SPECT/CT imaging of inflammation and calcification in human carotid atherosclerosis to identify the plaque at risk of rupture.

BACKGROUND: Calcification and inflammation are atherosclerotic plaque compositional biomarkers that have both been linked to stroke risk. The aim of this study was to evaluate their co-existing prevalence in human carotid plaques with respect to plaque phenotype to determine the value of hybrid imaging for the detection of these biomarkers. METHODS: Human carotid plaque segments, obtained from endarterectomy, were incubated in [111In]In-DOTA-butylamino-NorBIRT ([111In]In-Danbirt), targeting Leukocyte Function-associated Antigen-1 (LFA-1) on leukocytes. By performing SPECT/CT, both inflammation from DANBIRT uptake and calcification from CT imaging were assessed. Plaque phenotype was classified using histology. RESULTS: On a total plaque level, comparable levels of calcification volume existed with different degrees of inflammation and vice versa. On a segment level, an inverse relationship between calcification volume and inflammation was evident in highly calcified segments, which classify as fibrocalcific, stable plaque segments. In contrast, segments with little or no calcification presented with a moderate to high degree of inflammation, often coinciding with the more dangerous fibrous cap atheroma phenotype. CONCLUSION: Calcification imaging alone can only accurately identify highly calcified, stable, fibrocalcific plaques. To identify high-risk plaques, with little or no calcification, hybrid imaging of calcification and inflammation could provide diagnostic benefit.

Perspectives on Small Animal Radionuclide Imaging; Considerations and Advances in Atherosclerosis.

This review addresses nuclear SPECT and PET imaging in small animals in relation to the atherosclerotic disease process, one of our research topics of interest. Imaging of atherosclerosis in small animal models is challenging, as it operates at the limits of current imaging possibilities regarding sensitivity, and spatial resolution. Several topics are discussed, including technical considerations that apply to image acquisition, reconstruction, and analysis. Moreover, molecules developed for or applied in these small animal nuclear imaging studies are listed, including target-directed molecules, useful for imaging organs or tissues that have elevated expression of the target compared to other tissues, and molecules that serve as substrates for metabolic processes. Differences between animal models and human pathophysiology that should be taken into account during translation from animal to patient as well as differences in tracer behavior in animal vs. man are also described. Finally, we give a future outlook on small animal radionuclide imaging in atherosclerosis, followed by recommendations. The challenges and solutions described might be applicable to other research fields of health and disease as well.

Alliance and Treatment Outcome in Family-Involved Treatment for Youth Problems: A Three-Level Meta-analysis.

Alliance has been shown to predict treatment outcome in family-involved treatment for youth problems in several studies. However, meta-analytic research on alliance in family-involved treatment is scarce, and to date, no meta-analytic study on the alliance-outcome association in this field has paid attention to moderating variables. We included 28 studies reporting on the alliance-outcome association in 21 independent study samples of families receiving family-involved treatment for youth problems (N = 2126 families, M age youth ranging from 10.6 to 16.1). We performed three multilevel meta-analyses of the associations between three types of alliance processes and treatment outcome, and of several moderator variables. The quality of the alliance was significantly associated with treatment outcome (r = .183, p < .001). Correlations were significantly stronger when alliance scores of different measurement moments were averaged or added, when families were help-seeking rather than receiving mandated care and when studies included younger children. The correlation between alliance improvement and treatment outcome just failed to reached significance (r = .281, p = .067), and no significant correlation was found between split alliances and treatment outcome (r = .106, p = .343). However, the number of included studies reporting on alliance change scores or split alliances was small. Our findings demonstrate that alliance plays a small but significant role in the effectiveness of family-involved treatment. Future research should focus on investigating the more complex systemic aspects of alliance to gain fuller understanding of the dynamic role of alliance in working with families.

Safety and long-term effects of renal denervation: Rationale and design of the Dutch registry.

