The effect of lifestyle and risk factor modification on occlusive peripheral arterial disease outcomes: standard healthcare vs structured programme-for a randomised controlled trial protocol.

BACKGROUND: Peripheral arterial disease (PAD) affects more than 200 million of the global population. PAD represents a marker for premature cardiovascular events. Patients with PAD, even in the absence of a history of myocardial infarction or ischemic stroke, have approximately the same relative risk of death from cardiovascular causes as patients with a history of coronary or cerebrovascular disease. Despite the high prevalence of PAD and the strong association with cardiovascular morbidity and mortality, patients with PAD are less likely to receive appropriate treatment for their atherosclerotic risk factors than those who are being treated for coronary artery disease. Atherosclerotic risk factor identification and modification play an important role in reducing the number of adverse outcomes among patients with atherosclerosis. Risk reduction therapy decreases the risk of cardiovascular mortality and morbidity in patients with PAD. In this study, we aim to evaluate the effectiveness of a lifestyle and risk factor modification intervention programme in achieving treatment goals for PAD risk factors. METHODS: This is a randomised, parallel group, active-control trial to compare the effectiveness of the risk factor modification intervention programme to standard healthcare in a tertiary vascular care centre, in the reduction of modified risk factors in PAD patients. The primary outcome of this study is to evaluate the effectiveness of a lifestyle and risk factor modification intervention programme in achieving treatment goals for PAD risk factors at 3 and 12 months. The secondary outcomes are to compare the impact of the programme on clinical outcomes in PAD patients at 12 months. Secondary outcomes include amputation-free survival, clinical improvement, haemodynamic improvement, need for revascularisation procedures, outcomes of revascularisation procedures, changes in quality of life and the incidence of adverse events. DISCUSSION: This study will provide clear evidence on the effectiveness of a lifestyle and risk factor modification intervention programme in achieving treatment goals for PAD risk factors, through a high-quality, well-powered clinical trial. TRIAL REGISTRATION: This trial was registered (11/07/2017) on the European Clinical Trials Database (EudraCT number 2017-002964-41) and ClinicalTrials.gov ( NCT03935776 ) which was registered on 02 May 2019.

Defining enhanced recovery after resection of peri-hilar cholangiocarcinoma.

INTRODUCTION: Enhanced recovery after surgery (ERAS) for peri-hilar cholangiocarcinoma (pCCA) has not been described in the literature. This study examined patients undergoing pCCA resection within a standard post hepatectomy ERAS pathway to define achievable targets suitable for these patients. METHODS: Patients undergoing pCCA resection at University Hospital Aintree (January 2009-October 2017) were identified. Achievement of key ERAS outcomes was assessed. Patients were stratified on incidence of major complications and pre-operative cardiopulmonary exercise testing. Chi Square and Mann Whitney analyses were undertaken as appropriate. Achievable ERAS targets were derived from patients who did not develop a major complication. RESULTS: 46 patients underwent resection with enhanced recovery. Median age 65 (24 male: 22 female). Key ERAS outcomes in patients who did not experience major complications are described as medians (interquartile range): length of stay 8 days (6-13), duration critical care 2 days (2-4), inotropes 6 h (0-24), epidural 3 days (3-4), early mobilization day 1 (1-2), full mobilization day 3 (3-4), urinary catheter removal day 4 (3-5), NGT removal day 1 (1-2) and restoration oral nutrition day 2 (2-4). Patients deemed high risk pre-operatively or those who developed major complications post-operatively required significantly longer critical care (p = 0.008 and p = 0.002 respectively). Other ERAS targets remained achievable in similar timeframes. CONCLUSIONS: ERAS for pCCA is achievable. Applicable ERAS standards are defined which take into account minor complications. High risk patients and those with major complications can be appropriately managed in an ERAS pathway, though there is increased need for critical care support.

