Targeting C-reactive protein for the treatment of cardiovascular disease.

Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments.

The use of the Framingham equation to predict myocardial infarctions in HIV-infected patients: comparison with observed events in the D:A:D Study.

Background: The D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs) Study, a prospective observational study on a cohort of 23 468 patients with HIV infection, indicated that the incidence of myocardial infarction (MI) increased by 26% per year of exposure to combination antiretroviral treatment (CART). However, it remains unclear whether the observed increase in the rate of MI in this population can be attributed to changes in conventional cardiovascular risk factors.

Objective: To compare the number of MIs observed among participants in the D:A:D Study with the number predicted by assuming that conventional cardiovascular risk equations apply to patients with HIV infection.

Human serum amyloid P component protects against Escherichia coli O157:H7 Shiga toxin 2 in vivo: therapeutic implications for hemolytic-uremic syndrome.

Shiga toxin (Stx) 2 causes hemolytic-uremic syndrome (HUS), an intractable and often fatal complication of enterohemorrhagic Escherichia coli O157:H7 infection. Here, we show that serum amyloid P component (SAP), a normal human plasma protein, specifically protects mice against the lethal toxicity of Stx2, both when injected into wild-type mice and when expressed transgenically; in the presence of human SAP, there was greatly reduced in vivo localization of Stx2 to the kidneys, suggesting a possible mechanism of protection. In humans, circulating SAP concentrations did not differ between patients with suspected enterohemorrhagic E.

Effective therapy has altered the spectrum of cause-specific mortality following HIV seroconversion.

Introduction: Although HAART has led to a reduction in overall mortality among HIV-infected individuals, its impact on death from specific causes is unknown.

Methods: Twenty-two cohorts of HIV-infected individuals with known dates of seroconversion are pooled in the CASCADE collaboration. Causes of death (COD) were categorized into three AIDS-related and seven non-AIDS-related causes.

Providing written information on HIV testing improves patient knowledge but does not affect test uptake.

The objective of this study is to determine the effect of providing written information about HIV testing on patient knowledge and test uptake. Patients attending our genitourinary medicine clinic in July 2003 were offered written information about HIV and the test. They were asked to complete a questionnaire which elicited knowledge provided on the leaflet.

Binding of different monosaccharides by lectin PA-IIL from Pseudomonas aeruginosa: thermodynamics data correlated with X-ray structures.

The lectin from Pseudomonas aeruginosa (PA-IIL) is involved in host recognition and biofilm formation. Lectin not only displays an unusually high affinity for fucose but also binds to L-fucose, L-galactose and D-arabinose that differ only by the group at position 5 of the sugar ring. Isothermal calorimetry experiments provided precise determination of affinity for the three methyl-glycosides and revealed a large enthalpy contribution.

Herpes simplex virus type 2 (HSV-2) seroprevalence at the time of HIV-1 diagnosis and seroincidence after HIV-1 diagnosis in an ethnically diverse cohort of HIV-1-infected persons.

Objective: The objective of this study was to determine herpes simplex virus type 2 (HSV-2) seroprevalence at HIV-1 diagnosis and seroincidence > or =1 year after HIV-1 diagnosis.

Methods: HSV type-specific antibodies were detected by enzyme immunoassay.

Results: The cohort comprised 850 adults diagnosed HIV-positive in 1986-2001 and followed for a median of 3 years.

3-month and 12-month mortality after first liver transplant in adults in Europe: predictive models for outcome.

Background: Mortality after liver transplantation depends on heterogeneous recipient and donor factors. Our aim was to assess risk of death and to develop models to help predict mortality after liver transplantation.

Methods: We analysed data from 34,664 first adult liver transplants from the European Liver Transplant Registry to identify factors associated with mortality at 3-months (n=21,605 in training dataset) and 12-months (n=18,852 in training dataset) after transplantation.

