SMART syndrome: Classic transient symptoms leading to an unusual unfavorable outcome.

BACKGROUND: Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare complication of cerebral radiation therapy that usually presents>10 years after treatment as reversible paroxysmal episodes of neurological dysfunction associated with headaches. CASES: We report here on two cases of SMART syndrome in long-term survivors of high-grade glioma for whom neuropathological data were available. The course of the disease was unfavorable. Although the clinico-radiological picture of SMART syndrome clearly differs from classic cerebral radionecrosis, the gross neuropathological lesions observed in our two patients appeared to be similar to those described in focal radionecrosis. CONCLUSION: SMART syndrome may progress from a benign reversible form to a severe and eventually irreversible form. This severe course may also be confused with tumor progression, and lead to permanent disability and inadequate antitumor treatment. Clinicians should be aware of this latter atypical presentation.

Heart transplantation for Chagas cardiomyopathy in the United States.

Since an initial case in 2006, we noted multiple patients undergoing heart transplantation (HTx) for Chagas cardiomyopathy (CC) at our transplant program. The clinical characteristics, laboratory results and outcomes of patients with CC undergoing HTx in the United States have not been reported previously. In 2010, we implemented a systematic screening and management program for patients undergoing HTx for CC. Before HTx, all patients with idiopathic dilated cardiomyopathy who were born in a Chagas disease endemic country were screened for Trypanosoma cruzi (TC) infection with serology. After HTx, monitoring for TC reactivation was performed using clinical visits, echocardiography, endomyocardial biopsy and serial whole blood polymerase chain reaction (PCR) testing. Between June 2006 and January 2012, 11 patients underwent HTx for CC. One patient was empirically treated due to the presence of TC amastigotes in explanted cardiac tissue. Two patients experienced allograft dysfunction due to TC reactivation and three patients experienced subclinical reactivation (positive PCR results), which were treated. Chagas disease is a common cause of dilated cardiomyopathy in patients from endemic countries undergoing HTx at a transplant program in the United States. Reactivation is common after transplantation and can cause adverse outcomes.

[Medico-legal implications of infections during interventionnal cardiology procedure]. / Conséquences médico-légales des infections en cardiologie interventionnelle.

Nosocomial infections in interventional cardiology are rare, but their extreme severity is responsible for medico-legal issues. By the will of the legislator, it should be understood that, as soon as the nosocomial nature of an infection has been recognized, the victims will almost systematically obtain compensation. The payer will be determined by the level of seriousness of the infection and the existence or not of a possible fault. To avoid a conviction, the care teams must compel themselves to respect the recommendations of the professional societies, but also to ensure a perfect traceability of the prophylactic measures. Particular attention must be paid to the management of the vascular approach. Finally, it is essential to inform patients and all those involved in the healthcare chain of the need to get in touch with the intervention team if suspicious signs of an infection appear, to allow for specialized cares.

[Medico-legal issues of transcatheter aortic valve implantation (TAVI)]. / Implications médicolégales de l'implantation transcathéter de la valve aortique (TAVI).

Compassionally reserved for inoperable patients in 2002, Transcatheter Aortic Valve Implantation has now a place almost equivalent to surgical valve replacement. The pioneering teams first succeeded in demonstrating a benefit on the mortality of extremely serious patients, while managing a learning curve that seemed unreachable without a strong partnership with cardiac surgeons. This win/win challenge enabled cardiologists to surpass the limits they did not dare to brave (management of large arterial approach, annular rupture and tamponade) and surgeons to appropriate the endovascular's culture. The technological contribution, the maturity of the teams and the expansion to less severe populations have reduced the perioperative mortality of TAVI to less than 3%. At this stage, it seemed interesting to take stock of forensic developments around this technique. After a review of the studies and the healthcare requirements, we reported and analyzed the claims received from one of the leaders of the medical insurance in France. From this feedback, attempts will be made to identify ways of improving the prevention and subsequent treatment of complications, which will undoubtedly limit the risk of subsequent complaints.

Neural control of breathing: insights from genetic mouse models.

Recent studies described the in vivo ventilatory phenotype of mutant newborn mice with targeted deletions of genes involved in the organization and development of the respiratory-neuron network. Whole body flow barometric plethysmography is the noninvasive method of choice for studying unrestrained newborn mice. Breathing-pattern abnormalities with apneas occur in mutant newborn mice that lack genes involved in the development and modulation of rhythmogenesis. Studies of deficits in ventilatory responses to hypercapnia and/or hypoxia helped to identify genes involved in chemosensitivity to oxygen and carbon dioxide. Combined studies in mutant newborn mice and in humans have shed light on the pathogenesis of genetically determined respiratory-control abnormalities such as congenital central hypoventilation syndrome, Rett syndrome, and Prader-Willi syndrome. The development of mouse models has opened up the field of research into new treatments for respiratory-control disorders in humans.

[Medico-legal implications of coronary angioplasty among seniors]. / Quels risques médico-légaux en cardiologie interventionnelle chez les personnes âgées ?