Adherence to early mobilisation: Key for successful enhanced recovery after liver resection.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) has been proven effective in liver surgery. Adherence to the ERAS pathway is variable. This study seeks to evaluate adherence to key components of an ERAS protocol in liver resection, and identify the components associated with successful clinical outcomes. METHOD: All patients undergoing liver resections for two consecutive years were included in our ERAS pathway. Six key components of ERAS included preoperative assessment, nutrition and gastrointestinal function, postoperative analgesia, mobilisation and discharges. Successful accomplishment of ERAS was defined as hospital discharge by postop day (POD) 6. Adherences of these elements were compared between the successful and un-successful groups. RESULTS: During the studied period, 223 patients underwent liver resections, among which 103 had major hepatectomies. N = 147 patients (66%) were discharged within our ERAS protocol target (6 days). On multivariable analysis, sitting out of bed by POD 1 (p < 0.03), walking by POD 3 (p = 0.03), removal of urinary catheter by POD 3 (p < 0.01), and avoiding major complications (p < 0.01) were factors associated with successful completion to our ERAS protocol; whereas advanced age (p = 0.34) and discontinuation of PCA/epidural by POD 3 (p = 0.50) were not significant parameters. There was a significant difference in the length of stay (p < 0.01) following major and minor liver resection, of which the indications for surgery also varied significantly. There was no difference in hospital re-admission rate, and morbidity and mortality between major and minor liver resection. CONCLUSIONS: Facilitating early mobilisation and reducing postoperative complications are keys to successful outcomes of ERAS in liver resection.

Human eosinophils modulate peripheral blood mononuclear cell response to Schistosoma mansoni adult worm antigen in vitro.

High numbers of eosinophils are observed in parasitic infections and allergic diseases, where they are proposed to be terminally differentiated effector cells that play beneficial role in host defence, or cause harmful inflammatory response. Eosinophils have been associated with killing of schistosomulae in vitro, but there is growing evidence that eosinophils can play additional immuno-regulatory role. Here, we report results of a study that examines peripheral blood mononuclear cell (PBMC) cytokine responses to Schistosoma mansoni adult worm antigen (SWA) when stimulated alone or enriched with autologous eosinophils. Production of the Th-2 type cytokines interleukin (IL)-4, IL-5 and IL-13 was lower (P = 0·017, 0·018 and <0·001, respectively) in PBMC + eosinophil cultures than in PBMC-only cultures stimulated with SWA. Substantial levels of IL-13, IL-10, interferon gamma and tumour necrosis factor alpha were recorded in cultures of eosinophils, but none of these cytokines showed significant association with the observed eosinophil-induced drop in cytokine responses of PBMC. Transwell experiments suggested that the observed effect is due to soluble mediators that downmodulate production of Th-2 type cytokines. This study shows that eosinophils may down-modulate schistosome-specific Th-2 type cytokine responses in S. mansoni-infected individuals. The mechanism of this immune modulation remains to be elucidated.

Randomized clinical trial of prehabilitation before planned liver resection.

BACKGROUND: Patients with low fitness as assessed by cardiopulmonary exercise testing (CPET) have higher mortality and morbidity after surgery. Preoperative exercise intervention, or prehabilitation, has been suggested as a method to improve CPET values and outcomes. This trial sought to assess the capacity of a 4-week supervised exercise programme to improve fitness before liver resection for colorectal liver metastasis. METHODS: This was a randomized clinical trial assessing the effect of a 4-week (12 sessions) high-intensity cycle, interval training programme in patients undergoing elective liver resection for colorectal liver metastases. The primary endpoint was oxygen uptake at the anaerobic threshold. Secondary endpoints included other CPET values and preoperative quality of life (QoL) assessed using the SF-36®. RESULTS: Thirty-eight patients were randomized (20 to prehabilitation, 18 to standard care), and 35 (25 men and 10 women) completed both preoperative assessments and were analysed. The median age was 62 (i.q.r. 54-69) years, and there were no differences in baseline characteristics between the two groups. Prehabilitation led to improvements in preoperative oxygen uptake at anaerobic threshold (+1·5 (95 per cent c.i. 0·2 to 2·9) ml per kg per min) and peak exercise (+2·0 (0·0 to 4·0) ml per kg per min). The oxygen pulse (oxygen uptake per heart beat) at the anaerobic threshold improved (+0·9 (0·0 to 1·8) ml/beat), and a higher peak work rate (+13 (4 to 22) W) was achieved. This was associated with improved preoperative QoL, with the overall SF-36® score increasing by 11 (95 per cent c.i. 1 to 21) (P = 0·028) and the overall SF-36® mental health score by 11 (1 to 22) (P = 0·037). CONCLUSION: A 4-week prehabilitation programme can deliver improvements in CPET scores and QoL before liver resection. This may impact on perioperative outcome. REGISTRATION NUMBER: NCT01523353 (https://clinicaltrials.gov).

