Prediction model for pneumonia in primary care patients with an acute respiratory tract infection: role of symptoms, signs, and biomarkers.

BACKGROUND: Diagnosing pneumonia can be challenging in general practice but is essential to distinguish from other respiratory tract infections because of treatment choice and outcome prediction. We determined predictive signs, symptoms and biomarkers for the presence of pneumonia in patients with acute respiratory tract infection in primary care. METHODS: From March 2012 until May 2016 we did a prospective observational cohort study in three radiology departments in the Leiden-The Hague area, The Netherlands. From adult patients we collected clinical characteristics and biomarkers, chest X ray results and outcome. To assess the predictive value of C-reactive protein (CRP), procalcitonin and midregional pro-adrenomedullin for pneumonia, univariate and multivariate binary logistic regression were used to determine risk factors and to develop a prediction model. RESULTS: Two hundred forty-nine patients were included of whom 30 (12%) displayed a consolidation on chest X ray. Absence of runny nose and whether or not a patient felt ill were independent predictors for pneumonia. CRP predicts pneumonia better than the other biomarkers but adding CRP to the clinical model did not improve classification (- 4%); however, CRP helped guidance of the decision which patients should be given antibiotics. CONCLUSIONS: Adding CRP measurements to a clinical model in selected patients with an acute respiratory infection does not improve prediction of pneumonia, but does help in giving guidance on which patients to treat with antibiotics. Our findings put the use of biomarkers and chest X ray in diagnosing pneumonia and for treatment decisions into some perspective for general practitioners.

Vitamin D serum levels are cross-sectionally but not prospectively associated with late-life depression.

OBJECTIVE: The evidence for a prospective association of vitamin D deficiency with the occurrence of late-life depression is limited. We aimed to study the long-term association between vitamin D serum levels and depression in a large population-based study of older adults. METHOD: We included 3251 participants from the Rotterdam Study, aged 55 and older with 32 400 person-years follow-up for depression. Baseline 25-hydroxyvitamin D (25(OH)D) serum levels were analyzed continuously and categorically. Repeated depressive symptoms' questionnaire assessments were used to assess the change of depressive symptoms. Semistructured psychiatric interviews, and GP records were used to assess incident major depressive disorder according to DSM-IV criteria. RESULTS: Low serum vitamin D levels were cross-sectionally associated with more depressive symptoms. However, low 25(OH)D serum levels were not prospectively associated with change of depressive symptoms (unstandardized beta = 0.02, 95% CI = -0.23; 0.26) or incident MDD (hazard ratio = 0.95, 95% CI = 0.86; 1.05). CONCLUSION: We observed a cross-sectional but no prospective association between serum vitamin D levels and depression. A cross-sectional association in the absence of the longitudinal association can mostly be attributed to reverse causality or residual confounding. Probably, vitamin D deficiency is not an independent risk factor for depression but co-occurs with late-life depression.

The long-term risk of recognized and unrecognized myocardial infarction for depression in older men.

BACKGROUND: The association between myocardial infarction (MI) and depression is well described. Yet, the underlying mechanisms are unclear and the contribution of psychological factors is uncertain. We aimed to determine the risk of recognized (RMI) and unrecognized (UMI) myocardial infections on depression, as both have a similar impact on cardiovascular health but differ in psychological epiphenomena. METHOD: Participants of the Rotterdam Study, 1823 men aged ⩾55 years, were followed for the occurrence of depression. RMI and UMI were ascertained using electrocardiography and medical history at baseline. We determined the strength of the association of RMI and UMI with mortality, and we studied the relationship of RMI and UMI with depressive symptoms and the occurrence of major depression. RESULTS: The risk of mortality was similar in men with RMI [adjusted hazard ratio (aHR) 1.71, 95% confidence interval (CI) 1.45-2.03] and UMI (aHR 1.58, 95% CI 1.27-1.97). Men with RMI had on average [unstandardized regression coefficient (B) 1.14, 95% CI 0.07-2.21] higher scores for depressive symptoms. By contrast, we found no clear association between UMI and depressive symptoms (B 0.55, 95% CI -0.51 to 1.62) in men. Analysis including occurrence of major depression as the outcome were consistent with the pattern of association. CONCLUSION: The discrepant association of RMI and UMI with mortality compared to depression suggests that the psychological burden of having experienced an MI contributes to the long-term risk of depression.

