REDUCTION OF MIGRAINES AFTER TREATMENT OF HEREDITARYHEMORRHAGIC TELANGIECTASIA (HHT)

Background: Pulmonary arteriovenous malformations (PAVMs) due to hereditaryhemorrhagic telangiectases (HHT) is associated with paradoxical strokes, brainabcesses, and increased prevalence of migraines. We report a patient in whom wefound a relationship between PAMVs and a reduction in frequency of migrainewith aura after the treatment of the first pulmonary malformation.Patient and methods: A 67-year-old woman developed migraine with visual auraand major epistaxis during childhood. A PAVM is discovered and surgically removedin 1969. Migraines nearly disappeared during several years, after which theystarted to reappear progressively. A HHT syndrome is diagnosed based on recurrentepistaxis, the development of cutaneous telangiectases and a positive family history.She suffered a left subcortical stroke in 2008. Perfusion CT, chest radiography,thoracic CT-angiography, contrast echocardiography, contrast transcranial Dopplerand cerebral MRI were performed.Results: Perfusion CT showed previous asymptomatic strokes in cerebellum andbasal ganglia. 4 PAMVs were confirmed on the chest x-ray whose structural conformationis identified on thoracic CT. Contrast echocardiography and transcranialDoppler showed a massive right to left shunt. It is planned to embolize the 4PAVMs, and migraine frequency will now be prospectively assessed.Conclusion: This patient with a pulmonary arteriovenous malformation showeda reduced migraine frequency after resection of her lung lesion. This suggests acausal relationship between a right to left shunt and migraine, as discussed inpatients with patent foramen ovale.

Cardiac CT: practical approach to integrate appropriate indications in daily practice.

Recent advances in CT technologies had significantly improved the clinical utility of cardiac CT. Major efforts have been made to optimize the image quality, standardize protocols and limit the radiation exposure. Rapid progress in post-processing tools dedicated not only to the coronary artery assessment but also to the cardiac cavities, valves and veins extended applications of cardiac CT. This potential might be however used optimally considering the current appropriate indications for use as well as the current technical imitations. Coronary artery disease and related ischemic cardiomyopathy remain the major applications of cardiac CT and at the same time the most complex one. Integration of a specific knowledge is mandatory for optimal use in this area for asymptomatic as for symptomatic patients, with a specific regards to patient with acute chest pain. This review aimed to propose a practical approach to implement appropriate indications in our routine practice. Emerging indications and future direction are also discussed. Adequate preparation of the patient, training of physicians, and the multidisciplinary interaction between actors are the key of successful implementation of cardiac CT in daily practice.

Severity of endoscopically detected esophageal inflammatory and fibrostenotic features correlates with degree of esophageal eosinophilia in adults with eosinophilic esophagitis

Background: Eosinophilic esophagitis (EoE) has emerged as a leading cause of dysphagia in adults. Characteristic esophageal features on endoscopy include structural/fibrostenotic (rings, narrow caliber, strictures) and inflammatory manifestations (longitudinal furrows, exudates, edema). Aim: The purpose of this study was to correlate the clinical, endoscopic and histopathologic features in adult EoE patients. Methods: A total of 106 encounters of 81 patients with EoE were analyzed. Data included an EoE-directed symptom-severity patient questionnaire evaluating symptoms of dysphagia (frequency, intensity, duration), meal duration, chest pain, and overall symptom severity. Video recordings of endoscopies were reviewed in a blinded manner using a classification and grading scheme for the esophageal features of EoE. Histopathology was reviewed for peak eosinophil count/high power field by pathologists blinded to the patients' clinical status. Associations between endoscopic features, histology and symptoms were evaluated using the Spearman rank correlation analysis. Results: The endoscopic severity of both structural and inflammatory esophageal features of EoE, including rings, exudates, longitudinal furrows, and edema, correlated significantly with peak eosinophil counts (see Table 1). Presence of "crepe paper mucosa" did not demonstrate significant association with peak eosinophil counts. Both structural (rings, narrow-caliber esophagus and strictures) and inflammatory (furrows, exudates and edema) composite endoscopic scores demonstrated a strong correlation with peak eosinophil counts. The strongest association with the degree of esophageal eosinophilia was found with a combination of both structural and inflammatory findings (p < 0.0001). The esophageal diameter (in mm) was negatively correlated with overall symptom severity (Spearman's rho = -0.4883, P = 0.0339). None of the individual or combined patient reported symptoms correlated significantly with either endoscopic or histopathologic findings. Conclusion: The severity of both structural and inflammatory endoscopic features associated with EoE is significantly associated with the degree of esophageal eosinophilia. Patient reported symptom severity was not associated with the degree of esophageal eosinophilia. Esophageal stricture diameter was inversely correlated with EoE symptom severity. The prognostic and therapeutic implications of these observations need to be determined.