Blood cultures in acute surgical admissions.

INTRODUCTION: Obtaining blood cultures prior to the administration of antimicrobial therapy was a key recommendation of the 2012 UK Surviving Sepsis Campaign. Few studies have examined the effect blood cultures have on clinical management and there have been none on acute surgical admissions. This retrospective study sought to evaluate the effect of blood cultures on clinical management in acute surgical admissions. METHODS: Data on acute surgical patients admitted between 1 January and 31 December 2012 were extracted from hospital records. Patients given intravenous antibiotics within 24 hours of admission were identified. Data collected included antibiotics administered, blood culture results, admission observations and white blood cell count. Case notes were reviewed for patients with positive cultures to establish whether the result led to a change in management. RESULTS: Of 5,887 acute surgical admissions, 1,346 received intravenous antibiotics within 24 hours and 978 sets of blood cultures were taken in 690 patients. The recommended two sets of cultures were obtained in 246 patients (18%). Patients who had blood cultures taken had the same in-hospital mortality as those who had none taken (3.6% vs 3.5%, p=0.97). Blood cultures were positive in 80 cases (11.6%). The presence of systemic inflammatory response syndrome did not increase positivity rates (12.9% vs 10.3%, p=0.28). Overall, cultures altered management in two patients (0.3%). CONCLUSIONS: Blood cultures rarely affect clinical management. In order to assess the additional value that blood cultures bring to sepsis management in acute surgical admissions, a prospective randomised trial focusing on outcome is needed.

A systematic review of the role of hepatectomy in the management of metastatic renal cell carcinoma.

AIM: This review sought to systematically appraise the literature to establish the role of hepatectomy in treating renal cell carcinoma hepatic metastases. METHOD: Medline and EMBASE were systematically searched for papers reporting survival of patients who underwent hepatectomy for metastatic renal cell carcinoma. RESULTS: Six studies containing 140 patients were included. There were no randomised controlled trials. Perioperative mortality was 4.3%, with reported morbidity between 13 and 30%. Patients with metachronous presentation, and a greater time interval between resection of primary tumour and development of metachronous metastases, appeared to have better survival. There was no difference in survival between patients with solitary and multiple metastases. CONCLUSION: Few patients with hepatic metastases from renal cell carcinoma are suitable for hepatectomy as metastatic disease is usually widespread. Selected patients may experience a survival benefit, but identifying these patients remains difficult.

Controversies in the oncosurgical management of liver limited stage IV colorectal cancer.

Colorectal cancer is the fourth most common cancer diagnosis in the world (around 1.2 million diagnoses each year), and accounts for the second highest number of deaths. Over half of patients with colorectal cancer will develop liver metastases, with one quarter presenting in stage IV. There is growing evidence that patients with liver-limited disease represent a distinct biological cohort who will benefit from aggressive management. Only a minority of patients are technically resectable, but around 40% of patients with resected liver limited disease are alive 5 years after diagnosis compared with less than 1% for those with disseminated disease. Novel surgical techniques have been developed to allow more patients to undergo resection and there is also growing recognition that the chemotherapeutic manipulation of irresectable disease may bring some patients to resection with good long-term outcome. Perioperative chemotherapy can also improve long-term outcome through improved biological selection and destruction of occult micrometastases. This review outlines current oncosurgical treatment strategies for liver-limited stage IV colorectal cancer, and discusses some of the controversies surround the management of these complex patients.