Antidepressants and heart-rate variability in older adults: a population-based study.

BACKGROUND: Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) may be associated with lower heart rate variability (HRV), a condition associated with increased mortality risk. We aimed to investigate the association between TCAs, SSRIs and HRV in a population-based study. METHOD: In the prospective Rotterdam Study cohort, up to five electrocardiograms (ECGs) per participant were recorded (1991-2012). Two HRV variables were studied based on 10-s ECG recordings: standard deviation of normal-to-normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD). We compared the HRV on ECGs recorded during use of antidepressants with the HRV on ECGs recorded during non-use of any antidepressant. Additionally, we analysed the change in HRV on consecutive ECGs. Those who started or stopped using antidepressants before the second ECG were compared with non-users on two ECGs. RESULTS: We included 23 647 ECGs from 11 729 participants (59% women, mean age 64.6 years at baseline). Compared to ECGs recorded during non-use of antidepressants (n = 22 971), SDNN and RMSSD were lower in ECGs recorded during use of TCAs (n = 296) and SSRIs (n = 380). Participants who started using TCAs before the second ECG had a decrease in HRV and those who stopped had an increase in HRV compared to consistent non-users (p < 0.001). Starting or stopping SSRIs was not associated with HRV changes. CONCLUSION: TCAs were associated with a lower HRV in all analyses, indicating a real drug effect. For SSRIs the results are mixed, indicating a weaker association, possibly due to other factors.

Randomised trial of no hydration vs. sodium bicarbonate hydration in patients with chronic kidney disease undergoing acute computed tomography-pulmonary angiography.

BACKGROUND: Hydration to prevent contrast-induced acute kidney injury (CI-AKI) induces a diagnostic delay when performing computed tomography-pulmonary angiography (CTPA) in patients suspected of having acute pulmonary embolism. AIM: To analyze whether withholding hydration is non-inferior to sodium bicarbonate hydration before CTPA in patients with chronic kidney disease (CKD). METHODS: We performed an open-label multicenter randomized trial between 2009 and 2013. One hundred thirty-nine CKD patients were randomized, of whom 138 were included in the intention-to-treat population: 67 were randomized to withholding hydration and 71 were randomized to 1-h 250 mL 1.4% sodium bicarbonate hydration before CTPA. Primary outcome was the increase in serum creatinine 48-96 h after CTPA. Secondary outcomes were the incidence of CI-AKI (creatinine increase > 25%/> 0.5 mg dL(-1) ), recovery of renal function, and the need for dialysis within 2 months after CTPA. Withholding hydration was considered non-inferior if the mean relative creatinine increase was ≤ 15% compared with sodium bicarbonate. RESULTS: Mean relative creatinine increase was -0.14% (interquartile range -15.1% to 12.0%) for withholding hydration and -0.32% (interquartile range -9.7% to 10.1%) for sodium bicarbonate (mean difference 0.19%, 95% confidence interval -5.88% to 6.25%, P-value non-inferiority < 0.001). CI-AKI occurred in 11 patients (8.1%): 6 (9.2%) were randomized to withholding hydration and 5 (7.1%) to sodium bicarbonate (relative risk 1.29, 95% confidence interval 0.41-4.03). Renal function recovered in 80.0% of CI-AKI patients within each group (relative risk 1.00, 95% confidence interval 0.54-1.86). None of the CI-AKI patients developed a need for dialysis. CONCLUSION: Our results suggest that preventive hydration could be safely withheld in CKD patients undergoing CTPA for suspected acute pulmonary embolism. This will facilitate management of these patients and prevents delay in diagnosis as well as unnecessary start of anticoagulant treatment while receiving volume expansion.

Utilization patterns of antidepressants between 1991 and 2011 in a population-based cohort of middle-aged and elderly.