Deaths in the era of HAART: contribution of late presentation, treatment exposure, resistance and abnormal laboratory markers.

Objectives: To describe the characteristics of deaths that occur among HIV-positive individuals in the HAART era.

Design: Observational database.

Methods: Deaths were reviewed that occurred among HIV-positive individuals seen at the Royal Free Hospital, London between January 1998 and December 2003.

Predictors of hypertension and changes of blood pressure in HIV-infected patients.

Objective: We assessed predictors of changes in systolic (SBP) and diastolic (DBP) blood pressure during follow-up and of the development of hypertension in HIV-infected individuals.

Methods: International cohort collaborative study (D:A:D) of established prospective cohorts of HIV-1-infected patients. Longitudinal analysis of changes in blood pressure (BP) was performed using mixed effects models in 17170 patients.

Cervical screening in HIV-positive women: characteristics of those who default and attitudes towards screening.

Objectives: To determine the characteristics of HIV-positive women who undergo cervical screening and to identify negative attitudes and experiences of these women to screening and the factors associated with these.

Methods: We compared the Royal Free Cohort data from 59 newly diagnosed HIV-infected women, 31 of whom did and 28 of whom did not attend for cervical screening in 2001, and from 227 women under active cervical screening follow-up (at least one cervical screen since June 2001) and 88 HIV-infected women lost to follow-up (not screened since January 2001). Attitudes to screening were investigated with the aid of a questionnaire given to all women attending clinic who had had a previous colposcopy.

Effects of highly active antiretroviral therapy on paediatric metabolite levels.

Objectives: Highly active antiretroviral therapy (HAART) has extended survival of HIV-infected children into adulthood, raising concerns about long-term metabolic changes in childhood.

Methods: A longitudinal study of metabolite levels in paediatric HIV-infected patients before and after starting HAART (January 2000 to June 2003). The effects of HAART on nonfasting blood levels of total (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol, cholesterol ratio and lactate were analysed using mixed-effects regression.

Determinants of response to first HAART regimen in antiretroviral-naïve patients with an estimated time since HIV seroconversion.

Objective: To study the determinants of immunological and virological response to highly active antiretroviral therapy (HAART) in naïve patients, adjusting for time since HIV-1 seroconversion.

Design: Data from HIV-cohort studies where dates of seroconversion have been reliably estimated. Methods In previously untreated patients, short- and long-term marker responses from HAART initiation (three or more antiretroviral drugs) to the end of follow-up or any treatment modification were considered using mixed effects models accounting for undetectable HIV viral load and informative dropout.

Time trends in primary resistance to HIV drugs in the United Kingdom: multicentre observational study.

Objective: To examine whether the level of primary resistance to HIV drugs is increasing in the United Kingdom.

Design: Multicentre observational study.

Setting: All virology laboratories in the United Kingdom carrying out tests for HIV resistance as part of routine clinical care.

Incidence of Tuberculosis among HIV-infected patients receiving highly active antiretroviral therapy in Europe and North America.

Background: We obtained estimates of the incidence of tuberculosis (TB) among patients receiving HAART and identified determinants of the incidence.

Methods: We analyzed the incidence of TB during the first 3 years after initiation of HAART among 17,142 treatment-naive, AIDS-free persons starting HAART who were enrolled in 12 cohorts from Europe and North America. We used univariable and multivariable Poisson regression models to identify factors associated with the incidence.

Proinflammatory effects of bacterial recombinant human C-reactive protein are caused by contamination with bacterial products, not by C-reactive protein itself.

Intravenous administration to human volunteers of a commercial preparation of recombinant human C-reactive protein (CRP) produced in Escherichia coli was recently reported in this journal to induce an acute phase response of serum amyloid A protein (SAA) and of CRP itself, and to activate the coagulation system. The authors concluded that CRP is probably a mediator of atherothrombotic disease. Here we confirm that this recombinant CRP preparation was proinflammatory both for mouse macrophages in vitro and for mice in vivo, but show that pure natural human CRP had no such activity.