Radiological assessment of response to neoadjuvant transcatheter hepatic therapy with irinotecan-eluting beads (DEBIRI(®)) for colorectal liver metastases does not predict tumour destruction or long-term outcome.

INTRODUCTION: Transcatheter hepatic therapy with irinotecan-eluting beads (DEBIRI(®)) allows targeted delivery of irinotecan direct to liver tissue and colorectal liver metastases (CRLM). Accurate assessment of tumour response to therapy is vital to guide optimal treatment. Preliminary work has suggested existing criteria for radiological response may not reflect pathological response after neoadjuvant DEBIRI. This study assessed the relationship between existing and novel radiological response criteria and pathological tumour response as well as long-term outcome. METHODS: Patients with easily resectable CRLM were treated with DEBIRI 4 weeks prior to resection and pathological tumour response graded using a validated system. Radiological response was assessed using RECIST and novel morphological response criteria. RESULTS: Twenty-two patients with 37 lesions were treated with DEBIRI. Median residual tumour was 20% (range 0-80), median necrosis 45% (10-100) and median fibrosis 10% (10-70). Twenty patients (91%) demonstrated stable disease by RECIST, with 11 (50%) demonstrating partial morphological response. Neither radiological response criteria correlated with pathological response. Overall median disease free survival (DFS) was 13.6 months (95% CI 4.7-22.5). Radiological response was not associated with DFS. CONCLUSION: Existing criteria reporting short-term radiological response to DEBIRI do not accurately predict pathological tumour response or long-term outcome. Further work is necessary to define the optimum timing and method of assessing response to DEBIRI.

Routine staging laparoscopy has no place in the management of colorectal liver metastases.

AIMS: Staging laparoscopy has been recommended in the management of patients with colorectal liver metastases prior to hepatectomy in order to reduce the incidence and associated morbidity of futile laparotomies. The utility of staging laparoscopy has not been assessed in patients undergoing CT, PET-CT and MRI as standard preoperative staging. METHODS: All patients undergoing attempted open hepatectomy for colorectal liver metastases between 1/4/2008 and 31/3/2012 were identified from a prospectively maintained research database. All patients who underwent futile laparotomy were identified, with demographics and operative notes subsequently analysed. RESULTS: A total of 274 patients underwent attempted open hepatectomy during the study period. At laparotomy 12 (4.4%) patients were found to have irresectable disease. There were no unifying demographic factors within the patients undergoing futile laparotomy. CONCLUSIONS: With modern imaging, the potential yield of staging laparoscopy is low. Staging laparoscopy should not be used routinely, but may have a role in the case of specific clinical concerns.

A late IL-33 response after exposure to Schistosoma haematobium antigen is associated with an up-regulation of IL-13 in human eosinophils.

IL-33, a proposed alarmin, stimulates innate immune cells and Th2 cells to produce IL-13 and is rapidly upregulated upon antigen exposure in murine helminth infection. The human IL-33 response to helminth antigen was analysed in Malians infected with Schistosoma haematobium by disrupting parasite integrity via chemotherapy. Plasma IL-33 was measured pretreatment, and 24 h and 9 weeks post-treatment. At 24 h post-treatment, IL-33 levels were low. Nine week post-treatment IL-33 levels were elevated and were associated with an increase in intracellular IL-13 in eosinophils. Up-regulation of intracellular IL-13 in eosinophils was also associated with eosinophil expression of ST2L, the IL-33 receptor. IL-33 may play an important downstream role in the human response to schistosome adult worm antigen exposure.

Systematic review and meta-analysis of follow-up after hepatectomy for colorectal liver metastases.