BACKGROUND: In middle-aged and older patients in whom antidepressant use increased in last decades, patterns of use might be of concern The objective of this study was to investigate the patterns of prevalence, incidence and duration of antidepressant use in an ageing population. METHODS: All participants (aged>45 years) from the population-based Rotterdam Study were followed from January 1st 1991 until death, loss to follow-up, or end of the study period (December 31st 2011). Antidepressant drug dispensing, based on pharmacy records, were subdivided into Tricyclic Antidepressants (TCAs), Selective Serotonin Reuptake Inhibitors (SSRIs) and other antidepressants. One-year prevalence, 5-year incidence and duration of antidepressant use were calculated. RESULTS: Yearly prevalence of antidepressant use increased from 3.9% in 1991 to 8.3% of the population in 2011. The increase in SSRI use was 5.8-fold, whereas use of other antidepressants doubled and TCA use remained stable over time. Incidence of all antidepressants decreased from 23.9 to 14.2 per 1000 person-years between 1992 and 2011. The duration of a first treatment episode increased over time. CONCLUSION: Despite the prevalence of antidepressant use increased over time, incidence did not, which is most likely explained by a longer treatment duration and recurrent episodes.

[A patient with hypoaesthesia of the mandible]. / Een patiënt met hypesthesie in de mandibula.

In a patient with hypoaesthesia of the central region of the mandible, no oral cause could be found which could explain his complaint. Further examination by a neurologist and a specialist in internal medicine revealed the numb chin syndrome. The syndrome was caused by meningeal localisation of a high-grade B-cell lymphoma stade IV. After intensive chemotherapy and radiotherapy of the skull, the complaints disappeared.

Predicting the need for radiologic imaging in adults with febrile urinary tract infection.

BACKGROUND: Radiologic evaluation of adults with febrile urinary tract infection (UTI) is frequently performed to exclude urological disorders. This study aims to develop a clinical rule predicting need for radiologic imaging. METHODS: We conducted a prospective, observational study including consecutive adults with febrile UTI at 8 emergency departments (EDs) in the Netherlands. Outcomes of ultrasounds and computed tomographs of the urinary tract were classified as "urgent urological disorder" (pyonephrosis or abscess), "nonurgent urologic disorder," "normal," and "incidental nonurological findings." Urgent and nonurgent urologic disorders were classified as "clinically relevant radiologic findings." The data of 5 EDs were used as the derivation cohort, and 3 EDs served as the validation cohort. RESULTS: Three hundred forty-six patients were included in the derivation cohort. Radiologic imaging was performed for 245 patients (71%). A prediction rule was derived, being the presence of a history of urolithiasis, a urine pH ≥7.0, and/or renal insufficiency (estimated glomerular filtration rate, ≤40 mL/min/1.73 m(3)). This rule predicts clinically relevant radiologic findings with a negative predictive value (NPV) of 93% and positive predictive value (PPV) of 24% and urgent urological disorders with an NPV of 99% and a PPV of 10%. In the validation cohort (n = 131), the NPV and PPV for clinically relevant radiologic findings were 89% and 20%, respectively; for urgent urological disorders, the values were 100% and 11%, respectively. Potential reduction of radiologic imaging by implementing the prediction rule was 40%. CONCLUSIONS: Radiologic imaging can selectively be applied in adults with febrile UTI without loss of clinically relevant information by using a simple clinical prediction rule.

Debunking the myth of the hard-to-reach farmer: effective communication on udder health.

