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Biomedical subjects

Paul Farmer

Publications and source records attributed to Paul Farmer.

At least 19 recordsLinked to original sources
PubMed2006

Tungiasis in rural Haiti: a community-based response.

Tungiasis is a disease endemic to poor communities in Latin America, the Caribbean and Africa. It is caused by the female flea, Tunga penetrans, which burrows into the skin of its host to feed while producing and extruding eggs. Consequent lesions may be painful and even crippling with damage ranging from mild erythema and swelling to necrosis. Superinfection of lesions can be serious and may result in auto-amputation or death from tetanus. We describe an outbreak of tungiasis in rural Haiti and a community-based intervention used to address it. Of 177 patients assessed, 132 (47 female, 85 male, 23 children) had tungiasis lesions. Forty-four patients had clinical signs of superinfection; 15 had ectopic lesions. Community health workers cleaned and disinfected patients' feet and any parts of the body with ectopic lesions, and then extracted fleas from existing lesions. Patients with superinfections were treated with appropriate antibiotics. Over 1000 pairs of shoes were distributed in the villages. Over 400 adults were given tetanus vaccinations during follow-up visits. Patients who had been treated reported feeling better and those who had received shoes indicated they had not developed new lesions. All superinfections were resolved. We concluded that community-based care can treat tungiasis effectively.

Adolescent↗
PubMed2006

A novel training model to address health problems in poor and underserved populations.

Health disparities are increasingly common and many U.S. practitioners have informal experience working in resource-poor settings. There are, however, few graduate medical education programs that focus on health equity. A graduate medical education program in health equity was developed at Brigham and Women's Hospital based on a review of existing literature and on a survey of junior faculty who have had informal health disparities experience. The Howard Hiatt Residency in Global Health Equity and Internal Medicine was developed as a four-year program to provide intensive training in internal medicine and health disparities. Participating residents are matched with a mentor who has clinical and research experience in the field of global health. In addition to a series of didactic teaching sessions and longitudinal seminars that focus on issues of global health equity, residents take graduate level courses in epidemiology, health policy, ethics, and medical anthropology. Residents also carry out an independent research project in a geographic area that suffers from health disparities. Two residents are selected for training per year. Participating faculty are multidisciplinary and come from diverse Harvard-affiliated institutions. Graduate medical education in the United States with a focus on health equity is lacking. It is hoped that the novel training program in health equity for internal medical residents developed at Brigham and Women's Hospital can serve as a model for other teaching hospitals based in the United States.

Curriculum↗
PubMed2005

Cytoskeletal remodeling in vascular smooth muscle cells in response to angiotensin II-induced activation of the SHP-2 tyrosine phosphatase.

Angiotensin II is an octapeptide that regulates diverse cellular responses including the actin cytoskeletal organization. In this study, stable cell lines overexpressing wild-type or catalytically inactive SHP-2 were employed to elucidate the signaling pathway utilized by the SHP-2 tyrosine phosphatase that mediates an angiotensin II-induced reorganization of the actin cytoskeleton in vascular smooth muscle cells (VSMC). The expression of wild-type SHP-2 prevented an angiotensin II dependent increase in stress fiber formation. In contrast, the catalytically inactive mutant SHP-2 increased stress fiber formation. Additional observations further established that SHP-2 regulates the reorganization of the actin cytoskeleton through RhoA- and Vav2-dependent signaling pathways. The expression of wild-type SHP-2 caused a dephosphorylation of several focal adhesion associated proteins including paxillin, p130Cas, and tensin in VSMC. This dephosphorylation of focal adhesion associated proteins was accompanied by significantly decreased numbers of focal adhesions within cells. These results demonstrate a unique role for SHP-2 in the regulation of the cellular architecture of VSMC, suggesting the possibility that this phosphatase might be instrumental in vascular remodeling.

Actins↗
PubMed2005

Limited good and limited vision: multidrug-resistant tuberculosis and global health policy.

Almost a third of the world's population is infected with Mycobacterium tuberculosis, the organism that causes tuberculosis disease. Most of those infected never fall ill, but individuals who do can recover if they have access to effective therapies. This paper discusses certain ethical and ethnographic issues raised by cases in which patients are infected with M. tuberculosis strains resistant to at least the two most powerful drugs on which therapy is usually based. In most poor countries, people with such multidrug-resistant tuberculosis (MDR-TB) were, until very recently, considered "untreatable." In addition to being consigned to a permanent state of ill health, they were also at risk of transmitting their resistant strain to others. In this paper we discuss the logic of "cost-effectiveness," which international health policy-makers utilized to make the case that treatment of MDR-TB is not feasible in resource poor settings. These analyses, which have held sway in public health policy for many years, are flawed, we argue, because they ignore and conceal the social determinants of access to health services and often rely on assumptions rather than evidence. We propose that policies based solely on analyses of cost-effectiveness of specific interventions for individual settings can be short-sighted and, because they do not pay sufficient attention to the social, political, economic, epidemiological and pathophysiological factors influencing the production of health, will ultimately hinder progress toward effective global TB control.