It's commonplace to declare that seniors are more fragile, because of a higher rate of comorbidities and complex coronary lesions. However, they take great benefit from angioplasty during acute coronary syndrome, with a higher rate of complications. Based on the study of claims reported to a French medical insurer, it is found that people over 75 years old among victims of interventional cardiology accidents is proportional to the population of seniors in the French population (around 10%). Conversely, the mortality of those seniors was much higher than patients under 75 (83% versus 30%). A strategy, which involves families and anticipates the risks of those fragile patients (fragility of structures, risk of decompensation of comorbidities [kidneys, hemostasis]) can help to prevent the risk of accidents, but may also reduce medico-legal implications of cardiologists.

[Medical liability and coronary artery diseases]. / Responsabilité médicale et pathologie coronaire.

Until recently, for many people dying from a myocardial infarction was an inevitable fate. Myocardial infarction mortality rates have decreased drastically. At the same time, stents have clearly secured coronary angioplasties, removing the problems linked to coronary dissections such as abrupt closure or emergency coronary bypass. The iatrogenic risks have increased on account of the use of sophisticated techniques, powerful medications or the treatment of older patients. On the one hand, the media have informed people about the tremendous improvements in cardiology, however, on the other hand they have also given them over-optimistic expectations leading to an increase in the number of physicians sued. Now, physicians have to master ever more complex parameters such as new examination techniques prescriptions and interpretation (CT-scanner, MRI) and new medications. In order to prevent lawsuits, physicians should educate and inform their patients. To increase their chances in case of a lawsuit, physicians should improve the traceability of the treatment prescribed and information given to patients, but also make patients assume their responsibilities when they are reluctant to follow medical advices or treatments.

[Coronary artery disease and coronary angioplasty in chronic hemodialysis patients]. / Coronaropathie et angioplastie coronaire dans l'insuffisance rénale dialysée.

Chronic renal insufficiency leads to many cardiovascular complications and provide worst prognosis, especially when patients need hemodialysis. The atherosclerosis of chronic hemodialysis patients is qualified as "accelerated" by some authors, because of a very fast and large progression. To improve prognosis, it seems to be very important to detect and treat the frequent and serious underlying cardiovascular disease. Because of the high rate of diabetes mellitus, silent ischemia is a very frequent clinical situation. In the other hand, coronary artery disease in chronic hemodialysis patients is frequently complex, with a large coronary extension and high rate of coronary calcifications. Consequently, this disease needs a specific therapeutic approach. Even though, percutaneous coronary interventions (PCI) are more complex in this population, it provides good results, and improves patient's prognosis. However, the rate of complications of the vascular approach and the rate of restenosis is high. New devices, such as Drug Eluting Stents (DES) can critically decrease restenosis rate, and closure devices for trans-femoral approach, provides very encouraging results in this high risk population. Despite, good results of PCI with DES use, the mortality is still high in this population. To improve our efficiency, we have to progress in our therapeutic strategies and optimize medical approach to treat the important biological perturbations.

Patterns of relapse in patients with high grade glioma receiving combined treatments including stereotactic re-irradiation for a first relapse.

PURPOSE: Bevacizumab and stereotactic treatment are efficient combined or alone in relapse glioma. However, patterns of relapse after this kind of salvage treatment have never been studied. The purpose of this unicentric retrospective analysis was to assess and understand the patterns of relapse of high grade glioma treated with stereotactic radiation, with or without bevacizumab. PATIENTS AND METHODS: Twenty patients with high grade glioma relapse received a stereotactic radiation; among them two patients received temozolomide and eight patients received bevacizumab; among the latter, four received also irinotecan. We matched the stereotactic radiation treatment planning scan with the images of the first treatment and of the second relapse in order to determine the patterns of failure and associate dosimetric profile. RESULTS: For the total population, median follow-up from the first diagnosis and relapse were 46.1 and 17.6 months, respectively. Among the 13 patients who relapsed, ten did not receive chemotherapy and three received it (P<0.05), two received temozolomide and one bevacizumab. Patients who received bevacizumab had no "out-of-field" recurrences. Among the 32 irradiated relapses, 15 were "in-field" recurrences; among them two were treated with bevacizumab and 13 were not (P<0.05). For the 32 lesions, a favourable prognostic factor of control was the association of a high-dose of irradiation and the use of bevacizumab. CONCLUSION: For patients with relapsed high grade glioma, local control was higher with combined bevacizumab and high-dose stereotactic radiation.

Automatic classification of activity and apneas using whole body plethysmography in newborn mice.