Worldwide, programs to control mastitis are implemented using different strategies to reach farmers. Even though education materials and best practices may be technically optimal, they need to be used to be successful. Thus, effective communication with farmers is essential in order to change their behavior and to improve their farm management. During a Dutch national mastitis control program, a substantial number of farmers seemed to be hard to reach with information on udder health. Consequently, this study was designed to provide insight into the attitude and motivation of such farmers. In the period of October 2007 to July 2008, 24 in-depth, semistructured interviews were conducted with farmers whose veterinarians considered to be difficult to approach with advice on udder health management (8 practices, 3 farmers from each practice). The interviews included questions about the farms and the farmers, their attitude and behavior regarding mastitis, and their information sources and social environment. The results show that so-called hard-to-reach farmers were not always badly informed about udder health and did not always experience problems with mastitis. These ostensibly unreachable farmers were not a homogeneous group, but rather could be divided into 4 categories based on their trust in external information sources regarding mastitis and their orientation toward the outside world: proactivists, do-it-yourselfers, wait-and-see-ers, and reclusive traditionalists. There are ample opportunities to reach hard-to-reach farmers, provided that the communication strategies are tailored to their specific needs. There is especially much to gain in communication with do-it-yourselfers and wait-and-see-ers, but this demands a more proactive role on the part of veterinarians and extension specialists. Different types of farmers need to be approached in different ways and through different channels with information on udder health. Consequently, this study can contribute to the optimization of future programs designed to control and prevent diseases.

[Guideline 'Precautionary measures for contrast media containing iodine']. / Richtlijn 'Voorzorgsmaatregelen bij jodiumhoudende contrastmiddelen'.

Annually, 0.5-1 million injections of contrast media containing iodine are administered in the Netherlands. Almost all contrast media nowadays are low-osmolar and nonionic. Nevertheless, the development ofcontrast-induced nephropathy is still a relevant clinical problem. Through an initiative by the Radiological Society of the Netherlands and with aid of the Dutch Institute for Healthcare Improvement (CBO), a guideline was conceived for the intravascular use of iodine-containing contrast media, based on recent scientific literature. The guideline defines the risk factors for contrast-induced nephropathy. One of the major risk factors is an impaired renal function. It is important to measure the glomerular filtration rate (GFR) in patients with a possible impaired kidney function, preferably by using the 'Modification of diet in renal disease' (MDRD)-study formula. The key measures for avoidance of contrast nephropathy are: limiting the amount of contrast agent used and to assure good hydration, by infusion of sodium chloride 0.9% 12-16 ml/kg body weight, both prior to and after contrast infusion. If time is limited, intravenous administration of sodium bicarbonate is an option. The guideline recommends discontinuation of metformin use from the day of contrast injection, if the GFR < 60 ml/min/1.73 m2, and to restart metformin 2 days following contrast infusion providing the GFR has not significantly deteriorated. Only in the case of previous moderate or severe adverse reactions to contrast media, prophylaxis with corticosteroids and antihistamines is recommended. Iodine allergy or an atopic condition is not a contraindication for the use of iodine-containing contrast media, and no prophylaxis is required. No specific measures are indicated in case of hyperthyroidism, acute pancreatitis, or phaeochromocytoma. Injection of contrast media is not contraindicated in case of pregnancy or lactation.

[Two patients with fever, chills and pain in the right upper abdominal quadrant accompanied by hyperbilirubinaemia: pylephlebitis]. / Twee patiënten met koorts, koude rillingen en pijn rechts in de bovenbuik en hyperbilirubinemie: pyleflebitis.

Two male patients aged 55 and 77 years, respectively, presented to the casualty department with fever, chills and right abdominal upper quadrant tenderness. They also had hyperbilirubinaemia. Based on CT scan findings and blood cultures yielding Bacteroides fragilis, a diagnosis of pylephlebitis (septic thrombophlebitis of the mesenteric veins and/or the portal vein) was made. This is a condition with a mortality rate of 10-70%. Primary sources such as diverticulitis are often seen in patients with pylephlebitis, in which bacteria are drained by the mesenteric veins and cause a thrombus in the portal system. In the two patients no primary focus was detected. They were treated with intravenous antibiotic therapy followed by oral antibiotics, and were discharged in good health. Pylephlebitis can be complicated by liver abscesses. Treatment consists of broad-spectrum antibiotics which are adjusted based on the blood cultures results. The duration of treatment is between two and six weeks, depending on the presence of liver abscesses. In patients with abscesses that cannot be drained, longer treatment may be indicated.

Plasma secretory leukocyte protease inhibitor in febrile patients.