BACKGROUND: The evidence surrounding optimal follow-up after liver resection for colorectal metastases remains unclear. A significant proportion of recurrences occur in the early postoperative period, and some groups advocate more intensive review at this time. METHODS: A systematic review of literature published between January 2003 and May 2010 was performed. Studies that described potentially curative primary resection of colorectal liver metastases that involved a defined follow-up protocol and long-term survival data were included. For meta-analysis, studies were grouped into intensive (more frequent review in the first 5 years after resection) and uniform (same throughout) follow-up. RESULTS: Thirty-five studies were identified that met the inclusion criteria, involving 7330 patients. Only five specifically addressed follow-up. Patients undergoing intensive early follow-up had a median survival of 39·8 (95 per cent confidence interval 34·3 to 45·3) months with a 5-year overall survival rate of 41·9 (34·4 to 49·4) per cent. Patients undergoing routine follow-up had a median survival of 40·2 (33·4 to 47·0) months, with a 5-year overall survival rate of 38·4 (32·6 to 44·3) months. CONCLUSION: Evidence regarding follow-up after liver resection is poor. Meta-analysis failed to identify a survival advantage for intensive early follow-up.

Molecular characterisation of kappa-5, a major antigenic glycoprotein from Schistosoma mansoni eggs.

The major immunopathological consequences of infection with Schistosoma mansoni, a T helper type 2 response and granuloma formation leading to fibrotic tissue damage, are caused by the egg stage of the parasite. Three antigens of S. mansoni eggs, termed IPSE/alpha-1, omega-1 and kappa-5, have been found to be the primary targets of the egg-directed antibody response of the host. Here, we report on the isolation, cloning and characterisation of kappa-5. Apart from an uncharacterised mRNA sequence in S. japonicum, no significant similarities of kappa-5 to known sequences from other species were found. In contrast to IPSE/alpha-1 and omega-1, which have been found only in eggs, kappa-5 was present in miracidia as well as in eggs at the mRNA and protein levels. In eggs, isoforms of kappa-5 were observed with both three and four fully occupied N-glycosylation sites, while in miracidia only one isoform with four N-glycans could be detected. Interestingly, in Western blots sera from S. mansoni-infected Africans were reactive against kappa-5 with IgE and IgG isotype antibodies, but against IPSE/alpha-1 and omega-1 only with IgG antibodies. The further characterisation of kappa-5 as one of the three major egg antigens should help to better understand the immunology and immunopathology of schistosomiasis.

How far does screening women for domestic (partner) violence in different health-care settings meet criteria for a screening programme? Systematic reviews of nine UK National Screening Committee criteria.

OBJECTIVES: The two objectives were: (1) to identify, appraise and synthesise research that is relevant to selected UK National Screening Committee (NSC) criteria for a screening programme in relation to partner violence; and (2) to judge whether current evidence fulfils selected NSC criteria for the implementation of screening for partner violence in health-care settings. DATA SOURCES: Fourteen electronic databases from their respective start dates to 31 December 2006. REVIEW METHODS: The review examined seven questions linked to key NSC criteria: QI: What is the prevalence of partner violence against women and what are its health consequences? QII: Are screening tools valid and reliable? QIII: Is screening for partner violence acceptable to women? QIV: Are interventions effective once partner violence is disclosed in a health-care setting? QV: Can mortality or morbidity be reduced following screening? QVI: Is a partner violence screening programme acceptable to health professionals and the public? QVII: Is screening for partner violence cost-effective? Data were selected using different inclusion/exclusion criteria for the seven review questions. The quality of the primary studies was assessed using published appraisal tools. We grouped the findings of the surveys, diagnostic accuracy and intervention studies, and qualitatively analysed differences between outcomes in relation to study quality, setting, populations and, where applicable, the nature of the intervention. We systematically considered each of the selected NSC criteria against the review evidence. RESULTS: The lifetime prevalence of partner violence against women in the general UK population ranged from 13% to 31%, and in clinical populations it was 13-35%. The 1-year prevalence ranged from 4.2% to 6% in the general population. This showed that partner violence against women is a major public health problem and potentially appropriate for screening and intervention. The HITS (Hurts, Insults, Threatens and Screams) scale was the best of several short screening tools for use in health-care settings. Most women patients considered screening acceptable (range 35-99%), although they identified potential harms. The evidence for effectiveness of advocacy is growing, and psychological interventions may be effective, but not necessarily for women identified through screening. No trials of screening programmes measured morbidity and mortality. The acceptability of partner violence screening among health-care professionals ranged from 15% to 95%, and the NSC criterion was not met. There were no cost-effectiveness studies, but a Markov model of a pilot intervention to increase identification of survivors of partner violence in general practice found that such an intervention was potentially cost-effective. CONCLUSIONS: Currently there is insufficient evidence to implement a screening programme for partner violence against women either in health services generally or in specific clinical settings. Recommendations for further research include: trials of system-level interventions and of psychological and advocacy interventions; trials to test theoretically explicit interventions to help understand what works for whom, when and in what contexts; qualitative studies exploring what women want from interventions; cohort studies measuring risk factors, resilience factors and the lifetime trajectory of partner violence; and longitudinal studies measuring the long-term prognosis for survivors of partner violence.

