Two physically, functionally, and developmentally distinct peritoneal macrophage subsets

The peritoneal cavity (PerC) is a unique compartment within which a variety of immune cells reside, and from which macrophages (Mempty set) are commonly drawn for functional studies. Here we define two Mempty set subsets that coexist in PerC in adult mice. One, provisionally called the large peritoneal Mempty set (LPM), contains approximately 90% of the PerC Mempty set in unstimulated animals but disappears rapidly from PerC following lipopolysaccharide (LPS) or thioglycolate stimulation. These cells express high levels of the canonical Mempty set surface markers, CD11b and F4/80. The second subset, referred to as small peritoneal Mempty set (SPM), expresses substantially lower levels of CD11b and F4/80 but expresses high levels of MHC-II, which is not expressed on LPM. SPM, which predominates in PerC after LPS or thioglycolate stimulation, does not derive from LPM. Instead, it derives from blood monocytes that rapidly enter the PerC after stimulation and differentiate to mature SPM within 2 to 4 d. Both subsets show clear phagocytic activity and both produce nitric oxide (NO) in response to LPS stimulation in vivo. However, their responses to LPS show key differences: in vitro, LPS stimulates LPM, but not SPM, to produce NO; in vivo, LPS stimulates both subsets to produce NO, albeit with different response patterns. These findings extend current models of Mempty set heterogeneity and shed new light on PerC Mempty set diversity, development, and function. Thus, they introduce a new context for interpreting (and reinterpreting) data from ex vivo studies with PerC Mempty set.

Circulating Interleukin-6 and High-Sensitivity C-Reactive Protein Decrease After Periodontal Therapy in Otherwise Healthy Subjects

Background: Periodontal disease has been associated with many chronic inflammatory systemic diseases, and a common chronic inflammation pathway has been suggested for these conditions. However, few studies have evaluated whether periodontal disease, in the absence of other known inflammatory conditions and smoking, affects circulating markers of chronic inflammation. This study compared chronic inflammation markers in control individuals and patients with periodontal disease and observed whether non-surgical periodontal therapy affected inflammatory disease markers after 3 months. Methods: Plasma and serum of 20 controls and 25 patients with periodontal disease were obtained prior to and 3 months after non-surgical periodontal therapy. All patients were non-smokers, they did not use any medication, and they had no history or detectable signs and symptoms of systemic diseases. Periodontal and systemic parameters included probing depth, bleeding on probing, clinical attachment level, hematologic parameters, as well as the following inflammatory markers: interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP), CD40 ligand, monocyte chemoattractant protein (MCP)-1, soluble P-selectin (sP-selectin), soluble vascular adhesion molecule (sVCAM)-1, and soluble intercellular adhesion molecule (sICAM)-1. Results: There were no differences in the hematologic parameters of the patients in the control and periodontal disease groups. Among the tested inflammatory markers, IL-6 concentrations were higher in the periodontal disease group at baseline compared to the controls (P=0.006). Therapy was highly effective (P<0.001 for all the analyzed clinical parameters), and a decrease in circulating IL-6 and hs-CRP concentrations was observed 3 months after therapy (P=0.001 and P=0.006, respectively). Our results also suggest that the CD40 ligand marker may have been different in the control and periodontal disease groups prior to the therapy (P=0.009). Conclusions: In apparently otherwise healthy patients, periodontal disease is associated with increased circulating concentrations of IL-6 and hs-CRP, which decreased 3 months after non-surgical periodontal therapy. With regard to the CD40 ligand, MCP-1, sP-selectin, sVCAM-1, and sICAM-1, no changes were seen in the periodontal disease group between baseline and 3 months after therapy. J Periodontol 2009;80:594-602.