Cost-Benefit Analysis↗
PubMed2005

Active ingredients in anti-stigma programmes in mental health.

This paper draws upon a review of the relevant literature and the results of the recent Mental Health Awareness in Action (MHAA) programme in England to discuss the current evidence base on the active ingredients in effective anti-stigma interventions in mental health. The MHAA Programme delivered educational interventions to 109 police officers, 78 adults from different community groups whose working lives involved supporting people with mental health problems but who had received no mental health training and 472 schools students aged 14-15. Each adult target group received two intervention sessions lasting two hours. The two school lessons were 50 minutes each. Knowledge, attitudes and behavioural intent were assessed at baseline and follow-up. In addition focus groups were held with mental health service users to explore the impact of stigma on their lives and facilitators of educational workshops were interviewed to provide expert opinion on 'what works' to reduce psychiatric stigma. Personal contact was predictive of positive changes in knowledge and attitudes for the school students but not the police officers or community adult group. The key active ingredient identified by all intervention groups and workshop facilitators were the testimonies of service users. The statements of service users (consumers) about their experience of mental health problems and of their contact with a range of services had the greatest and most lasting impact on the target audiences in terms of reducing mental health stigma.

Adolescent↗
PubMed2005

Understanding and addressing AIDS-related stigma: from anthropological theory to clinical practice in Haiti.

For the past several years, diverse and often confused concepts of stigma have been invoked in discussions on AIDS. Many have argued compellingly that AIDS-related stigma acts as a barrier to voluntary counseling and testing. Less compelling are observations regarding the source of stigma or its role in decreasing interest in HIV care. We reviewed these claims as well as literature from anthropology, sociology, and public health. Preliminary data from research in rural Haiti suggest that the introduction of quality HIV care can lead to a rapid reduction in stigma, with resulting increased uptake of testing. Rather than stigma, logistic and economic barriers determine who will access such services. Implications for scale-up of integrated AIDS prevention and care are explored.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Integration of the NfkappaB p65 subunit into the vitamin D receptor transcriptional complex: identification of p65 domains that inhibit 1,25-dihydroxyvitamin D3-stimulated transcription.

Resistance to the action of vitamin D (D) occurs in response to tumor necrosis factor-alpha (TNF-alpha), an effect mediated by nuclear factor kappa B (NfkappaB). To determine the mechanism of NfkappaB inhibition of D-stimulated transcription, chromatin immunoprecipitation assays (CHIP) were done in osteoblastic ROS 17/2.8 cells that had been treated with TNF-alpha or transfected with the p65 subunit of NfkappaB. These treatments caused stable incorporation of p65 into the transcription complex bound to the vitamin D response element (VDRE) of the osteocalcin promoter. Deletion analysis of p65 functional domains revealed that the p65 N-terminus and a midmolecular region were both required for the inhibitory action of p65. Pull-down assays were done using an immobilized glutathione S-transferase (GST)-VDR fusion protein to study the effect of p65 on VDR binding to steroid coactivator-1 (SRC-1), a major D-dependent coactivator. p65 inhibited VDR-SRC-1 binding in a dose-dependent manner. Mutations of p65 that abrogated the inhibitory effect on D-stimulated transcription also failed to inhibit VDR-SRC-1 binding. The inhibitory effect of p65 on VDR transactivation was not due to recruitment of a histone deacetylase (HDAC), since inhibition was not relieved by the HDAC inhibitors sodium butyrate or trichostatin A. Overexpression of SRC-1 or the general coactivators, Creb binding protein or SRC-3, also failed to relieve p65 inhibition of transcription. In addition, Chip assays revealed that TNF-alpha treatment prevented D recruitment of SRC-1 to the transcription complex. These results show that TNF-alpha inhibition of vitamin D-action includes stable integration of p65 in the VDR transcription complex. Once anchored to proteins within the complex, p65 disrupts VDR binding to SRC-1, thus decreasing the efficiency of D-stimulated gene transcription.