OBJECTIVES: Secretory leukocyte protease inhibitor (SLPI) forms an integral part of the lung's defence, by its antimicrobial activity and by its ability to neutralize serine proteases that are released by granulocytes into the inflammatory exudate. Here, we investigate in febrile patients admitted to hospital whether plasma SLPI can serve as a marker of lung infection. METHODS: We prospectively determined the SLPI concentration in 152 febrile patients (median 73 [inter-quantile range (IQR): 58-82] year; 50% male) admitted to hospital because of infection of the airways (n = 44) or pneumonia (n = 108; i.e. consolidation on chest X-ray), and in 48 febrile patients (78 [IQR: 71-85] year; 52% male) admitted because of pyelonephritis, as well as afebrile age-matched controls (n = 38). In addition, erythrocyte sedimentation rate (ESR), peripheral blood leukocytes, plasma TNFalpha and IL-10, and parameters of the APACHE-II score were determined on admission. RESULTS: In febrile patients, SLPI was significantly increased (P < 0.001) compared with afebrile controls (63 [IQR: 50-76] ng/mL): plasma SLPI (113 [IQR: 83-176] ng/mL) was highest (P < 0.005) in patients with pneumonia compared with other groups (88 [IQR: 70-118] ng/mL). Only in patients with pneumonia, bacteremia significantly increased (P < 0.01) SLPI concentrations. Using a radiological classification of pulmonary infiltrates based on their size, it was found that plasma SLPI was proportional to the extent of lung tissue involved: the median concentration increased from 95 [IQR: 74-139] ng/mL in unilateral segmental consolidation up to 271 [IQR: 180-460] ng/mL in bilateral lobar consolidations. In a multivariate analysis, the association between SLPI and extent of consolidation was about two-fold stronger than, and independent of, the association between SLPI and erythrocyte sedimentation rate, TNFalpha, and parameters of the composite APACHE-II score, such as heart rate and blood pressure, that reflect severity of illness. CONCLUSION: SLPI is an indicator of the presence and extent of pneumonia in febrile patients admitted to hospital. In patients with an infection with its primary source located outside the lung, plasma SLPI likely reflects the mucosal response to circulating inflammatory mediators reflecting severity of illness.

Constitutive disease resistance requires EDS1 in the Arabidopsis mutants cpr1 and cpr6 and is partially EDS1-dependent in cpr5.

The systemic acquired resistance (SAR) response in Arabidopsis is characterized by the accumulation of salicylic acid (SA), expression of the pathogenesis-related (PR) genes, and enhanced resistance to virulent bacterial and oomycete pathogens. The cpr (constitutive expressor of PR genes) mutants express all three SAR phenotypes. In addition, cpr5 and cpr6 induce expression of PDF1.2, a defense-related gene associated with activation of the jasmonate/ethylene-mediated resistance pathways. cpr5 also forms spontaneous lesions. In contrast, the eds1 (enhanced disease susceptibility) mutation abolishes race-specific resistance conferred by a major subclass of resistance (R) gene products in response to avirulent pathogens. eds1 plants also exhibit increased susceptibility to virulent pathogens. Epistasis experiments were designed to explore the relationship between the cpr- and EDS1-mediated resistance pathways. We found that a null eds1 mutation suppresses the disease resistance phenotypes of both cpr1 and cpr6. In contrast, eds1 only partially suppresses resistance in cpr5, leading us to conclude that cpr5 expresses both EDS1-dependent and EDS1-independent components of plant disease resistance. Although eds1 does not prevent lesion formation on cpr5 leaves, it alters their appearance and reduces their spread. This phenotypic difference is associated with increased pathogen colonization of cpr5 eds1 plants compared to cpr5. The data allow us to place EDS1 as a necessary downstream component of cpr1- and cpr6-mediated responses, but suggest a more complex relationship between EDS1 and cpr5 in plant defense.

Genetic analysis of plant disease resistance pathways.