BACKGROUND: Percutaneous renal denervation (RDN) has recently been introduced as a treatment for therapy-resistant hypertension. Also, it has been suggested that RDN may be beneficial for other conditions characterised by increased sympathetic nerve activity. There are still many uncertainties with regard to efficacy, safety, predictors for success and long-term effects. To answer these important questions, we initiated a Dutch RDN registry aiming to collect data from all RDN procedures performed in the Netherlands. METHODS: The Dutch RDN registry is an ongoing investigator-initiated, prospective, multicentre cohort study. Twenty-six Dutch hospitals agreed to participate in this registry. All patients who undergo RDN, regardless of the clinical indication or device that is used, will be included. Data are currently being collected on eligibility and screening, treatment and follow-up. RESULTS: Procedures have been performed since August 2010. At present, data from 306 patients have been entered into the database. The main indication for RDN was hypertension (n = 302, 99%). Patients had a mean office blood pressure of 177/100 (±29/16) mmHg with a median use of three (range 0-8) blood pressure lowering drugs. Mean 24-hour blood pressure before RDN was 157/93 (±18/13) mmHg. RDN was performed with different devices, with the Simplicity™ catheter currently used most frequently. CONCLUSION: Here we report on the rationale and design of the Dutch RDN registry. Enrolment in this investigator-initiated study is ongoing. We present baseline characteristics of the first 306 participants.

Percutaneous coronary intervention without on site surgical back-up; two-years registry of a large Dutch community hospital.

AIMS: To assess safety and efficacy of off-site percutaneous coronary intervention (PCI) in The Dutch invasive cardiovascular system. METHODS AND RESULTS: Descriptive single centre registry of elective and emergency PCI. Setting is a Dutch community hospital, 40 km north of Amsterdam, with an adherent population of 400,000 people. A Clinical follow up of Major Adverse Cardiac and Cerebral Events (MACCE) at 30 days post PCI is performed. The total number of participants eligible for PCI was 781 of whom 545 were men and 236 women. During a two-year period 781 PCI's were performed of which 298 were emergency and 483 elective. Acute complications occurred in 2.1% of participants. MACCE-free was 86.9% in the group with AMI and 95.8% in the elective group. CONCLUSIONS: Off-site PCI is feasible and safe in The Netherlands on the condition that specific key factors for success are taken into consideration.

Diagnosing diastolic heart failure.

BACKGROUND: increasing evidence supports the existence of left ventricular diastolic dysfunction as an important cause of congestive heart failure, present in up to 40% of heart failure patients. AIM: to review the pathophysiology of LV diastolic dysfunction and diastolic heart failure and the currently available methods to diagnose these disorders. RESULTS: for diagnosing LV diastolic dysfunction, invasive hemodynamic measurements are the gold standard. Additional exercise testing with assessment of LV volumes and pressures may be of help in detecting exercise-induced elevation of filling pressures because of diastolic dysfunction. However, echocardiography is obtained more easily, and will remain the most often used method for diagnosing diastolic heart failure in the coming years. MRI may provide noninvasive determination of LV three-dimensional motion during diastole, but data on correlation of MRI data with clinical findings are scant, and possibilities for widespread application are limited at this moment. CONCLUSIONS: in the forthcoming years, optimal diagnostic and therapeutic strategies for patients with primary diastolic heart failure have to be developed. Therefore, future heart failure trials should incorporate patients with diastolic heart failure, describing precise details of LV systolic and diastolic function in their study populations.

Comparison of iodine-123 epidepride and iodine-123 IBZM for dopamine D2 receptor imaging in clinically non-functioning pituitary macroadenomas and macroprolactinomas.

UNLABELLED: We compared pituitary iodine-123 epide- pride single-photon emission tomography (SPET) and 123I-IBZM SPET for the in vivo imaging of dopamine D2 receptors in 15 patients with clinically non-functioning pituitary adenomas. Four patients with dopamine agonist-sensitive macroprolactinomas were studied as positive controls. The uptake of radioactivity in the pituitary was established using a visual scoring system and an uptake index calculated by dividing the average count rates in the pituitary area by the average count rates in the cerebellum. All four macroprolactinomas showed specific binding of 123I-epidepride, but only one showed specific binding of 123I-IBZM. Specific binding of 123I-epidepride was demonstrated in 9 of the 15 clinically non-functioning pituitary adenomas (60%), but specific binding of 123I-IBZM was shown in only 6 of these 15 cases (40%). The uptake of 123I-epidepride in the pituitary region was consistently higher than that of 123I-IBZM. None of the patients who showed absence of uptake of 123I-epidepride in the pituitary area showed uptake of 123I-IBZM in this area. IN CONCLUSION: 123I-epidepride SPET is superior to 123I-IBZM SPET for the visualization of dopamine receptor-positive pituitary adenomas. Therefore, 123I-epidepride should replace 123I-IBZM for future D2 receptor SPET studies of pituitary adenomas. 123I-epidepride SPET potentially might serve to predict the response of clinically non-functioning pituitary adenomas to dopamine agonist therapy.