Volemic status influences the response of plasma atrial natriuretic factor to positive airway pressure.

STUDY OBJECTIVE; To evaluate interactive effects of volemic status and positive end-expiratory pressure (PEEP) on the plasma levels of atrial natriuretic factor (ANF) in assist-controlled mechanical ventilation (MV). DESIGN: Three successive protocols applied in randomized order to each participant. SETTING: Clinical investigation laboratory. PARTICIPANTS: Twenty-one young, healthy adults. INTERVENTIONS: The three protocols were as follows: (1) MV+PEEP, normovolemia; (2) MV+PEEP, hypervolemia; and (3) spontaneous breathing (SB), hypervolemia. In protocols 1 and 2, a preliminary period of SB lasting 2 h was followed by MV alone (0.5 h), MV+20 cm H2O PEEP (1 h), and a recovery period of SB (1.5 h). Hypervolemia was induced by the continuous i.v. infusion of 3 L of 0.9% NaCl in 5 h (protocols 2 and 3). MEASUREMENTS AND RESULTS: Heart rate, BP, and the plasma levels of immunoreactive ANF and catecholamines were measured serially. During hypervolemia, ANF significantly decreased when PEEP was added to MV (protocol 2: from 31.1 +/- 2.7 to 20.7 +/- 1.5 fmol/mL; p < 0.01). This did not occur in normovolemia (protocol 1: from 20.0 +/- to 16.7 +/- 1.2 fmol/mL; p = NS). The different effects of MV+PEEP in normovolemia and hypervolemia were not related to differences in circulating catecholamine levels. CONCLUSIONS: These results demonstrate for the first time (to our knowledge) that volemic status modulates the response of plasma ANF to PEEP in humans. The role of ANF in the water and salt retention induced by MV with PEEP might be limited to hypervolemic conditions.

3-M syndrome associated with growth hormone deficiency: 18 year follow-up of a patient.

3-M syndrome is a rare autosomal recessive disorder that causes short stature, unusual facial features and skeletal abnormalities. Mutations in the CUL7, OBSL1 and CCDC8 genes could be responsible for 3-M syndrome.Here we describe the growth and evolution of dismorphic features of an Italian boy with 3-M syndrome and growth hormone deficiency (GHD) from birth until adulthood. He was born full term with a very low birth weight (2400 g=-3.36 standard deviation score, SDS) and length (40.0 cm =-6.53 SDS). At birth he presented with a broad, fleshy nose with anteverted nostrils, thick and patulous lips, a square chin, curvilinear shaped eyebrows without synophrys, short thorax and long slender bones. Then, during childhood tall vertebral bodies, hip dislocation, transverse chest groove, winged scapulae and hyperextensible joints became more evident and the diagnosis of 3-M syndrome was made; this was also confirmed by the finding of a homozygous deletion in exon 18 of the CUL7 gene, which has not been previously described.The patient also exhibited severe GHD (GH <5 ng/ml) and from the age of 18 months was treated with rhGH. Notwithstanding the early start of therapy and good compliance, his growth rate was always very low, except for the first two years of treatment and he achieved a final height of 132 cm (-6.42 SDS).

Symmetry-breaking in cumulative measures of shapes of polymer models.

Using numerical simulations we investigate shapes of random equilateral open and closed chains, one of the simplest models of freely fluctuating polymers in a solution. We are interested in the 3D density distribution of the modeled polymers where the polymers have been aligned with respect to their three principal axes of inertia. This type of approach was pioneered by Theodorou and Suter in 1985. While individual configurations of the modeled polymers are almost always nonsymmetric, the approach of Theodorou and Suter results in cumulative shapes that are highly symmetric. By taking advantage of asymmetries within the individual configurations, we modify the procedure of aligning independent configurations in a way that shows their asymmetry. This approach reveals, for example, that the 3D density distribution for linear polymers has a bean shape predicted theoretically by Kuhn. The symmetry-breaking approach reveals complementary information to the traditional, symmetrical, 3D density distributions originally introduced by Theodorou and Suter.