Plant disease resistance (R) genes are introduced into high yielding crop varieties to improve resistance to agronomically important pathogens. The R gene-encoded proteins are recognitionally specific, interacting directly or indirectly with corresponding pathogen avirulence (avr) determinants, and are therefore under strong diversifying selection pressure to evolve new recognition capabilities. Genetic analyses in different plant species have also revealed more broadly recruited resistance signalling genes that provide further targets for manipulation in crop improvement strategies. Understanding the processes that regulate both plant-pathogen recognition and the induction of appropriate defences should provide fresh perspectives in combating plant disease. Many recent studies have utilized the model plant, Arabidopsis thaliana. Here, mutational screens have identified genes that are required for R gene function and for restriction of pathogen growth in compatible plant-pathogen interactions. Genetic analyses of these plant mutants suggest that whilst signalling pathways are conditioned by particular R protein structural types they are also influenced by pathogen lifestyle. Two Arabidopsis defence signalling genes, EDS1 and PAD4, are required for the accumulation of salicylic acid, a phenolic molecule required for systemic immunity. The cloning, molecular and biochemical characterization of these components suggests processes that may be important in their disease resistance signalling roles.

Pulsatile wall motion and blood pressure in aneurysms with open and thrombosed endoleaks--comparison of a wall track system and M-mode ultrasound scanning: an in vitro and animal study.

OBJECTIVE: Pulsatile wall motion has been suggested as a means by which to evaluate abdominal aortic aneurysms after exclusion from the circulation to determine whether the treatment has been effective. The objective of this study was to investigate the relations between pulsatile wall motion and both the mean and pulse pressures within the aneurysmal sac for both patent and thrombosed endoleaks. Furthermore, we compared the measurements of pulsatile wall motion by means of M-mode ultrasound scanning and a wall track system to determine the most reliable technique. METHODS: First, interobserver and intraobserver variability of M-mode ultrasound scan measurements was determined at different pressure levels in a cow iliac artery placed in an in vitro circulation. M-mode ultrasound scanning and a wall track system were compared in the same model. Second, in an animal experiment, an aneurysm and endoleak model with both patent and thrombosed endoleaks was created. Systemic and aneurysmal mean and pulse pressures were recorded synchronically with pulsatile wall motion by means of M-mode ultrasound scanning and a wall track system. RESULTS: The intraobserver and interobserver variability values for M-mode ultrasound scan measurement in vitro were 0.11 mm (SD = 0.10 mm) and 0.15 mm (SD = 0.13 mm), respectively. In the animal study, a significant difference existed with respect to the level of pulse pressure within the aneurysmal sac between the group with pulsatile wall motion and the group without such motion (P <.0001). The presence of pulsatile wall motion was not correlated with the level of aneurysmal mean pressure. The level of pulsatile wall motion determined by means of M-mode ultrasound scanning correlated well with the level determined by means of the wall track system (r = 0. 74; P =.01). For the level of pulsatile wall motion determined by means of M-mode ultrasound scanning, a significant difference between patent and thrombosed endoleaks existed (P =.04). For detecting endoleaks, the sensitivity and specificity of pulsatile wall motion as determined by means of the wall track system were 52% and 100%, respectively, and the sensitivity and specificity of pulsatile wall motion as determined by means of M-mode ultrasound scanning were 64% and 67%, respectively. For the detection of pulse pressure in the aneurysmal sac, the sensitivity and specificity of pulsatile wall motion as determined by means of the wall track system were 76% and 100%, respectively, and the sensitivity and specificity of pulsatile wall motion as determined by means of M-mode ultrasound scanning were 90% and 71%, respectively. CONCLUSIONS: We found that pulsatile wall motion is correlated with aneurysmal pulse pressure but not with the mean level of pressure inside the aneurysm. Although measurements of pulsatile wall motion are of great theoretic value when groups of patients who have undergone endovascular aneurysm repair are being compared, this method appears to be unreliable in a clinical setting with respect to determining whether the aneurysmal sac is still pressurized in individual patients.

Experimental study of the influence of endoleak size on pressure in the aneurysm sac and the consequences of thrombosis.