Hepatosplenomegaly associated with chronic malaria exposure: evidence for a pro-inflammatory mechanism exacerbated by schistosomiasis.

In sub-Saharan Africa, chronic hepatosplenomegaly, with palpable firm/hard organ consistency, is common, particularly among school-aged children. This morbidity can be caused by long-term exposure to malaria, or by Schistosoma mansoni, and it is exacerbated when these two occur together. Although immunological mechanisms probably underlie the pathogenic process, these mechanisms have not been identified, nor is it known whether the two parasites augment the same mechanisms or induce unrelated processes that nonetheless have additive or synergistic effects. Kenyan primary schoolchildren, living in a malaria/schistosomiasis co-transmission area, participated in cross-sectional parasitological and clinical studies in which circulating immune modulator levels were also measured. Plasma IL-12p70, sTNF-RII, IL-10 and IL-13 levels correlated with relative exposure to malaria, and with hepatosplenomegaly. Soluble-TNF-RII and IL-10 were higher in children infected with S. mansoni. Hepatosplenomegaly caused by chronic exposure to malaria was clearly associated with increased circulating levels of pro-inflammatory mediators, with higher levels of regulatory modulators, and with tissue repair cytokines, perhaps being required to control the inflammatory response. The higher levels of regulatory modulators amongst S. mansoni infected children, compared to those without detectable S. mansoni and malarial infections, but exposed to malaria, suggest that S. mansoni infection may augment the underlying inflammatory reaction.

Intestinal polyparasitism in a rural Kenyan community.

BACKGROUND: Polyparasitism seems to be a common feature in human populations in sub-Saharan Africa. However, very little is known about its epidemiological significance, its long term impact on human health or the types of interactions that occur between the different parasite species involved. OBJECTIVES: To determine the prevalence and co-occurrence of intestinal parasites in a rural community in the Kibwezi, Makueni district, Kenya. DESIGN: A cross sectional study. SETTING: Kiteng'ei village, Kibwezi, Makueni district, between May and September 2006. SUBJECTS: One thousand and forty five who comprised of 263 adult males, 271 adult females > 15 years of age and 232 boys, and 279 girls <15 years of age. INTERVENTIONS: All infected members of the community were offered Praziquantel (at dosages of 40 mg/kg body weight) for Schistosomiasis and Albendazole (600 mg) for soil transmitted helminths. RESULTS: A total of ten intestinal parasite species (five protozoan and five helminth parasite species) were present in this community and polyparasitsm was common in individuals 5-24 years of age with no gendar related differences. Most of the infections were mild. The protozoan parasites of public health significance present were Entamoeba histolytica and Giardia lamblia with prevalence of 12.6% and 4.2%, respectively. The helminth parasites of public health significance in the locality were Schistosoma mansoni with a prevalence of 28%, and hookworms prevalence of 10%. About 53% of the study population harboured intestinal parasite infections, with 31% of the infected population carrying single parasite species infections, and 22% harbouring two or more intestinal parasite species per individual. Significant positive associations (p values <0.05) were observed between S. mansoni and hookworms, hookworms and Hymenolepis. nana and Entamoeba histolytica and Entamoeba coli. CONCLUSION: Intestinal polyparasitism was common in the Kiteng'ei community, particularly in individuals aged of 5-24 years old. An integrated control programme of approach would be recommended for the control of S. mansoni, hookworms and Entamoeba histolytica for this community.

