Vascular complications of Q-fever infections.

INTRODUCTION: Coxiella burnetii is a strict intracellular pathogen causing Q fever, a worldwide zoonosis with an extensive animal reservoir. Chronic Q fever infections are frequently associated with cardiovascular complications, mainly endocarditis, and also aortic aneurysms and vascular-graft infection. We present four cases of chronic Q fever infections and associated vascular complications, and review the literature to identify major symptoms and assess the prevalence, treatment and outcome in these challenging patients. MATERIALS AND METHODS: The demographic and clinical data of four patients presenting at our unit were analysed. PubMed was searched to identify articles describing patients with chronic Q-fever-associated vascular complications. RESULTS: Combining our own with the published experience, 58 cases (49 male) of chronic Q-fever-associated vascular complications were identified. The average age of the patients was 64 years (range: 30-83 years). As many as 26 patients had vascular graft infections (25 Dacron/polytetrafluoroethylene (PTFE), one homograft) and 32 had infected aneurysms. The majority of these patients presented with fever (n = 40) and/or pain (n = 43). Weight loss and fatigue were seen in 25 and 14 patients, respectively. Aneurysm rupture, aorto-enteric fistulae and lower-limb embolisation were seen in nine, four and four patients, respectively. Concurrent endocarditis was seen in two patients, whereas, for 15 cases, this information was not available. Patients were treated with antibiotics for an average of 23 months (range 1-54 months). Treatment of infected vascular segments was described in 50 patients. Ten patients were treated conservatively whilst 40 underwent resection of the infected vessel and reconstruction with a graft. Major surgical complications (graft infection, n = 3;aorto-enteric fistula, n = 2; bleeding, n = 1; anastomotic leakage, n = 1; aortic dissection, n = 1; vertebral osteomyelitis, n = 3; graft thrombosis, n = 1; renal failure, n = 2; and pneumonia, n = 1) were reported in 11 cases (21%) and were not specified in 13. The overall mortality was 24% (14/58). Seven (18%) surgically treated patients died. Six of them died within 6 months of surgery and one patient at 3 years' follow-up. Seven out of 10 of the conservatively treated patients died within 3 years of diagnosis. CONCLUSION: Aneurysms associated with Q-fever infections tend to be complicated, requiring challenging surgical corrections, and long-term antibiotic treatment. Major complications and mortality rates are significant, especially in conservatively treated patients.

Spatio-temporal curvature pattern of the caudal body axis for non-mutant and curly tail mouse embryos during the period of caudal neural tube closure.

During the period of early organogenesis the mouse embryo has a curved body shape, which is thought to interact with ongoing developmental processes. Curly tail is a mouse mutant causing spina bifida, in which aberrant axial curvature is considered to be responsible for a delay in the closure of the posterior neuropore (PNP). Since detailed descriptions of axial curvature have never been made in either the normal or the mutant embryo, the onset and development of the aberrant axial curvature in the curly tail embryo are unknown. In the present study, axial curvature and segmental growth during closure of the PNP are described using circle segments at each somite level in two non-mutant mouse strains. Using the radius and angle of the segments as parameters, CD-1 and Balb/c mouse embryos showed maxima of curvature at the levels of the limb buds. Throughout development, a general axial unbending occurred that was due to a level-specific combination of general outgrowth and other factors. A marked additional decrease in the axial curvature was spatially and temporally related to the final closure of the PNP, indicating that this decrease of curvature facilities the final closure of the PNP. In the curly tail embryo the segment parameter radius was used to relate the axial curvature to an aberrant neural tube closure pattern. These embryos exhibited an enhanced curvature over the entire neuropore region as soon as a delay in the PNP closure could be distinguished. A steep decrease in curvature during final closure of the PNP did also occur, but at a more caudal level. Both the axial level of straightening and the rate of curvature were normalized at advanced developmental stages. The aberrant spatio-temporal curvature pattern in the curly tail mouse embryo indicates that both the rate of curvature and the axial level of unbending are important for a correct PNP closure.

Exploring the role of Chlamydia pneumoniae in cardiovascular disease: a narrative review.

An overwhelming number of studies have suggested that Chlamydia pneumoniae infections play a role in the development of atherosclerosis. Several, but not all, seroepidemiological studies have shown that C. pneumoniae antibodies may be related to the development of atherosclerotic disease. Additionally, C. pneumoniae seems to be present in atherosclerotic but not in healthy vascular tissue. Experimental studies have suggested a number of molecular mechanisms by which vascular C. pneumoniae infection might stimulate atherosclerosis development. Alternatively, nonvascular C. pneumoniae infection may cause clinically relevant atherosclerosis-related cardiovascular events through the systemic effects of chronic infection. Genetic variation may account for individual differences in susceptibility to the proatherogenic effects of C. pneumoniae infection. Despite the suggested role of infection in atherosclerosis, antibiotics seem to have no place in the secondary prevention of atherosclerosis-related cardiovascular events. The present narrative review evaluates the role of C. pneumoniae infections in the development of cardiovascular disease.

Systemic dilation diathesis in patients with abdominal aortic aneurysms: a role for matrix metalloproteinase-9?