BACKGROUND: This was an experimental study of endovascular aortic surgery, looking at the relationship between the size of an endoleak, pressure in the aneurysm sac and the effect of thrombosis produced by coagulation. METHODS: In three pigs, 16 saccular aneurysms were connected to the aorta by various side branches with different diameters and lengths ('endoleaks'). Mean and pulse pressures were measured in the systemic circulation as well as in the aneurysm sac during the experiment. Duplex ultrasonography was used to determine whether the endoleak and the aneurysm were patent or thrombosed. Thrombosis was influenced by systemic tranexamic acid, fibrinogen in the aneurysm sac, Gelfoam in both endoleak and aneurysm sac, and by Histoacryl glue in the endoleak. RESULTS: With an open endoleak, the mean pressure in the aneurysm and the aorta was identical. Mean aneurysm pressure was lower with a thrombosed endoleak and was related to the diameter of the endoleak. Pulse pressure was recorded in the aneurysm sac when there was an open endoleak and a non-thrombosed aneurysm, and was related to the diameter of the open endoleak. Thrombosed endoleaks never produced pulse pressure in the aneurysm. If Histoacryl and Gelfoam induced thrombosis of the endoleak, the decrease in mean aneurysm pressure was identical to that resulting from the spontaneous thrombosis of endoleaks. CONCLUSION: An open endoleak results in systemic arterial pressure in the aneurysm sac. Pulse pressure is detected if the aneurysm is patent, but absent if there is complete or partial thrombosis of the aneurysm. Endoleak thrombosis, either spontaneous or by embolization, is accompanied by a decrease in mean pressure and the absence of pulse pressure in the aneurysm sac. The extent to which these experimental findings are comparable to the clinical situation represents a field of further research.

Unravelling R gene-mediated disease resistance pathways in Arabidopsis.

Abstract Molecular genetic approaches were adopted in the model crucifer, Arabidopsis thaliana, to unravel components of RPP5- and RPP1-mediated disease resistance to the oomycete pathogen, Peronospora parasitica. The products of RPP5 and three genes comprising the RPP1 complex locus belong to a major subclass of nucleotide-binding/leucine-rich repeat (NB-LRR) resistance (R) protein that has amino-terminal homology to the cytoplasmic domains of Drosophila and mammalian Toll and interleukin-1 family receptors (the so called 'TIR' domain). Similarities in the domain architecture of these proteins and animal regulators of programmed cell death have also been observed. Mutational screens revealed a number of genes that are required for RPP5-conditioned resistance. Among these are EDS1 and PAD4. Both EDS1 and PAD4 precede the function of salicylic acid-mediated plant responses. The EDS1 and PAD4 genes were cloned and found to encode proteins with similarity to the catalytic site of eukaryotic lipases, suggesting that they may function by hydrolysing a lipid-based substrate.

Stent attachment site-related endoleakage after stent graft treatment: An in vitro study of the effects of graft size, stent type, and atherosclerotic wall changes.