Prevalence of hepatitis C-related cirrhosis in elderly Asian patients infected in childhood.

Background & Aims: Approximately 20% of hepatitis C virus (HCV) patients develop cirrhosis from infection after about 20 years. The proportion of patients developing cirrhosis for longer than 30 years after infection is unknown. Our objectives were to determine the prevalence of HCV-related cirrhosis in a population of Asian patients who were infected in childhood 20 to 80 years ago and compare this with the prevalence of cirrhosis in Caucasian patients referred to the same hospitals.

The attitude of patients towards medical students in a sexual health clinic.

Objectives: To determine patient attitudes toward medical students in the sexual health clinic, and to describe factors associated with patient refusal of medical student involvement.

Method: A self administered questionnaire was given to 259 consecutive patients attending the general genitourinary medicine clinic. Participants were asked to indicate their attitude to questioning and/or examination by medical students.

Effect of treatment interruption monitored by CD4 cell count on mitochondrial DNA content in HIV-infected patients: a prospective study.

Background: HIV infection per se and HAART can alter mitochondrial functionality, leading to a decrease in mitochondrial DNA content.

Objective: To evaluate whether treatment interruption monitored by CD4 cell count can restore mitochondrial DNA content in peripheral blood lymphocytes.

Methods: Mitochondrial DNA content was measured in platelet-free CD4 and CD8 T cells by real-time polymerase chain reaction; flow cytometry was used to identify and quantify activated CD4 and CD8 T lymphocytes.

The rate of viral rebound after attainment of an HIV load <50 copies/mL according to specific antiretroviral drugs in use: results from a multicenter cohort study.

Background: Relatively few data are available on the association between the use of specific antiretroviral drugs and the rate of viral rebound in those attaining a viral load (VL) <50 copies/mL while receiving highly active antiretroviral therapy (HAART).

Methods: Patients achieving a VL <50 copies/mL for the first time while receiving HAART were followed until viral rebound (2 consecutive VLs >500 copies/mL). Pre-HAART antiretroviral-naive patients were analyzed separately from those with nucleoside reverse transcriptase inhibitor (NRTI) experience.

Estimating HIV-1 drug resistance in antiretroviral-treated individuals in the United Kingdom.

Good estimates of the prevalence of human immunodeficiency virus drug resistance are important for assessing requirements for new drug classes and modeling the spread of resistance. However, little consensus exists on optimal methodologies to generate such data. To compare methodologies, we used the national data set of resistance tests from >4000 patients in the United Kingdom performed between 1998 and 2002.

The epidemiology of genital infection with herpes simplex virus types 1 and 2 in genitourinary medicine attendees in inner London.

Objective: To characterise the epidemiological and clinical features of genital herpes and the diagnostic role of HSV-2 specific serology in an ethnically diverse cohort of genitourinary medicine (GUM) attendees in inner London.

Methods: Genital swabs (n = 186) were tested by real time polymerase chain reaction (PCR) and serum samples (n = 70) by HSV-2 specific enzyme linked immunoassay (ELISA).

Results: Among 186 patients (median age 29 years), 104/186 (56%) were male and 176/186 (95%) heterosexual; ethnicity was predominantly black Caribbean (76/186, 41%), white (65/186, 35%), or black-African (41/186, 22%).

Insulin resistance plays a significant role in liver fibrosis in chronic hepatitis C and in the response to antiviral therapy.

Objectives: To assess whether insulin resistance is associated with liver fibrosis in a group of patients with chronic hepatitis C virus (HCV) infection and whether there were any differences in insulin resistance between Asians and the indigenous Caucasian population. Secondly, to assess whether insulin resistance is associated with sustained virological response to antiviral therapy.

Methods: We determined insulin resistance in 59 (30 Caucasians; 29 Asians) consecutive patients with HCV prior to starting antiviral therapy.