Dynamic responses of oxygen uptake at the onset and end of moderate and heavy exercise in trained subjects.

Inconsistencies about dynamic asymmetry between the on- and off-transient responses in VO2 are found in the literature. Therefore the purpose of this study was to examine VO2 on- and off-transients during moderate- and heavy-intensity cycling exercise in trained subjects. Ten men underwent an initial incremental test for the estimation of ventilatory threshold (VT) and, on different days, two bouts of square-wave exercise at moderate (<VT) and heavy (>VT) intensities. VO2 kinetics in exercise and recovery were better described by a single exponential model (<VT), or by a double exponential with two time delays (>VT). For moderate exercise, we found a symmetry of VO2 kinetics between the on- and off-transients (i.e., fundamental component), consistent with a system manifesting linear control dynamics. For heavy exercise, a slow component superimposed on the fundamental phase was expressed in both the exercise and recovery, with similar parameter estimates. But the on-transient values of the time constant were appreciably faster than the associated off-transient, and independent of the work rate imposed (<VT and >VT). Our results do not support a dynamically linear system model of VO2 during cycling exercise in the heavy-intensity domain.

Dynamic responses of O2 uptake at the onset and end of exercise in trained subjects.

Inconsistencies about dynamic asymmetry between the on- and off-transient responses in .VO2 are found in the literature. Therefore the purpose of this study was to examine .VO2on- and off-transients during moderate- and heavy-intensity cycling exercise in trained subjects. Ten men underwent an initial incremental test for the estimation of ventilatory threshold (VT) and, on different days, two bouts of square-wave exercise at moderate (<VT) and heavy (>VT) intensities. .VO2 kinetics in exercise and recovery were better described by a single exponential model (<VT) or by a double exponential with two time delays (>VT). For moderate exercise, we found a symmetry of .VO2 kinetics between the on- and off-transients (i.e., fundamental component), consistent with a system manifesting linear control dynamics. For heavy exercise, a slow component superimposed on the fundamental phase was expressed in both the exercise and recovery, with similar parameter estimates. But the on-transient values of the time constant were appreciably faster than the associated off-transient, and independent of the work rate imposed (<VT and >VT). Our results do not support a dynamically linear system model of .VO2 during cycling exercise in the heavy-intensity domain.

A CMR study of the effects of tissue edema and necrosis on left ventricular dyssynchrony in acute myocardial infarction: implications for cardiac resynchronization therapy.

ABSTRACT: BACKGROUND: In acute myocardial infarction (AMI), both tissue necrosis and edema are present and both might be implicated in the development of intraventricular dyssynchrony. However, their relative contribution to transient dyssynchrony is not known. Cardiovascular magnetic resonance (CMR) can detect necrosis and edema with high spatial resolution and it can quantify dyssynchrony by tagging techniques. METHODS: Patients with a first AMI underwent percutaneous coronary interventions (PCI) of the infarct-related artery within 24 h of onset of chest pain. Within 5-7 days after the event and at 4 months, CMR was performed. The CMR protocol included the evaluation of intraventricular dyssynchrony by applying a novel 3D-tagging sequence to the left ventricle (LV) yielding the CURE index (circumferential uniformity ratio estimate; 1 = complete synchrony). On T2-weighted images, edema was measured as high-signal (>2 SD above remote tissue) along the LV mid-myocardial circumference on 3 short-axis images (% of circumference corresponding to the area-at-risk). In analogy, on late-gadolinium enhancement (LGE) images, necrosis was quantified manually as percentage of LV mid-myocardial circumference on 3 short-axis images. Necrosis was also quantified on LGE images covering the entire LV (expressed as %LV mass). Finally, salvaged myocardium was calculated as the area-at-risk minus necrosis (expressed as % of LV circumference). RESULTS: After successful PCI (n = 22, 2 female, mean age: 57 ± 12y), peak troponin T was 20 ± 36ug/l and the LV ejection fraction on CMR was 41 ± 8%. Necrosis mass was 30 ± 10% and CURE was 0.91 ± 0.05. Edema was measured as 58 ± 14% of the LV circumference. In the acute phase, the extent of edema correlated with dyssynchrony (r2 = -0.63, p < 0.01), while extent of necrosis showed borderline correlation (r2 = -0.19, p = 0.05). PCI resulted in salvaged myocardium of 27 ± 14%. LV dyssynchrony (=CURE) decreased at 4 months from 0.91 ± 0.05 to 0.94 ± 0.03 (p < 0.004, paired t-test). At 4 months, edema was absent and scar %LV slightly shrunk to 23.7 ± 10.0% (p < 0.002 vs baseline). Regression of LV dyssynchrony during the 4 months follow-up period was predicted by both, the extent of edema and its necrosis component in the acute phase. CONCLUSIONS: In the acute phase of infarction, LV dyssynchrony is closely related to the extent of edema, while necrosis is a poor predictor of acute LV dyssynchrony. Conversely, regression of intraventricular LV dyssynchrony during infarct healing is predicted by the extent of necrosis in the acute phase.