A Research Agenda for Assessing the Potential Contribution of Genomic Medicine to Tobacco Control

This paper identifies research priorities in evaluating the ways in which "genomic medicine"-the use of genetic information to prevent and treat disease-may reduce tobacco-related harm by: (1) assisting more smokers to quit; (2) preventing non-smokers from beginning to smoke tobacco; and (3) reducing the harm caused by tobacco smoking. The method proposed to achieve the first aim is pharmacogenetics", the use of genetic information to optimise the selection of smoking-cessation programmes by screening smokers for polymorphisms that predict responses to different methods of smoking cessation. This method competes with the development of more effective forms of smoking cessation that involve vaccinating smokers against the effects of nicotine and using new pharmaceuticals (such as cannabinoid antagonists and nicotine agonists). The second and third aims are more speculative. They include: screening the population for genetic susceptibility to nicotine dependence and intervening (eg, by vaccinating children and adolescents against the effects of nicotine) to prevent smoking uptake, and screening the population for genetic susceptibility to tobacco-related diseases. A framework is described for future research on these policy options. This includes: epidemiological modelling and economic evaluation to specify the conditions under which these strategies are cost-effective; and social psychological research into the effect of providing genetic information on smokers' preparedness to quit, and the general views of the public on tobacco smoking.

Using household survey data to inform policy decisions regarding the delivery of evidence-based parenting interventions.

Background: This study used household survey data on the prevalence of child, parent and family variables to establish potential targets for a population-level intervention to strengthen parenting skills in the community. The goals of the intervention include decreasing child conduct problems, increasing parental self-efficacy, use of positive parenting strategies, decreasing coercive parenting and increasing help-seeking, social support and participation in positive parenting programmes. Methods: A total of 4010 parents with a child under the age of 12 years completed a statewide telephone survey on parenting. Results: One in three parents reported that their child had a behavioural or emotional problem in the previous 6 months. Furthermore, 9% of children aged 2–12 years meet criteria for oppositional defiant disorder. Parents who reported their child's behaviour to be difficult were more likely to perceive parenting as a negative experience (i.e. demanding, stressful and depressing). Parents with greatest difficulties were mothers without partners and who had low levels of confidence in their parenting roles. About 20% of parents reported being stressed and 5% reported being depressed in the 2 weeks prior to the survey. Parents with personal adjustment problems had lower levels of parenting confidence and their child was more difficult to manage. Only one in four parents had participated in a parent education programme. Conclusions: Implications for the setting of population-level goals and targets for strengthening parenting skills are discussed.

Methadone maintenance treatment reduces heroin injection in New South Wales prisons

The purpose of this study was to examine whether methadone maintenance treatment reduces injecting risk behaviour land therefore transmission of blood-borne viral infections) among prisoners in New South Wales (NSW), using comparison of retrospective reports of drug use in prisons for people who received standard drug treatment, time-limited methadone treatment and methadone maintenance treatment, The setting for the study was the NSW prison system. One hundred and eighty-five injecting drug users who had been recently released from NSW prisons were recruited in 1993, Self-reported drug use and injecting risk behaviour were compared in inmates who received standard drug treatment (counselling), time-limited methadone treatment and methadone maintenance treatment. HIV status was determined by serology, Intervention comprised high and low dose methadone treatment and counselling. The groups were similar in terms of most basic demographic characteristics but subjects who had been maintained on methadone reported a significantly lower prevalence of heroin injection, syringe sharing and scored lower on an HIV Risk-taking Behavioural Scale than subjects who received standard drug treatment and time-limited methadone treatment, This study suggests that methadone treatment is associated with reduced injecting risk behaviour in prison with adequate (greater than 60 mg) dose and duration in treatment. These treatment conditions are known to increase effectiveness in community-based methadone programmes. Prospective studies are required to evaluate the effectiveness of methadone programmes in the prevention of HIV and other blood-borne viral infections among IDU prisoners.

Injuries and noncommunicable diseases: emerging health problems of children in developing countries

The present article identifies, for children living in developing countries, the major causes of ill-health that are inadequately covered by established health programmes. Injuries and noncommunicable diseases, notably asthma, epilepsy, dental caries, diabetes mellitus and rheumatic heart disease, are growing in significance. In countries where resources are scarce it is to be expected that increasing importance will be attached to the development and implementation of measures against these problems. Their control may benefit from the application of elements of programmes directed against infectious, nutritional and perinatal disorders, which continue to predominate.