Complications after intracoronary stent implantation: three cases.

Complications after implantation of articulated Palmaz-Schatz stents in coronary arteries of 3 patients are reported. In 1 patient, embolization of the stent occurred during the acute phase, and in the other 2 patients, we observed restenosis after 4 and 5 months, respectively. Late restenosis was located in the midportion and the distal end of the stent in 1 patient. In the other patient a severe subtotal occlusion was found 1 cm proximal to the stent. These findings suggest that adaptation of the stent delivery system is needed to prevent loss of the stent and scraping of the vessel wall.

Clinical characteristics and coronary angiographic findings of patients with unstable angina, acute myocardial infarction, and survivors of sudden ischemic death occurring during and after sport.

The clinical characteristics and coronary angiographic findings of 42 well-conditioned subjects with an acute ischemic event related to sport are reported. Five patients had unstable angina, 25 had acute myocardial infarction (AMI), and 12 were resuscitated victims of sudden ischemic death. Twenty-two events occurred during sport (group A) and 20 after sport (group B). There were two women and 40 men. The mean age was 46 years (range 25 to 65). Twelve out of 30 patients who smoked cigarettes had an adjunctive risk factor for coronary artery disease. Twelve others (28%) had no identifiable risk factor. Prodromal cardiac symptoms were detected in three patients (group A). Two patients had previous myocardial infarction (group B). Coronary angiography was performed acutely in 39 patients. The distribution of the ischemia-related coronary artery was comparable in both groups. The lesion morphology of 35 culprit coronary arteries was described as concentric in six patients and eccentric with regular borders (type I lesion) in 11 and irregular borders (type II lesion) in 18. Eccentric lesions consistent with ruptured plaques prevailed in both groups. Associated coronary artery disease was present in 10 patients. There was no relationship between the number of risk factors and the extent of diseased coronary arteries. Clinical characteristics and coronary angiographic findings of patients with unstable angina, AMI, and sudden death either during or after sport are similar and indicate a common pathogenesis. The probable mechanism of a coronary event related to sport is exercise-induced plaque rupture. In most instances such an event is unexpected and unpredictable. Identification of some subjects at risk is possible.

[Cardiomyoplasty: a new alternative in chronic heart failure]. / Het wikkelhart: een nieuw alternatief bij chronisch hartfalen.

The technique of cardiomyoplasty to support the failing heart as applied in the first two patients in The Netherlands is reported. Indications are presented for the selection of patients who might benefit from a cardiomyoplasty procedure, considering its experimental nature.

Hyperventilation and panic attacks.

The symptoms of hyperventilation syndrome and panic disorder are very similar. A questionnaire was used to assess the incidence of panic disorder in 274 patients; 35% of the patients with hyperventilation and only 5% of the non-hyperventilating patients showed panic disorder. The authors conclude that hyperventilation plays an important role in panic disorder and in generalized anxiety disorder.

A new technique for angioplasty of occluded coronary arteries and bypass grafts, not associated with acute myocardial infarction.

We describe a new technique for angioplasty of totally occluded coronary arteries and bypass grafts in the absence of acute myocardial infarction. We used a guiding catheter, a coronary infusion catheter, and a relatively stiff steerable guide wire to perforate the occlusion. Angioplasty of the recanalized vessel was subsequently performed. The procedure was attempted in nine patients; it was successful in eight. There were no complications. The advantages of this technique are discussed.

Systemic effects of anisoylated plasminogen streptokinase activator complex and streptokinase therapy in acute myocardial infarction. Coagulation aspects of the Dutch Invasive Reperfusion Study.

The systemic effects of intravenous anisoylated plasminogen streptokinase activator complex (APSAC; 30U) and intracoronary streptokinase (250,000U) were compared in 54 patients with acute myocardial infarction. In 3 patients, no signs of a systemic lytic state were observed. In all other patients, significant reductions of coagulation and fibrinolytic factors occurred: fibrinogen levels decreased by 86% in the APSAC group and 81% in the streptokinase group; for plasminogen the decreases were 68 and 66%, and for alpha 2-antiplasmin activity greater than 95 and 94%, respectively. Fibrin(ogen) degradation products were increased 68- and 38-fold, respectively. Although there was a trend for the lytic state to be more profound in the APSAC-treated patients, there was no difference between treatment groups with regard to bleeding complications or therapeutic efficacy, the latter being 79 and 73%, respectively, for APSAC and streptokinase. Total fibrinolytic activity, measured as euglobulin clot lysis time, was sustained for longer in the APSAC group, which may explain the low reocclusion rate in this group in comparison with the streptokinase group.