Effects of brood manipulation costs on optimal sex allocation in social hymenoptera.

In eusocial Hymenoptera, queens and workers are in conflict over optimal sex allocation. Sex ratio theory, while generating predictions on the extent of this conflict under a wide range of conditions, has largely neglected the fact that worker control of investment almost certainly requires the manipulation of brood sex ratio. This manipulation is likely to incur costs, for example, if workers eliminate male larvae or rear more females as sexuals rather than workers. In this article, we present a model of sex ratio evolution under worker control that incorporates costs of brood manipulation. We assume cost to be a continuous, increasing function of the magnitude of sex ratio manipulation. We demonstrate that costs counterselect sex ratio biasing, which leads to less female-biased population sex ratios than expected on the basis of relatedness asymmetry. Furthermore, differently shaped cost functions lead to different equilibria of manipulation at the colony level. While linear and accelerating cost functions generate monomorphic equilibria, decelerating costs lead to a process of evolutionary branching and hence split sex ratios.

Kenny syndrome: evidence for idiopathic hypoparathyroidism in two patients and for abnormal parathyroid hormone in one.

We report three unrelated patients with Kenny syndrome. Clinical symptoms included severe dwarfism, with internal cortical thickening and medullary stenosis of the tubular bones, normal bone age, macrocephaly, absent diploic space, delayed closure of the anterior fontanel, and normal intelligence; two of the patients had hyperopia and papillary edema. The patients also had episodic hypocalcemic tetany and low serum levels of magnesium. In two patients the diagnosis of idiopathic hypoparathyroidism was established on the basis of undetectable serum parathyroid hormone (PTH) levels (N- and C-terminal RIAs); one of these had normal urinary cyclic adenosine monophosphate (cAMP) response to exogenous PTH. Circulating calcitonin was undetectable in either patient. In a third patient, who had abnormal body proportions, serum levels of PTH were increased in an RIA detecting predominantly intact PTH (N-RIA) and undetectable in another RIA recognizing carboxy-terminal fragments (C-RIA). Administration of PTH promptly increased urinary cAMP excretion. In this patient, serum levels of calcitonin were increased, whereas values for 25-OHD and 1,25(OH)2D were normal.

Morbidity, survival, and site of recurrence after mediastinal lymph-node dissection versus systematic sampling after complete resection for non-small cell lung cancer

BACKGROUND: Mediastinal lymph-node dissection was compared to systematic mediastinal lymph-node sampling in patients undergoing complete resection for non-small cell lung cancer with respect to morbidity, duration of chest tube drainage and hospitalization, survival, disease-free survival, and site of recurrence. METHODS: A consecutive series of one hundred patients with non-small-cell lung cancer, clinical stage T1-3 N0-1 after standardized staging, was divided into two groups of 50 patients each, according to the technique of intraoperative mediastinal lymph-node assessment (dissection versus sampling). Mediastinal lymph-node dissection consisted of removal of all lymphatic tissues within defined anatomic landmarks of stations 2-4 and 7-9 on the right side, and stations 4-9 on the left side according to the classification of the American Thoracic Society. Systematic mediastinal lymph-node sampling consisted of harvesting of one or more representative lymph nodes from stations 2-4 and 7-9 on the right side, and stations 4-9 on the left side. RESULTS: All patients had complete resection. A mean follow-up time of 89 months was achieved in 92 patients. The two groups of patients were comparable with respect to age, gender, performance status, tumor stage, histology, extent of lung resection, and follow-up time. No significant difference was found between both groups regarding the duration of chest tube drainage, hospitalization, and morbidity. However, dissection required a longer operation time than sampling (179 +/- 38 min versus 149 +/- 37 min, p < 0.001). There was no significant difference in overall survival between the two groups; however, patients with stage I disease had a significantly longer disease-free survival after dissection than after sampling (60.2 +/- 7 versus 44.8 +/- 8 months, p < 0.03). Local recurrence was significantly higher after sampling than after dissection in patients with stage I tumor (12.5% versus 45%, p = 0.02) and in patients with nodal tumor negative mediastinum (N0/N1 disease) (46% versus 13%, p = 0.004). CONCLUSION: Our results suggest that mediastinal lymph-node dissection may provide a longer disease-free survival in stage I non-small cell lung cancer and, most importantly, a better local tumor control than mediastinal lymph-node sampling after complete resection for N0/N1 disease without leading to increased morbidity.