HIV risk behaviour and prevention in prison: a bleach programme for inmates in NSW

One hundred and eighty-one inmates in AIDS education courses were surveyed about their risk behaviour and access to disinfectants for syringe cleaning in 1993, Overall, 40% of respondents reported HIV risk behaviour in prison. One-quarter of respondents reported injecting, of whom three-quarters reported sharing syringes in prison. Most respondents who shared syringes reported cleaning them with disinfectants (96%), even though only one-third reported having easy access to disinfectants. One-sixth of respondents reported sharing tattooing equipment, of whom two-thirds reported using a disinfectant to clean the tattoo needle. Few respondents reported fellatio (8%) or anal intercourse (4%) in prison. Although some respondents faced difficulty in obtaining disinfectants, almost all respondents cleaned syringes with bleach when sharing. High levels of risk behaviour in prison might be reduced by methadone maintenance and condom programmes. A trial of strict one-for-one syringe exchange warrants consideration.

Tuberculosis and health sector reform: experience of integrating tuberculosis services into the district health system in rural South Africa

SETTING: Hlabisa health district, South Africa. OBJECTIVE: To describe the integration of a vertical tuberculosis control programme into an emerging 'horizontal' district health system, within the context of health sector reform. DESIGN: Descriptive account of the process of integration of the programme into the health system. RESULTS: A highly 'vertical' system of delivering tuberculosis treatment (with poor programme outcomes) was converted into a (horizontal' team, integrated within the district health system, that used available resources such as village clinics and community health workers, with improved programme outcomes. CONCLUSIONS: In some settings at least, integration of tuberculosis 'programmes' into the district health system as tuberculosis 'teams' is feasible, and may produce highly cost-effective outcomes.

Who fails to complete tuberculosis treatment? Temporal trends and risk factors for treatment interruption in a community-based directly observed therapy programme in a rural district of South Africa

SETTING: Hlabisa Tuberculosis Programme, Hlabisa, South Africa. OBJECTIVE: To determine trends in and risk factors for interruption of tuberculosis treatment. METHODS: Data were extracted from the control programme database starting in 1991. Temporal trends in treatment interruption are described; independent risk factors for treatment interruption were determined with a multiple logistic regression model, and Kaplan-Meier survival curves for treatment interruption were constructed for patients treated in 1994-1995. RESULTS: Overall 629 of 3610 surviving patients (17%) failed to complete treatment; this proportion increased from 11% (n = 79) in 1991/1992 to 22% (n = 201) in 1996. Independent risk factors for treatment interruption were diagnosis between 1994-1996 compared with 1991-1393 (odds ratio [OR] 1.9, 95% confidence interval [CT] 1.6-2.4); human immunodeficiency virus (HIV) positivity compared with HIV negativity (OR 1.8, 95% CI 1.4-2.4); supervised by village clinic compared with community health worker (OR 1.9, 95% CI 1.4-2.6); and male versus female sex (OR 1.3, 95% CI 1.1-1.6). Few patients interrupted treatment during the first 2 weeks, and the treatment interruption rate thereafter was constant at 1% per 14 days. CONCLUSIONS: Frequency of treatment interruption from this programme has increased recently. The strongest risk factor was year of diagnosis, perhaps reflecting the impact of an increased caseload on programme performance. Ensuring adherence to therapy in communities with a high level of migration remains a challenge even within community-based directly observed therapy programmes.