The effects of nicotinic acid and xanthinol nicotinate on human memory in different categories of age. A double blind study.

The treatment effect of nicotinic acid and xanthinol nicotinate on human memory was compared with placebo in 96 healthy subjects. Forty-three subjects were young (35-45 years), 30 subjects middle aged (55-65 years) and 23 subjects were old aged (75-85 years). Pre- and post-treatment scores were measured on a battery of memory tasks, covering sensory register, short-term memory and long-term memory. The treatment regime was 1 dragee t.i.d. for 8 weeks. The administration of xanthinol nicotinate (500 mg, containing 141.7 mg nicotinic acid), nicotinic acid (141.7 mg) and placebo (lactose) was double-blind. Pre- and post-treatment scores were analysed by means of a multivariate covariance technique, the pre-treatment score serving as covariate. Nicotinic acid treatment resulted in improvement of sensory register and short-term memory, while xanthinol nicotinate improved sensory register, short-term memory and long-term memory. In comparison with placebo, both active compounds yielded improvements of 10-40%, depending on type of task. Treatment effects of nicotinic acid were predominantly found in the young and middle-aged, whereas treatment effects of xanthinol nicotinate were predominantly found in the old. These results are interpreted by the supposed activity of nicotinic acid at the cell membrane, improving neuronal transmission, and of xanthinol nicotinate inside the cell, enhancing cell metabolism and oxygen supply in the brain.

A controlled study of a breathing therapy for treatment of hyperventilation syndrome.

A therapy directed toward slowing and regularizing the ventilatory pattern was compared with a partial-treatment, comparison procedure for individuals with somatic and psychological symptoms attributable to hyperventilation episodes (i.e. hyperventilation syndrome). Comparing repeated measures between a pretreatment baseline session and a post-treatment followup, we found that the experimental therapy, in contrast to the comparison procedure, produced a greater number of, and more extensive, improvements in psychological, symptom complaint and ventilatory dimensions. Results also suggest changes in central respiratory control mechanisms as a consequence of treatment.

Abomasal emptying in sheep as related to the amount of protein entering the abomasum.

In sheep, provided with re-entrant cannulas in the caudal duodenum and with an infusion tube into the abomasal fundus, emptying of the liquid phase of the abomasal contents was studied with [57Co]EDTA. Radioactivity was measured continuously with Geiger-Müller counters placed along the re-entrant cannulas. It appeared that first-order kinetics could be applied to the elimination of [57Co]EDTA from the abomasum. Mean retention time of this label in the abomasum was 40-50 min. Infusion of a suspension of soya-bean protein in saline (9 g sodium chloride/l) caused an initially decreased rate of abomasal emptying, but after 48 h an adaptation had occurred to the original rate of emptying producing an increased volume of abomasal contents and increased flow-rate of digesta into the duodenum.

Diagnosis of hyperventilation syndrome on the basis of reported complaints.

Four hundred consecutive patients referred for diagnosis of hyperventilation syndrome were studied to assess the utility of self-reported complaints for making primary diagnoses of the syndrome. One-half of the subjects were unequivocally diagnosed as positive for the disorder, the other half as negative. This diagnosis was determined by the presence or absence of two criteria with established validity: (a) recognition of major presenting symptoms during a period of voluntary hyperventilation, and (b) slow return of end-tidal CO2 levels to pre-hyperventilation baseline values after the voluntary period of overbreathing. Analyses focused on differences in presenting symptoms between those patients with and those without the syndrome. Results revealed many significant differences in frequency of specific complaints between groups. However, there was much overlap between groups with regard to all complaints. A discriminant analysis of the complaint items led to a correct classification of 66 per cent of the subjects. Our findings thus indicate that the risks of misclassification of hyperventilation syndrome are relatively large when diagnosis is solely based on presenting complaints. Consequently, reported symptoms characteristic of the disorder should be used as preliminary indications requiring further evaluation.