Parasitic worms and inflammatory diseases.

The debate on whether infection precipitates or prevents autoimmunity remains a contentious one. Recently the suggestion that some unknown microbe can be at the origin of some chronic inflammatory diseases has been countered by accumulating evidence that decreasing infection rates might have an important role to play in the rising prevalence of autoimmune disorders. The 'Hygiene Hypothesis' was initially postulated to explain the inverse correlation between the incidence of infections and the rise of allergic diseases, particularly in the developed world. Latterly, the Hygiene Hypothesis has been extended to also incorporate autoimmune diseases in general. Amongst the various infectious agents, a particular emphasis has been put on the interaction between parasitic worms and humans. Worm parasites have co-evolved with the mammalian immune system for many millions of years and during this time, they have developed extremely effective strategies to modulate and evade host defences and so maintain their evolutionary fitness. It is therefore reasonable to conclude that the human immune system has been shaped by its relationship with parasitic worms and this may be a necessary requirement for maintaining our immunological health. Fully understanding this relationship may lead to novel and effective treatments for a host of deleterious inflammatory reactions.

Characterization of immunoglobulin binding by schistosomes.

Although controversial, schistosomes are believed to cloak themselves in antibody through non-specific interactions with the immunoglobulin (Ig) molecule. The acquisition of host Ig by the schistosome may mask its foreign status and/or interfere with Fc-dependent functions. We report experiments aimed at characterizing the interaction between Ig-Fc and paramyosin, a schistosome Fc-receptor previously reported to bind human IgG. We show that certain Ig classes, in particular murine IgG2b and IgG3, are not only able to bind recombinant paramyosin, but also associate with other parasite proteins. The Fc region of IgG contains four hydrophobic patches, two of which are known to interact with distinct molecules: one in the Cgamma2-Cgamma3 interdomain region bound by protein G, mannose binding lectin (MBL), and the neonatal Fc-receptor (FcRn), and one at the top of the Cgamma2 domain bound by phagocytic FcgammaRs and C1q. We provisionally discounted the involvement of these regions, since IgG binding by paramyosin did not inhibit FcgammaR-mediated NADPH respiratory bursts, and protein G was unable to block IgG binding to paramyosin. Given their apparent low affinity, we postulate hydrogen bonding between reactive residues in a hydrophobic patch at the bottom of the Cgamma3 domain and negatively charged Glu or Asp amino acids in paramyosin.

Comparative epidemiology of Chlamydia trachomatis infection among men attending sexually transmitted disease clinics with and without indication for testing.

Understanding the epidemiology of Chlamydia trachomatis infection in men without indication for testing (without symptoms, signs, or a report of sexual contact with an infected partner) is of crucial importance to reduce the heavy burden of this infection, particularly because this group of men is not usually offered testing in different clinical settings. Using electronic medical records of two STD clinics in Connecticut, 2000-02, this study identified the risk factors of C. trachomatis infection in men with and without indication for testing. In both groups, men who were younger than 30, African-American, or had a prior history of C. trachomatis infection were significantly more likely to be infected. Since a system for routine reproductive health care of young men does not currently exist, health-care providers need to promote an increased awareness of C. trachomatis infection among their male patients who are at increased risk of infection.