Domestic poultry-raising practices in a Peruvian shantytown: implications for control of Campylobacter jejuni-associated diarrhea

Raising poultry at home is common in many periurban communities in low-income countries. Studies demonstrate that free-range domestic poultry increase children's risk of infection with diarrhea-causing organisms such as Campylobacter jejuni. Corralling might reduce risk, but research on the socioeconomic acceptability of corralling is lacking. To explore this issue, we studied local knowledge and practices related to poultry-raising in a Peruvian shantytown. Our objectives were to understand: (1). motives for raising domestic poultry; (2). economic and cultural factors that affect the feasibility of corralling; and (3). local perceptions about the relationship between domestic poultry and disease. During 1999-2000, we met with community health volunteers and conducted ethnographic and structured interviews with residents about poultry-raising practices. We then enrolled 12 families in a 2-month trial of corral use during which field workers made biweekly surveillance visits to each family. Most participants reported that they raise birds because home-grown poultry and eggs taste better and are more nutritious and because they enjoy living around animals. Some want to teach their children about raising animals. To prevent theft, many residents shut their birds in provisional enclosures at night, but most stated that birds are healthier, happier, and produce better meat and eggs when let loose by day. Many view bird feces in the house and yard as dirty, but few see a connection to illness. Residents consider chicks and ducklings more innocuous than adult birds and are more likely to allow them inside the house and permit children to play with them. After extensive orientation and technical assistance, participants were willing to corral birds more often. But due to perceived disadvantages, many kept birds penned only intermittently. Additional food and water costs were a significant obstacle for some. Adequate space, bird care and corral hygiene would also need to be addressed to make this intervention viable. Developing a secure, acceptable and affordable corral remains a challenge in this population.     

High Rates of Sex with Men among High-Risk,Heterosexually-Identified Men in Low-Income,Coastal Peru

In this paper we describe sex with men, including the frequency of sex and unprotected sex, among high-risk, heterosexually-identified men in urban, low-income, coastal Peru. During 2001–2002, a random community-based sample of these men was administered an epidemiologic survey collecting sexual risk behavior data. Among the 924 high-risk heterosexually-identified men, 131 (14.2%) reported at least one male partner in the past 6 months. Of these, 113 (86.3%) reported male and female partners and among those with partners of both sexes, 84.2% and 57.0% of sex acts with female and male partners, respectively, were unprotected, (RR 1.48, 95% CI = 1.31–1.68). We observed a high rate of recent bisexual behavior compared to past studies showing frequent, unprotected sex with male and female partners. This population has substantial potential to act as a bridge population between and their male and female partners and should be addressed by prevention programs. Previously published abstract: Konda, K.A., Fernandez, P. Klausner, J.D., Lescano, A.G., Leon, S.R., Caceres, C.F., and Coates, T.J. (2005). Heterosexually identified, socially marginalized men who report recent sex with men in Peru. In: Abstracts of the 16th biennial International Society for Sexually Transmitted Diseases Research (ISSTDR) (Amsterdam, Netherlands), MP-172.     

Effects of irbesartan and perindopril on forearm reactive hyperemia and inflammatory process, in normotensive patients with coronary artery disease

Cardiovascular disease is a major global cause of mortality, and its fundamental underlying substrate is atherosclerosis. Young and old patients have different risk factor profiles, clinical presentations, angiographic findings and prognosis. We performed a retrospective case-control study in a cohort (cases) of premature coronary disease (45 years, n=200). The proportion of premature coronary disease in our geographic area was 9%. The average age of the case group was 41 and 64 years in controls (p<0.001). The male sex, though majority in both groups, was significantly more prevalent in the young group (92.5%) than in the older group (76.0%, p<0.001). The presence of smoking habit, hyperlipidemia and family history was significantly higher in the case group as well, with smoking habit being the most prevalent risk factor. In contrast, hypertension and diabetes were more frequent in controls. The number of affected vessels in cases was significantly less than the control group (1.4+/-0.8 vs. 1.7+/-0.9; p=0.013). Premature coronary disease affects predominantly the male sex and shows high prevalence of cardiovascular risk factors, mainly tobacco, hyperlipidemia, and family history of ischemic heart disease. In addition, it is characterised by a less extensive coronary atherosclerosis, mainly with the higher presence of single-vessel disease in contrast to older patients, as well as lower initial mortality.     

Identification of synovial biomarkers of response to experimental treatment in early‐phase clinical trials in spondylarthritis

Objective

To identify biomarkers for effective treatment in early‐phase clinical trials of spondylarthritis (SpA), by analyzing which synovial features can be reliably identified in patients with SpA.