OBJECTIVE: Perigraft endoleakage is a major complication of the endovascular treatment of abdominal aortic aneurysms. The factors that cause this form of endoleakage are not completely identified. The effect of sizing of the prosthesis in combination with either self-expandable or balloon-expandable stents is evaluated in this study. Further, the influence of atherosclerotic changes on endoleakage is evaluated. METHODS: Eight human abdominal aortas were assessed macroscopically at 11 sites for the presence of atherosclerotic changes with intravascular ultrasound scanning (IVUS) and with computed tomography (CT). Five aortas were placed in in vitro circulation with physiologic parameters. After the determination of the proximal and distal landing site of the stent graft, the diameter and surface measurements of the cross sections were taken. The stent graft diameters were chosen from 4-mm undersizing to 6-mm oversizing, both for Gianturco stent grafts (William Cook Europe A/S, Bjaeverskov, Denmark) and for Palmaz stent grafts (Cordis/Johnson & Johnston Co, Warren, NJ). After placement of the stent graft, the diameter and surface measurements of the aortic cross section were determined at the proximal and distal stent attachment sites. The presence and size of the folds at the stent attachment site and the interface with the aortic wall were determined with IVUS and angioscopy. Endoleakage was evaluated with angiography. After angioplasty of the stent attachment site, IVUS, angioscopy, and angiography were repeated. RESULTS: Regarding atherosclerotic changes of the aortic wall, the correlations between clinical impression and CT, clinical impression and IVUS, and CT and IVUS were high (r = 0.77, r = 0.79 and r = 0.79, respectively). For the Gianturco stent grafts, no significant relationship existed between the diameters measured before and after stent graft placement, leading to great differences in intended and achieved oversizing. The achieved oversizing was less in the case of minimal atherosclerotic changes of the aortic wall. The Gianturco stent graft followed the aortic wall closely during the heart cycle. The sizes of the folds of the fabric were clearly correlated with the achieved oversizing (r = 0.83; P =.04) and the grade of endoleakage (r = 0.88; P =.022). Angioplasty after stent graft placement had no effect on the diameter and the grade of endoleakage. Palmaz stent grafts did not follow the aortic wall during the heart cycle. A significant correlation existed between oversizing and both space between aortic wall and stent graft (r = -0.88; P =.02) and grade of endoleakage (r = 0.84; P =.036). Grade of endoleakage in the Palmaz stent graft group was less than in the Gianturco stent graft group. CONCLUSION: With the use of Gianturco stents, a great difference between intended and achieved oversizing is accomplished. The atherosclerotic changes of the aortic wall possibly affect this finding. The configuration of the Gianturco stent results in the formation of fold in the case of oversizing, which is associated with endoleakage. However, the self-expandable character of the stent leads to a close relation to the aortic wall during the heart cycle, and this may possibly accommodate future aortic neck dilation. The Palmaz stent grafts do not follow the aortic wall during the heart cycle, but they do lead to better interface between the graft and the aortic wall, which results in less endoleakage.

An uncommon cause of stroke in young adults.

We describe a previously healthy 48-year-old man who presented with clinical characteristics suggestive of internal carotid artery dissection, confirmed by magnetic resonance imaging. He developed a massive infarction of the left cerebral hemisphere and died after 3 days of transtentorial herniation. Post-mortem examination identified a dissection of the thoracic aorta caused by Erdheim-Gsell cystic medionecrosis, with the characteristic degeneration of the elastic fibers of the lamina media. The dissection showed an unusually large extension not only distally into both iliac arteries, but also proximally into both carotid arteries. To our knowledge, such an extensive dissection has not been described previously. Underlying vessel wall disorders of the aorta, such as Erdheim Gsell cystic medionecrosis, should be considered in young patients with spontaneous arterial dissection.

Endoleak after stent-graft treatment of abdominal aortic aneurysm: a meta-analysis of clinical studies.

BACKGROUND: Endoleak is the major complication after endovascular treatment of abdominal aortic aneurysm (AAA) and its incidence seems to remain significant. Little is known about the association of device type and configuration with respect to the incidence, location, time of onset and fate of endoleakage. METHODS: A meta-analysis was performed via a Medline search of clinical studies after 1995 dealing with the endovascular treatment of AAA. Details of number of patients treated, configuration and type of endovascular device were collected. Data concerning site of origin, time of occurrence and fate of the endoleak were retrieved, along with information on change in diameter of the aneurysm with time. RESULTS: The 23 publications included reported on 1189 patients. The 1118 patients with successfully inserted transfemoral endovascular grafts experienced 270 endoleaks (24 per cent). The majority arose from the distal stent attachment site (36 per cent), were present immediately after stent-graft placement (66 per cent) and were persistent in time (37 per cent). Tube grafts were more frequently affected by endoleakage (35 per cent; P < 0.0001), especially at the distal stent attachment site (51 per cent), than bifurcated grafts (18 per cent; P = 0.004) and aortounilateral devices (20 per cent; P = 0.70). Self- expandable stent-grafts were more frequently associated with endoleaks (25 per cent) than balloon-expandable stent-grafts (17 per cent) (P = 0.037). CONCLUSION: Endovascular treatment of AAA is an evolving field. Even after the initial learning curve and attention to device-related problems, it is still accompanied by a significant number of endoleaks. Uniform presentation of results of treatment is necessary for analysing the effect of differences between patients, aneurysm morphology and device type.