Traitement des fibroses pulmonaires idiopathiques [Treatment of idiopathic pulmonary fibrosis]

Idiopathic pulmonary fibrosis still has to be diagnosed by elimination. Neoplasm, toxic treatments, collagen vascular disease, professional exposure or diagnosis such as sarcoidosis have to be ruled out. The repercussions on gas exchange are the most reliable indications of the severity of the disease, the pulmonary function test or chest x-rays alone being often misleading. Transbronchic biopsies, thoracotomy or thoracoscopies provide a precise diagnosis. In many cases only broncho-alveolar lavage and a high resolution CT-scan are performed to rule out infection or tumor and to assess the inflammatory state of the disease. Due to the often poor prognosis of this disease and its often poor response to steroids, the role of cytostatic drugs, cyclosporine and colchicine, and of pulmonary graft is discussed.

Randomized trial of pacemaker and lead system for safe scanning at 1.5 Tesla.

BACKGROUND: Magnetic resonance imaging (MRI) of pacemakers is a relative contraindication because of the risks to the patient from potentially hazardous interactions between the MRI and the pacemaker system. Chest scans (ie, cardiac magnetic resonance scans) are of particular importance and higher risk. The previously Food and Drug Administration-approved magnetic resonance conditional system includes positioning restrictions, limiting the powerful utility of MRI. OBJECTIVE: To confirm the safety and effectiveness of a pacemaker system designed for safe whole body MRI without MRI scan positioning restrictions. METHODS: Primary eligibility criteria included standard dual-chamber pacing indications. Patients (n = 263) were randomized in a 2:1 ratio to undergo 16 chest and head scans at 1.5 T between 9 and 12 weeks postimplant (n = 177) or to not undergo MRI (n = 86) post-implant. Evaluation of the pacemaker system occurred immediately before, during (monitoring), and after MRI, 1-week post-MRI, and 1-month post-MRI, and similarly for controls. Primary end points measured the MRI-related complication-free rate for safety and compared pacing capture threshold between MRI and control subjects for effectiveness. RESULTS: There were no MRI-related complications during or after MRI in subjects undergoing MRI (n = 148). Differences in pacing capture threshold values from pre-MRI to 1-month post-MRI were minimal and similar between the MRI and control groups. CONCLUSIONS: This randomized trial demonstrates that the Advisa MRI pulse generator and CapSureFix MRI 5086MRI lead system is safe and effective in the 1.5 T MRI environment without positioning restrictions for MRI scans or limitations of body parts scanned.

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Current applications of cardiac magnetic resonance (CMR) imaging offer a wide spectrum of indications in the setting of acute cardiac care. In particular, CMR is helpful for the differential diagnosis of chest pain by detection of myocarditis and pericarditis. Also, takotsubo cardiomyopathy and acute aortic diseases can be evaluated by CMR and are important differential diagnoses in patients with acute chest pain. In patients with restricted windows for echocardiography, CMR is the method of choice to evaluate complications of acute myocardial infarction (AMI). In AMI, CMR allows for a unique characterization of myocardial damage by quantifying necrosis, microvascular obstruction, oedema (=area at risk), and haemorrhage. These capabilities will help us to understand better the pathophysiological events during infarction and will also allow to assess new treatment strategies in AMI. To what extent the information on tissue damage will guide patient management is not yet clear and further research in this field is warranted. In the near future, CMR will certainly become more routine in acute cardiac care units, as manufacturers are now focusing strongly on this aspect of user-friendliness. Finally, in the next decade or so, MRI of other nuclei such as fluorine and carbon might become a clinical reality, which would allow for metabolic and targeted molecular imaging with excellent sensitivity and specificity