[A man with abdominal pain and nausea]. / Een man met buikpijn en misselijkheid.

A 63-year-old man with a history of orthotopic liver transplantation was presented to the emergency department with progressive right flank pain and nausea. On physical examination, we found a hernia cicatricalis that was painful on palpation. An abdominal CT scan showed acute perforated appendicitis, located in a hernia cicatricalis.

RP105 deficiency aggravates cardiac dysfunction after myocardial infarction in mice.

BACKGROUND: Toll-like receptor-4 (TLR4), a receptor of the innate immune system, is suggested to have detrimental effects on cardiac function after myocardial infarction (MI). RP105 (CD180) is a TLR4 homolog lacking the intracellular signaling domain that competitively inhibits TLR4-signaling. Thus, we hypothesized that RP105 deficiency, by amplifying TLR4 signaling, would lead to aggravated cardiac dysfunction after MI. METHODS AND RESULTS: First, whole blood from RP105-/- and wild-type (WT) male C57Bl/6N mice was stimulated with LPS, which induced a strong inflammatory TNFα response in RP105-/- mice. Then, baseline heart function was assessed by left ventricular pressure-volume relationships which were not different between RP105-/- and WT mice. Permanent ligation of the left anterior descending coronary artery was performed to induce MI. Infarct sizes were analyzed by (immuno)histology and did not differ. Fifteen days post MI heart function was assessed and RP105-/- mice had significantly higher heart rate (+21%, P<0.01), end systolic volume index (+57%, P<0.05), end systolic pressure (+22%, P<0.05) and lower relaxation time constant tau (-12%, P<0.05), and a tendency for increased end diastolic volume index (+42%, P<0.06), compared to WT mice. In the area adjacent to the infarct zone, compared to the healthy myocardium, levels of RP105, TLR4 and the endogenous TLR4 ligand fibronectin-EDA were increased as well as the number of macrophages, however this was not different between both groups. CONCLUSION: Deficiency of the endogenous TLR4 inhibitor RP105 leads to an enhanced inflammatory status and more pronounced cardiac dilatation after induction of MI, underscoring the role of the TLR4 pathway in post-infarction remodeling.

A limited role for regulatory T cells in post-ischemic neovascularization.

Recently, it was demonstrated that arteriogenesis is enhanced in mice deficient in regulatory T cells (CD4(+) CD25(+) FoxP3(+) T cell), which can suppress effector T cell responses. The present study investigates the effects of these regulatory T cells on arteriogenesis in more detail by either specific expanding or depleting regulatory T cells. Hind limb ischemia was induced by electro-coagulation of the femoral artery in mice. Regulatory T cells were either expanded by injecting mice with a complex of interleukin (IL)-2 with the IL-2 monoclonal antibody JES6-1, or depleted by anti-CD25 antibody or diphtheria toxin injections in DEREG mice (depletion of regulatory T cells). Blood flow restoration was monitored using laser Doppler perfusion imaging. Collateral arteries were visualized by immunohistochemistry. Regulatory T cell expansion led to a moderate though significant suppression of blood flow restoration after ischemia induction. Surprisingly, depletion of regulatory T cells resulted in minor increase on blood flow recovery. However, collateral and capillary densities in the post-ischemic skeletal muscle were significantly increased in DEREG mice depleted for regulatory T cells. The presence of regulatory T cells after ischemia induction when analysed in non-depleted DEREG mice could be demonstrated by green fluorescent protein staining only in lymph nodes in the ischemic area, and not in the ischemic muscle tissue. The current study demonstrates that, even under conditions of major changes in regulatory T cell content, the contribution of regulatory T cells to the regulation of the arteriogenic response is only moderate.

Variations in surgical procedures for hind limb ischaemia mouse models result in differences in collateral formation.

OBJECTIVE: To identify the optimal mouse model for hind limb ischaemia, which offers a therapeutic window that is large enough to detect improvements of blood flow recovery, for example, using cell therapies. MATERIALS AND METHODS: Different surgical approaches were performed: single coagulation of femoral and iliac artery, total excision of femoral artery and double coagulation of femoral and iliac artery. Blood flow restoration was analysed with laser Doppler perfusion imaging (LDPI). Immuno-histochemical stainings, angiography and micro-computed tomography (CT) scans were performed for visualisation of collaterals in the mouse. RESULTS: Significant differences in flow restoration were observed depending on the surgical procedure. After single coagulation, blood flow already restored 100% in 7 days, in contrast to a significant delayed flow restoration after double coagulation (54% after 28 days, P<0.001). After total excision, blood flow was 100% recovered within 28 days. Compared with total excision, double coagulation displayed more pronounced corkscrew phenotype of the vessels typical for collateral arteries on angiographs. CONCLUSION: The extent of the arterial injury is associated with different patterns of perfusion restoration. The double coagulation mouse model is, in our hands, the best model for studying new therapeutic approaches as it offers a therapeutic window in which improvements can be monitored efficiently.

A comparison of the Doppler-derived maximal systolic acceleration versus the ankle-brachial pressure index or detecting and quantifying peripheral arterial occlusive disease in diabetic patients.

AIM: The aim of this study was to assess the diagnostic accuracy of the Doppler derived maximal systolic acceleration (ACCmax) as a novel technique for evaluating peripheral arterial occlusive disease (PAOD) in patients with diabetes mellitus, who are known for a falsely elevated ankle-brachial index (ABI). METHODS: In this retrospective analysis ACCmax was measured at ankle level in a series of 163 consecutive patients referred to the vascular laboratory for initial assessment of PAOD. Patients were classified according to the presence or absence of diabetes. In the non-diabetic patients PAOD was defined as ABI < or =0.90. This group was used to establish the association between ACCmax and ABI in a linear regression model. The result was then used to predict the presence or absence of PAOD in the diabetic patients. RESULTS: The authors examined 301 lower limbs. The study group consisted of 166 limbs of patients without diabetes and 135 limbs of patients with diabetes. PAOD was present in 52% of limbs in the nondiabetic group versus 59% of limbs in the diabetic group (ABI < or =0.90, or in case of non-compliant vessels toe-brachial index (TBI) < or =0.70). An ACCmax cut-off value of >10 m/s2 was found to be highly predictive for the exclusion of PAOD (negative predictive value 95%). In addition, the ACCmax cut-off value of <6.5 m/s2 was highly predictive for the detection of PAOD (positive predictive value 99%). A strong quadratic association was found between ACCmax and ABI in the non-diabetic group (R2=0.85). In the diabetic patients R2 values were 0.81 and 0.79 after ABI and TBI measurement respectively. CONCLUSION: DUS-derived ACCmax is an accurate marker that could offer significant benefits for the diagnosis of PAOD, especially in diabetic patients.