Methods

Synovial biopsies were performed at weeks 0 and 12 in 20 SpA patients treated with infliximab, 20 treated with etanercept, and 12 who were not treated. Primary clinical outcome measures were patient and physician global assessment of disease activity. Extensive histologic evaluation included assessment of lining layer hyperplasia, vascularity, markers of cellular infiltration, and metalloproteinases (MMPs) in the lining and sublining layers.

Results

Changes in levels of CD163 (resident tissue macrophages) in the lining, and CD163, MMP‐3, and myeloid‐related protein 14 (MRP‐14; infiltrating myeloid cells) in the sublining correlated significantly with changes in the primary clinical outcomes. Comparison between responders (n = 35) and nonresponders (n = 17) showed differences in the degree of change in the levels of CD163 in the lining and CD163, MMP‐3, and CD3 in the sublining, whereas trends in change in the levels of MRP‐8 and MRP‐14 in the lining and sublining were similar in the 2 groups. Accordingly, the highest differences in standardized response means (SRMs) between the 2 groups were found for CD163 in the lining, MMP‐3, CD163, CD3, and MRP‐8 in the sublining, and the level of polymorphonuclear cells (PMNs). When comparing treated and untreated patients, high differences in SRMs were again found for CD163 in the lining, MMP‐3, CD163, and MRP‐8 in the sublining, and PMNs. These parameters performed prognostically as well as the erythrocyte sedimentation rate and better than the C‐reactive protein level. Class prediction analysis yielded a 90% correct prediction using 8 synovial parameters, as follows: lining and sublining CD163, MRP‐8, and MRP‐14, sublining MMP‐3, and PMNs. In validation analyses with independent samples, effective treatment was correctly predicted in 24 of 30 SpA patients and in 2 of 2 placebo‐treated patients.

Conclusion

Changes in synovial macrophage subsets, PMN levels, and MMP‐3 expression reflect response to treatment in SpA. The ability of these parameters to correctly identify effective therapy makes them interesting biomarkers for use in early‐phase clinical trials in SpA.

     

Involvement of matrix metalloproteinases and their inhibitors in peripheral synovitis and down‐regulation by tumor necrosis factor α blockade in spondylarthropathy

Objective

To investigate the role of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in spondylarthropathy (SpA) synovitis.

Methods

Paired samples of synovial biopsy tissue as well as serum and synovial fluid (SF) from 41 patients with SpA and 20 patients with rheumatoid arthritis (RA) and serum samples from 20 healthy controls were analyzed by immunohistochemistry and enzyme‐linked immunosorbent assay for the presence of MMPs 1, 2, 3, and 9 and TIMPs 1 and 2. In addition, sera from 16 patients with ankylosing spondylitis (AS) and peripheral synovitis and 17 patients with AS and exclusively axial involvement were analyzed. An additional cohort of SpA patients was analyzed at baseline and after 12 weeks of infliximab treatment.

Results

Staining for MMPs and TIMPs showed a cellular and interstitial pattern in the synovial lining and sublining layers that was similar between the RA and SpA patients. Involvement of MMPs and TIMPs in SpA synovitis was suggested by the correlation with cellular infiltration, vascularization, and cartilage degradation. Higher serum levels of MMPs 3 and 9 were revealed in SpA and RA patients as compared with healthy controls. Production of MMP‐3, but not MMP‐9, in the serum reflected the presence of peripheral synovitis, as indicated by 1) the correlation between serum levels, SF levels (which were 1,000‐fold higher than the serum levels), and synovial expression of MMP‐3, 2) the increased levels of MMP‐3 in AS patients with peripheral disease and not exclusively axial involvement, and 3) the correlation of serum and SF MMP‐3 with parameters of synovial, but not systemic, inflammation. The modulation of the MMP/TIMP system by tumor necrosis factor α (TNFα) blockade was confirmed by the down‐regulation of all MMPs and TIMPs in the synovium and a pronounced and rapid decrease of serum MMP‐3.

Conclusion

MMPs and TIMPs are highly expressed in SpA synovitis and mirror both the inflammatory and tissue‐remodeling aspects of the local disease process. Serum MMP‐3, originating from the inflamed joint, represents a valuable biomarker for peripheral synovitis. Modulation of the MMP/TIMP system by infliximab could contribute to the antiinflammatory and tissue‐remodeling effects of TNFα blockade in SpA.