Public health implications of new guidelines for lead in drinking water: a case study in an area with historically high water lead levels

Concern about the neurotoxicity of lead, particularly in infants and young children, has led to a revision of blood lead levels which are considered to involve an acceptable level of human exposure. Drinking water guidelines have also been reviewed in order to reduce this source of population exposure to lead. In the last 20 years, guidelines have been reduced from 100 to 50 to 10 mu g/litre. Lead in tap water used to be a major public health problem in Glasgow because of the high prevalence of houses with lead service pipes, the low pH of the public water supply and the resulting high levels of lead in water used for public consumption. Following two separate programmes of water treatment, involving the addition of lime and, a decade later, lime supplemented with orthophosphate, it is considered that maximal measures have been taken to reduce lead exposure by chemical treatment of the water supply. Any residual problem of public exposure would require large scale replacement of lead service pipes. In anticipation of the more stringent limits for lead in drinking water, we set out to measure current lead exposure From tap water in the population of Glasgow served by the Loch Katrine water supply. to compare the current situation with 12 years previously and to assess the public health implications of different limits. The study was based on mothers of young children since maternal blood lead concentrations and the domestic water that mothers use to prepare bottle feeds are the principal sources of foetal and infant lead exposure. An estimated 17% of mothers lived in households with tap water lead concentrations of 10 mu g/litre (the WHO guideline) or above in 1993 compared with 49% in 1981. Mean maternal blood lead concentrations fell by 69% in 12 years. For a given water lead concentration, maternal blood lead concentrations were 67% lower. The mean maternal blood lead concentration was 3.7 mu g/litre in the population at large, compared with 3.3 mu g/litre in households with negligible or absent tap water lead. Nevertheless, between 63% and 76% of cases of mothers with blood lead concentrations of 10 mu g/dl or above were attributable to tap water lead. The study found that maternal blood lead concentrations were well within limits currently considered safe for human health. About 15% of infants may be exposed via bottle feeds to tap water lead concentrations that exceed the WHO guideline of 10 mu g/litre. In the context of the health and social problems which affect the well-being and development of infants and children in Glasgow, however, current levels of lend exposure are considered to present a relatively minor health problem. (C) 2000 Elsevier Science Ltd. All rights reserved.

Naltrexone in the treatment of male alcoholics - an effectiveness study in Singapore

Naltrexone has been demonstrated in western studies to be a useful pharmacological adjunct within treatment programmes for alcoholic patients. We report the first study of its efficacy and usefulness in an Asian region. This project was designed to allow naltrexone's performance to be assessed under routine clinical conditions but with patients selected on the basis of their being likely to comply. Following in-patient detoxification, 53 male alcohol-dependent patients admitted to the Alcohol Treatment Centre at Woodbridge Hospital, Singapore, were enrolled in a 12-week, placebo-controlled trial of naltrexone hydrochloride (50 mg/day). Subjects were randomized on a 2:1 basis, with 35 receiving naltrexone and 18 receiving placebo. Analyses identified that a higher percentage of naltrexone patients completed the study (40% vs. 22%). In the study non-completers, the dropout rate due to drinking relapse was also lower in the naltrexone group (9% vs. 43%). Of the 39 patients for whom drinking status over the trial could be ascertained, fewer naltrexone-treated patients drank (33% vs. 53%). Alcohol craving scores also showed a selective and distinct reduction in the naltrexone-treated group. Results suggest that naltrexone may be an effective and safe aid to treatment of alcohol dependent patients in Asian patients, for whom the aims are to reduce alcohol craving and drinking reinstatement, but where compliance is likely to be low.

An overview of diversion strategies for Australian drug-related offenders

This paper provides a descriptive overview of options for diversion of drug-related offenders from the criminal justice system. Drug-related offences include drug offences (for example, possession of a prohibited substance); offences that are directly linked to intoxication (for example, drink-driving or assault); and offences committed to support drug use (for example, theft). After an offence has been detected by police, multiple opportunities for diversion occur throughout the criminal justice process. (a) Pre-arrest: when an offence is first detected, prior to a charge being laid. This is known as police diversion and includes fines, warnings and cautions, sometimes with educational information or referral to assessment and treatment. (b) Pre-trial: when a charge is made but before the matter is heard at court. Examples are treatment as a condition of bail, conferencing and prosecutor discretion. (c) Pre-sentence: a delay of sentence while assessment and treatment are sought. (d) Post-sentence: as part of sentencing, for example suspended sentences, drug courts, noncustodial sentences and circle sentencing. (e) Pre-release: prior to release from a sentence, on parole. Issues for diversion programmes include net widening, the ethics of coercion to treatment, the needs of families and intersectoral collaboration. A framework for diversion is presented in which increasingly treatment-focused and coercive diversion strategies are used as offenders' criminal careers and drug problems increase.

