss of the partner. These improvements are found less frequently among those with lower education, lower incomes, and/or small networks. Several interventions have proven to be effective for these disadvantaged groups: a visiting service for widows and widowers and two self-management interventions for chronically ill or physically vulnerable older adults.

[Caring friends and neighbors as informal caregivers of older adults: A comparison with offspring]. / Zorgzame vrienden en buren als mantelzorgers van oudere volwassenen: een vergelijking met kinderen.

This study compared informal care to older, non-coresiding adults provided by friends and neighbours and informal care by children or their partners. Using data from a Dutch representative survey among informal caregivers conducted by CBS and SCP, caregivers of friends (n=133), neighbours (n=108) and parents (n=1,008) were compared with one another to investigate care that friends and neighbours provide to the elderly non-coresiding adults (age 55 and over). Nine percent of those providing care to someone outside the household were friends and nine percent were neighbours. Friends, like children, usually provide long-lasting care, up to four or five years. Friends are similar to neighbours in the number of hours that they provide care. Friends and neighbours experience a lower caregiver burden than children. However, when fulfilling multiple caring tasks, both friends and children, have a greater chance of experiencing higher levels of burden. When there were other caregivers to help, friends experienced a small reduction in burden. Friends and neighbours deserve to be recognized as informal caregivers by policy makers and they deserve attention and support along with family caregivers.

Approaches to the detection of Clostridioides difficile in the healthcare environment.

Clostridioides difficile, a spore-forming bacillus, is a major cause of healthcare-associated infection, and can survive for prolonged periods in the inanimate environment. Environmental sampling to detect C. difficile is not routine but may be undertaken as part of outbreak management and during research projects. We conducted a literature search covering the period between 1980 and 2018 to review methods for the detection of this pathogen in the environment. There are many acceptable sampling methods used for environmental screening, including contact plates, cotton swabs, flocked swabs and sponges. Most recent studies suggest that sponges are the most effective method of sampling and have the added benefit of being capable of sampling larger and curved areas. Culture methods are the most common laboratory method of detecting C. difficile from environmental samples. However, the results are variable depending on the type of agar used and the turnaround times can be long. Molecular methods such as real-time polymerase chain reaction (RT-PCR), although more commonly used to detect C. difficile from faecal specimens, has been used with varying degrees of success in environmental sampling. Further studies are needed to determine whether molecular techniques could offer a more reliable, faster method of environmental sampling, giving infection prevention and control teams more reassurance that patients are being placed in adequately decontaminated hospital environments.

A feasibility study of trauma-sensitive obstetric care for low-income, ethno-racial minority pregnant abuse survivors.

PURPOSE: This study evaluated the feasibility and acceptability of an integrated (psychological and obstetric) intervention for pregnant abuse survivors with posttraumatic stress symptoms (PTS) from low-income, ethno-racial minority backgrounds. METHODS: Trauma-sensitive obstetrics to promote control, anxiety-reduction and empowerment (TO-CARE) offers cognitive-behavioral therapy (CBT) coping skills delivered over six sessions by therapists, coupled with trauma-sensitive obstetric care from specially-trained obstetric physicians. RESULTS: Participants were 21 women who completed at least three sessions of CBT, totaling 51.2% of eligible participants. Participants received approximately one-third (M = 2.29; SD = 2.15) of their prenatal visits with obstetric residents trained in trauma-sensitive care. Nearly all participants (95%) reported that they benefited from the intervention. Although most participants demonstrated improvement in PTS, only four demonstrated reliable improvement, and two demonstrated reliable improvement in depression symptoms. These improvements appeared to be maintained at postpartum follow-up for two of the participants. CONCLUSIONS: Our findings suggest that TO-CARE was acceptable to pregnant abuse survivors and may be a promising intervention to reduce symptoms of distress. Implications of the low retention rate for the CBT (51.2%) are discussed in the context of interventions for low-income minority pregnant women. Limitations regarding feasibility of the integrated intervention are discussed.

Potential use of targeted enzymatic agents in the treatment of Staphylococcus aureus biofilm-related infections.

Staphylococcus aureus is a leading cause of healthcare-associated infections. The ability of S. aureus to attach and subsequently accumulate on the surfaces of implanted medical devices and in host tissues makes infections caused by this pathogen difficult to treat. Current treatments have been shown to have limited effect on surface-associated S. aureus, and may be enhanced by the addition of a dispersal agent. This study assessed the enzymatic agents dispersin B, lysostaphin, alpha amylase, V8 protease and serrapeptase, alone and in combination with vancomycin and rifampicin, against biofilms formed by meticillin-resistant and -susceptible strains of S. aureus. The efficacy of both antibiotics was enhanced when combined with any of the dispersal agents. Lysostaphin and serrapeptase were the most effective dispersal agents against all strains tested. These data indicate that combinations of biofilm dispersal agents and antibiotics may extend the therapeutic options for the treatment of S. aureus biofilm-associated infections.