INTRODUCTION: Accumulating evidence suggests that patients with abdominal aortic aneurysm (AAA) suffer from a systemic dilating condition affecting all arteries. Matrix metalloproteinases (MMPs) and their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), appear to be involved in aneurysm formation, as evidenced by increased aortic tissue MMP activity and plasma MMP levels in patients with AAA. Hypothesizing that an imbalance in plasma MMP/TIMP level might be associated with a systemic dilation diathesis, we studied mechanical vessel wall properties of non-affected arteries of patients with either AAA or aorto-iliac obstructive lesions in association with plasma MMP-9 and TIMP-1 levels. METHODS: Twenty-two patients with AAA and 12 with aorto-iliac occlusive disease (AOD) were included. Diastolic diameter (d) and distension (Deltad) were measured at the level of the common carotid artery (CCA) and suprarenal aorta (SA) using ultrasonography. Distensibility (DC) and compliance (CC) were calculated from d, Deltad and brachial pulse pressure. Plasma MMP-9 and TIMP-1 were determined with specific immunoassays. RESULTS: The average (+/-SD) age was 72.3+/-5.6 and 65.0+/-8.2 years for the AAA and AOD patients, respectively, (P=0.005). CCA diameter was 9.1+/-1.3mm in AAA patients and AOD 7.8+/-1.4mm in AOD patients, P=0.009. This difference persisted after correction for age. Plasma MMP-9 and TIMP-1 did not differ significantly between AAA and AOD patients. In the total 34 patients, the MMP-9/TIMP-1 ratio was correlated inversely with distensibility (r=-0.74, P=0.002) and to compliance (r=-0.58, P=0.024) of the suprarenal aorta. CONCLUSIONS: The CCA diameter was larger in AAA patients compared to AOD patients. MMP-9/TIMP-1 ratio was associated with decreased distensibility and compliance of the suprarenal aorta. These data support the idea that AAA patients exhibit a systemic dilation diathesis, which might be attributable to MMP/TIMP imbalances.

Secondary prevention of atherosclerosis through chlamydia pneumoniae eradication (SPACE Trial): a randomised clinical trial in patients with peripheral arterial disease.

BACKGROUND: Sero-epidemiological and experimental studies suggest that Chlamydia pneumoniae infections play an important role in the development of atherosclerosis. Clinical trials have shown contradictory results regarding the efficacy of antibiotics to prevent atherosclerosis-related complications in patients with coronary artery disease. Our aim was to study the effect of a short course of azithromycin on the incidence of cardiovascular events and peripheral vascular function in patients with stable peripheral arterial disease (PAD). PATIENTS AND METHODS: Five hundred and nine PAD-patients were randomised to receive either a 3-day course of azithromycin (500 mg daily) or placebo, with 2 years of follow-up. C. pneumoniae serology was determined at baseline. Clinical endpoints were death, coronary events (myocardial infarction, unstable angina, and/or coronary revascularization procedures), cerebral events (stroke, TIA, and/or carotid endarterectomy) and peripheral arterial complications (increased PAD-symptoms with decreased ankle-brachial index (ABPI, 0.1-point decrease after 12 months), and/or peripheral revascularization procedures). RESULTS: Five hundred and nine patients (160 women) with an atherosclerotic risk factor profile were randomised, 257 patients to azithromycin and 252 to placebo. Four hundred and forty nine patients (88%) had intermittent claudication and 60 (12%) had critical limb ischemia. By 24-month follow up, 182 patients (36%) developed 252 complications (45 deaths, 34 coronary events, 34 cerebral events and 139 peripheral arterial complications). C. pneumoniae IgA-titres were associated with the development of cardiovascular events. Nevertheless, the number of complications (131 in the azithromycin group vs. 121 in the placebo group) and the number of patients that developed complications (98 (38%) in the azithromycin vs. 84 (33%) in the placebo group) was comparable in both treatment groups. Life table analysis showed no effect of azithromycin on survival or ABPI. CONCLUSION: A short-term course of azithromycin offers no benefits for survival or ankle pressure in PAD-patients.

The Pruitt-Inahara shunt maintains mean middle cerebral artery velocities within 10% of preoperative values during carotid endarterectomy.

OBJECTIVE: The purpose of this study was to assess the ability of the Pruitt-Inahara shunt to maintain adequate middle cerebral artery velocities during carotid endarterectomy. STUDY DESIGN: Prospectively collected data recorded during 548 carotid endarterectomies performed at a single university hospital were analyzed to look at changes in cerebral blood flow velocities at different stages during the procedure. Parallel data relating to blood pressure and end-tidal carbon dioxide were also examined. RESULTS: During the first carotid artery cross clamp, middle cerebral artery velocity fell by 42%. A total of 169 patients (31%) had velocities that fell below 15 cm/s (electrical activity in the brain becomes altered below this level). After shunt insertion, only 2% of patients had middle cerebral artery velocities less than 15 cm/s. In only one patient was the velocity less than 10 cm/s. Increased systolic or diastolic blood pressure raised flow through the shunt significantly (P =.001). When two criteria used for selective shunt use were compared, only a moderate correlation was found between absolute middle cerebral artery velocity after carotid cross clamping and percentage change in middle cerebral artery velocity relative to preclamp values. CONCLUSIONS: The Pruitt-Inahara shunt is able to maintain adequate middle cerebral artery velocity in 98% of patients undergoing carotid endarterectomy. Alterations in blood pressure can significantly affect flow through the shunt.