Calcitriol↗
PubMed2004

Programmes and principles in treatment of multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB) presents an increasing threat to global tuberculosis control. Many crucial management issues in MDR-TB treatment remain unanswered. We reviewed the existing scientific research on MDR-TB treatment, which consists entirely of retrospective cohort studies. Although direct comparisons of these studies are impossible, some insights can be gained: MDR-TB can and should be addressed therapeutically in resource-poor settings; starting of treatment early is crucial; aggressive treatment regimens and high-end dosing are recommended given the lower potency of second-line antituberculosis drugs; and strategies to improve treatment adherence, such as directly observed therapy, should be used. Opportunities to treat MDR-TB in developing countries are now possible through the Global Fund to Fight AIDS, TB, and Malaria, and the Green Light Committee for Access to Second-line Anti-tuberculosis Drugs. As treatment of MDR-TB becomes increasingly available in resource-poor areas, where it is needed most, further clinical and operational research is urgently needed to guide clinicians in the management of this disease.

Antibiotics, Antitubercular↗
PubMed2004

Selective down-regulation of angiotensin II receptor type 1A signaling by protein tyrosine phosphatase SHP-2 in vascular smooth muscle cells.

The heptahelical AT(1) G-protein-coupled receptor lacks inherent tyrosine kinase activity. Angiotensin II binding to AT(1) nevertheless activates several tyrosine kinases and stimulates both tyrosine phosphorylation and phosphatase activity of the SHP-2 tyrosine phosphatase in vascular smooth muscle cells. Since a balance between tyrosine kinase and tyrosine phosphatase activities is essential in angiotensin II signaling, we investigated the role of SHP-2 in modulating tyrosine kinase signaling pathways by stably transfecting vascular smooth muscle cells with expression vectors encoding wild-type SHP-2 protein or a catalytically inactive SHP-2 mutant. Our data indicate that SHP-2 is an efficient negative regulator of angiotensin II signaling. SHP-2 inhibited c-Src catalytic activity by dephosphorylating a positive regulatory tyrosine 418 within the Src kinase domain. Importantly, SHP-2 expression also abrogated angiotensin II-induced activation of ERK, whereas expression of catalytically inactive SHP-2 caused sustained ERK activation. Thus, SHP-2 likely regulates angiotensin II-induced MAP kinase signaling by inactivating c-Src. These SHP-2 effects were specific for a subset of angiotensin II signaling pathways, since SHP-2 overexpression failed to influence Jak2 tyrosine phosphorylation or Fyn catalytic activity. These data show SHP-2 represents a critical negative regulator of angiotensin II signaling, and further demonstrate a new function for this phosphatase in vascular smooth muscle cells.

Animals↗
PubMed2004

Community-based treatment of multidrug-resistant tuberculosis in Lima, Peru: 7 years of experience.

Programs implementing community-based directly observed therapy (DOT) have demonstrated success in the treatment of patients with tuberculosis. However, given complexities in the management and treatment of patients infected with multidrug-resistant tuberculosis (MDR-TB), the utilization of community-based DOT to treat MDR-TB patients has only recently been successfully attempted. We describe the first such program and highlight the crucial components and most critical challenges to creating a successful community-based MDR-TB treatment program.

Community Health Services↗
PubMed2004

Rethinking medical ethics: a view from below.

In this paper, we argue that lack of access to the fruits of modern medicine and the science that informs it is an important and neglected topic within bioethics and medical ethics. This is especially clear to those working in what are now termed 'resource-poor settings'- to those working, in plain language, among populations living in dire poverty. We draw on our experience with infectious diseases in some of the poorest communities in the world to interrogate the central imperatives of bioethics and medical ethics. AIDS, tuberculosis, and malaria are the three leading infectious killers of adults in the world today. Because each disease is treatable with already available therapies, the lack of access to medical care is widely perceived in heavily disease-burdened areas as constituting an ethical and moral dilemma. In settings in which research on these diseases are conducted but there is little in the way of therapy, there is much talk of first world diagnostics and third world therapeutics. Here we call for the 'resocialising' of ethics. To resocialise medical ethics will involve using the socialising disciplines to contextualise fully ethical dilemmas in settings of poverty and, a related gambit, the systematic participation of the destitute sick. Clinical research across steep gradients also needs to be linked with the interventions that are demanded by the poor and otherwise marginalised. We conclude that medical ethics must grapple more persistently with the growing problem posed by the yawning 'outcome gap' between rich and poor.

Bioethics↗
PubMed2004

New malaise: bioethics and human rights in the global era.

Recent transnational HIV research projects have raised questions about the ethics of research in developing countries, and with good reason. Lower ethical standards are often applied in these settings, yet the field of bioethics has remained relatively quiet on the subject, concerning itself primarily with issues that only affect affluent countries. Here we call for a new focus on equity and human rights in bioethics.

Bioethics↗