     

Inflammatory bowel disease-related dysplasia and cancer: A referral center study in northwestern Greece

BACKGROUND: An increased risk of colorectal cancer in ulcerative colitis (UC) and Crohn's disease (CD) has been reported. No data on inflammatory bowel disease (IBD)-related dysplasia and cancer is available in Greece, where the disease profile seems to be milder than that of northern Europe. METHODS: A study was conducted of 215 IBD patients (182 with UC, 33 with CD) from a referral center. Patients were followed up for 3-18 years. The prevalence of cancer and dysplasia among the IBD patients who were diagnosed in northwestern Greece was analyzed and registered. Statistical analysis was performed assuming that this IBD cohort had the same risk of developing malignancies as the general population in Greece. RESULTS: Six of the 215 patients in this IBD cohort had cancer, and 20 of 126 patients for whom bowel biopsies were available had dysplasia. Three of these cases were high-grade dysplasia. There was no significant difference in the numbers of calculated and expected cases of IBD-related cancer at any sites except for the skin [2.7 vs. 2.0]. CONCLUSIONS: This IBD cohort did not appear to have an increased risk of cancer during the time period studied. It would be interesting to re-assess the risk after the second and third decades of follow-up.     

Echocardiographic Imaging of Right Ventricular Outflow Obstruction During Chemotherapy of Mediastinal Lymphoma

Transthoracic echocardiography is a versatile method for imaging cardiac complications caused by mediastinal tumors. Especially, the response to therapeutic measures can be assessed promptly. We present echocardiographic imaging of the regression of right ventricular outflow tract obstruction by chemotherapy.     

Vitamin D receptor activation and prevention of arterial ageing

In chronic kidney disease (CKD) patients, cardiovascular (CV) morbidity and mortality rate is higher than in the general population, because of frequently concomitant hypertension, peripheral vascular disease, heart failure, vascular calcification (VC), diabetes and mineral bone disease. Recently, another important factor associated to CV risk in CKD has been deeply investigated: vitamin D deficiency. Vitamin D Receptors (VDRs) are present in several systems and tissues and VDR activation is associated to positive effects, resulting in better blood pressure control and prevention of diabetic nephropathy. Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA), calcitriol, is associated to higher serum calcium and phosphate levels, thus worsening CV risk in CKD. Recent data showed that the selective VDRA paricalcitol might have ameliorative CV effects. The potential positive impact of the use of paricalcitol on diabetic nephropathy, cardiac disease, hypertension, and VC may open new paths in the fight against CV disease in CKD patients.     

Characteristic epitope recognition pattern of autoantibodies against eukaryotic ribosomal protein L7 in systemic autoimmune diseases

Objective. To define the epitope-recognition pattern and the fine specificity of the autoantibody response to protein L7 in patients with rheumatic diseases. Methods. The epitope-recognition pattern was studied by enzyme-linked immunosorbent assay utilizing overlapping fragments of L7. The fine specificity was examined by binding inhibition and isoelectric focusing. Results. We observed a disease-specific epitope-recognition pattern of anti-L7 autoantibodies. There was one immunodominant epitope that was recognized by all anti-L7-positive sera from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc). Additional recognition of minor epitopes was observed; it arises by intramolecular epitope spreading and was correlated with disease activity in SLE patients. SSc patients differed from SLE and RA patients in that their sera did not recognize certain minor epitopes. The major epitope was recognized by high-affinity autoantibodies of limited heterogeneity. Minor epitopes were recognized by heterogeneous low-affinity autoantibodies. Conclusion. The anti-L7 autoantibody response is oligoclonal. Additional B cell clones are activated by antigen during active phases of disease.     

Randomized double‐blind comparison of chimeric monoclonal antibody to tumor necrosis factor α (infliximab) versus placebo in active spondylarthropathy

Objective

To confirm in a placebo‐controlled trial the safety and efficacy profile of infliximab in short‐term treatment of patients with active spondylarthropathy (SpA).

Methods

Forty patients with active SpA were randomly assigned to receive an intravenous loading dose (weeks 0, 2, and 6) of 5 mg/kg infliximab or placebo. Evaluations for efficacy and safety were performed at weeks 1, 2, 6, 8, and 12. The primary end points of this study were the improvements in patient and physician global assessments of disease activity on a 100‐mm visual analog scale.

Results

Both primary end points improved significantly in the infliximab group compared with the baseline value, with no improvement in the placebo group. As early as week 2 and sustained up to week 12, there was a highly statistically significant difference between the values for these 2 end points in the infliximab versus the placebo group. In most of the other assessments of disease activity (laboratory measures, assessments of specific peripheral and/or axial disease), significant improvements were observed in the infliximab group compared with the baseline value and compared with placebo. Minor adverse events not causing discontinuation were equally observed in both treatment groups. There was one severe drug‐related adverse event, in which a patient developed disseminated tuberculosis.

Conclusion

Tumor necrosis factor α blockade with infliximab in patients with active SpA was well tolerated and resulted in significant clinical and laboratory improvements in this short‐term, placebo‐controlled study. However, the occurrence of tuberculosis in one patient necessitates strict inclusion criteria and long‐term followup.