Current and future approaches to the prevention and treatment of staphylococcal medical device-related infections.

Staphylococci, in particular Staphylococcus aureus and Staphylococcus epidermidis, are a leading cause of healthcare-associated infections. Patients who have a medical device inserted are at particular risk of an infection with these organisms as staphylococci possess a wide range of immune evasion mechanisms, one of which being their ability to form biofilm. Once embedded in a biofilm, bacteria are inherently more resistant to treatment with antibiotics. Despite advances in our understanding of the pathogenesis of staphylococcal biofilm formation, medical devices colonised with biofilms frequently require removal. New and novel approaches to prevent and treat biofilm infections are urgently required. In recent years, progress has been made on approaches that include antiadhesive strategies to prevent surface adhesion or production of bacterial adhesins, dissolution of already established biofilm, targeting of biofilm matrix for degradation and interference with biofilm regulation. Several obstacles need to be overcome in the further development of these and other novel anti-biofilm agents. Most notably, although in vitro investigation has progressed over recent years, the need for biofilm models to closely mimic the in vivo situation is of paramount importance followed by controlled clinical trials. In this review we highlight the issues associated with staphylococcal colonisation of medical devices and potential new treatment options for the prevention and control of these significant infections.

Effect of chronic administration of selective 5-hydroxytryptamine and noradrenaline uptake inhibitors on a putative index of 5-HT2C/2B receptor function.

Chronic treatment with selective 5-HT reuptake inhibitors (SSRI) are therapeutic in obsessive compulsive disorder, depression, anxiety, bulimia nervosa and migraine. In the present study the possibility that SSRI's act by desensitizing 5-HT2C/5-HT2B receptors was assessed using a putative in vivo model of 5-HT2C/5-HT2B receptor function, mCPP-induced hypolocomotion. mCPP (2, 4 and 6 mg/kg i.p. 20 min pretest) reduced locomotion and rears in rats treated acutely or chronically with saline. Acute oral administration of the SSRI's fluoxetine (10 mg/kg), paroxetine (10 mg/kg), or clomipramine (70 mg/kg) or the noradrenaline reuptake inhibitor, desipramine (10 mg/kg), all 1 hr pretest, did not prevent mCPP-induced hypolocomotion. In contrast, chronic treatment with the SSRI's paroxetine and fluoxetine (both 10 mg/kg p.o. daily x 21 days), significantly attenuated the effect of mCPP (4 and 6 mg/kg i.p.) on locomotion and rears 24 hr after the last pretreatment dose. Chronic clomipramine (70 mg/kg p.o. daily x 21 days) also significantly attenuated the effect of mCPP (4 mg/kg i.p.) on rears and tended to reduce the hypolocomotor response. However, chronic treatment with desipramine, (10 mg/kg p.o. daily x 21) had no effect on any of the parameters measured. As chronic fluoxetine and paroxetine did not reduce brain mCPP levels (determined by HPLC 30 min after 4 mg/kg i.p.) the results suggest that chronic SSRI's, but not desipramine, reduce 5-HT2C/5-HT2B receptor responsivity. If this occurs in man, it may mediate or contribute to their reported therapeutic efficacy in depression, anxiety, bulimia, migraine and alcoholism. It may also be of particular relevance to their unique efficacy in OCD.

Xenografts--future prospects for clinical transplantation.

This paper outlines the basic problems that still need to be overcome before xenografting becomes a reality. It presents evidence that if the first of these problems (preformed or natural antibody to pig) can be overcome then pig kidneys will: (a) not hyperacutely reject from a human; and (b) will not, under currently used immunosuppression, induce massive new primary or secondary responses. It also makes brief justification of the use of the pig as the donor of choice and outlines what essential animal work we feel necessary before an actual pig-to-human transplant is contemplated.

Haemorrhagic endovasculitis of the placenta: a review with clinical correlation.

Haemorrhagic endovasculitis (HEV) is a recently described vasodestructive process within the placenta. Similarities to several forms of thrombotic microangiopathy are evident. Clinical studies have shown strong associations between HEV, still birth and intrauterine growth retardation (IUGR). Liveborn infants, with affected placentae, evaluated at the age of five, exhibit a high incidence of neurological abnormalities. HEV has been recurrent in successive pregnancies in some patients. Clinicopathological processes, which appear to be associated with HEV, include the presence of chronic villitis (VUA) and maternal hypertension. Viral- and/or Mycoplasma-type particles have been identified in a number of affected placentae examined by electron microscopy. Associated pathological events suggest an infectious aetiology possibly acting in concert with an environmental toxin. Biochemical factors and alterations of immune response within the maternal-placental-fetal unit may be involved.