Neointimal formation by circulating bone marrow cells

The origin of smooth muscle cells involved in vascular healing was examined. Eighteen C57BL/6 (Ly 5.2) female mice underwent whole body irradiation followed by transfusion with 10(6) bone nucleated marrow cells from congenic (Ly 5.1) male donors. Successful repopulation by donor marrow was demonstrated after 4 weeks by flow cytometry with FITC-conjugated A20.1/Ly 5.1 monoclonal antibody. The iliac artery of six of the chimeric mice was scratch-injured by five passes of a probe, causing severe medial damage. After 4 weeks the arterial lumen was obliterated by a cell-rich neointima, with alpha-smooth muscle actin-containing cells present around the residual lumen. Approximately half of these cells were of male donor origin, as evidenced by in situ hybridization with a Y chromosome-specific probe. An organized arterial thrombus was formed in the remaining 12 chimeric mice by inserting an 8.0 silk suture into the left common carotid artery. Donor cells staining with alpha-smooth muscle actin were found in those arteries sustaining serious damage but not in arteries with minimal damage. Our results suggest that bone marrow-derived cells are recruited in vascular healing as a complementary source of smooth muscle-like cells when the media is severely damaged and few resident smooth muscle cells are available to effect repair.

Undergraduate student experience in dental service delivery in rural South Australia: An analysis of costs and benefits

Background, Rural experience for dental students can provide valuable clinical education, change attitudes to rural practice, and make a valuable contribution to clinical service provision. The aim of this paper is to assess the costs and benefits of service delivery by students through rural training programmes Methods: Groups of two students worked in the public dental clinics in adjacent rural centres where there had been long-term difficulties in recruiting staff. The costs and benefits of the programme were assessed by the impact on waiting lists, the total cost per patient of, a course of care and by the marginal cost of adding service provision by students to existing arrangements. Results: The total costs of emergency and complete treatment provided by students were greater than the costs of treatment provided by public-sector dentists but less than the costs of private providers treating public patients. However, the value of services were greater when care was provided by students or private providers and the marginal cost of students providing services was 50-70 per cent of the cost of care provided by public dentists. Conclusion: This assessment suggests that the service benefits achieved compliment the primary objective of influencing the attitude of students to rural practice.

Altered kinetics and benzodiazepine sensitivity of a GABA(A) receptor subunit mutation [gamma(2)(R43Q)] found in human epilepsy

The gamma-aminobutyric acid type A (GABA(A)) receptor mediates fast inhibitory synaptic transmission in the CNS. Dysfunction of the GABA(A) receptor would be expected to cause neuronal hyperexcitability, a phenomenon linked with epileptogenesis. We have investigated the functional consequences of an arginine-to-glutamine mutation at position 43 within the GABA(A) gamma(2)-subunit found in a family with childhood absence epilepsy and febrile seizures. Rapid-application experiments performed on receptors expressed in HEK-293 cells demonstrated that the mutation slows GABA(A) receptor deactivation and increases the rate of desensitization, resulting in an accumulation of desensitized receptors during repeated, short applications. In Xenopus laevis oocytes, two-electrode voltage-clamp analysis of steady-state currents obtained from alpha(1)beta(2)gamma(2) or alpha(1)beta(2)gamma(2)(R43Q) receptors did not reveal any differences in GABA sensitivity. However, differences in the benzodiazepine pharmacology of mutant receptors were apparent. Mutant receptors expressed in oocytes displayed reduced sensitivity to diazepam and flunitrazepam but not the imiclazopyricline zolpidem. These results provide evidence of impaired GABA(A) receptor function that could decrease the efficacy of transmission at inhibitory synapses, possibly generating a hyperexcitable neuronal state in thalamocortical networks of epileptic patients possessing the mutant subunit.