An increasing number of studies in newborn mice are being performed to determine the mechanisms of sleep apnea, which is the hallmark of early breathing disorders. Whole body plethysmography is the method of choice, as it does not require immobilization, which affects behavioral states and breathing. However, activity inside the plethysmograph may disturb the respiratory signal. Visual classification of the respiratory signal into ventilatory activity, activity-related disturbances, or apneas is so time-consuming as to considerably hamper the phenotyping of large pup samples. We propose an automatic classification of activity based on respiratory disturbances and of apneas based on spectral analysis. This method was validated in newborn mice on the day of birth and on postnatal days 2, 5, and 10, under normoxic and hypoxic (5% O(2)) conditions. For both activity and apneas, visual and automatic scores showed high Pearson's correlation coefficients (0.92 and 0.98, respectively) and high intraclass correlation coefficients (0.96-0.99), supporting strong agreement between the two methods. The present results suggest that breathing disturbances may provide a valid indirect index of activity in freely moving newborn mice and that automatic apnea classification based on spectral analysis may be efficient in terms of precision and of time saved.

[Methacholine challenge in young children: measurement of resistance by interruption]. / Test a la métacholine chez le jeune enfant: Mesure de la résistance par interruption.

The aims of this study were 1. To evaluate the measurement of resistance by interruption (Rint) of bronchoconstriction induced by inhalation of methacholine and 2. To determine a threshold of increase of resistance in young children to differentiate responders from non-responders. Forty-six children (mean age 5 [4.3-6.1] years) referred for methacholine challenge were tested by measurement of Rint and transcutaneous oxygen tension. A fall of 20% or more in oxygen tension from the baseline was used to define the responders. The children studied had a baseline Rint significantly higher than normal (0.84 [0.68-1.01] vs. 0.76 [0.60-0.90] kPa L(-1)s; p < 0.03). Forty-one children were responders and had an increase in Rint significantly different from the non-responders (p < 0/04). An increase in Rint of 35% distinguished responders from non-responders in young children with chronic cough. Interrupter resistance increases significantly during bronchial provocation in responding young children and may be used to measure the degree of bronchoconstriction.

Successful Treatment of Mitochondrial Toxicity in an HIV-Positive Patient After Liver Transplantation.

Liver transplantation in patients infected with the human immunodeficiency virus (HIV) has been increasingly performed with reasonable outcomes; however, medical management of both immunosuppression and antiretroviral therapy can be challenging owing to drug toxicities and interactions. Nucleoside reverse transcriptase inhibitors (NRTIs), a common backbone of highly active antiretroviral therapy (HAART), were the first class of effective antiretroviral drugs developed. NRTIs are commonly used for posttransplant HAART therapy and have a rare but fatal complication of mitochondrial toxicity, manifesting as severe lactic acidosis, hepatic steatosis, and lipoatrophy. Herein, we have reported on the first known successful treatment of severe mitochondrial toxicity secondary to NRTIs in an HIV-infected transplant recipient.

MASH-1/RET pathway involvement in development of brain stem control of respiratory frequency in newborn mice.

Respiratory abnormalities have been described in MASH-1 (mammalian achaete-scute homologous gene) and c-RET ("rearranged during transfection") mutant newborn mice. However, the neural mechanisms underlying these abnormalities have not been studied. We tested the hypothesis that the MASH-1 mutation may impair c-RET expression in brain stem neurons involved in the control of breathing. To do this, we analyzed brain stem c-RET expression and respiratory phenotype in MASH-1 +/+ wild-type, MASH-1 +/- heterozygous, and MASH-1 -/- knock-out newborn mice during the first 2 h of life. In MASH-1 -/- newborns, c-RET gene expression was absent in the noradrenergic nuclei (A2, A5, A6, A7) that contribute to modulate respiratory frequency and in scattered cells of the rostral ventrolateral medulla. The c-RET transcript levels measured by quantitative RT-PCR were lower in MASH-1 -/- and MASH-1 +/- than in MASH-1 +/+ brain stems (P = 0.001 and P = 0.003, respectively). Breath durations were shorter in MASH-1 -/- and MASH-1 +/- than in MASH-1 +/+ mice (P = 0.022) and were weakly correlated with c-RET transcript levels (P = 0.032). Taken together, these results provide evidence that MASH-1 is upstream of c-RET in noradrenergic brain stem neurons important for respiratory rhythm modulation.

Fungal sinusitis in patients with AIDS: report of 4 cases and review of the literature.

We report here 3 cases of aspergillus sinusitis in patients with AIDS and the 1st fully described case, to our knowledge, of sinusitis associated with Pseudallescheria boydii in a patient with AIDS. We review the microbiology and pathology of fungal sinusitis in patients with AIDS and the morphologic and clinical features and treatment of P. boydii infection and aspergillus sinusitis. Fungal sinusitis in patients with HIV or AIDS generally occurs later in the course of primary disease with low CD4+ lymphocyte counts (< 50/mm3), unlike bacterial sinusitis which may occur at any time. Differentiation between invasive and noninvasive forms is likely not important, in contrast to fungal sinusitis in noncompromised patients. The number of cases is likely to increase as the number of patients with AIDS increases, patients survive longer, and other opportunistic infections are prevented or treated. Causative agents are likely to be resistant to fluconazole, which is in widespread use. Aspergillus sinusitis in patients with HIV or AIDS occurs in both those with and without traditional risk factors. Fungal sinusitis may present vexing management problems and be relentlessly progressive in the face of therapy. Ideal therapy has yet to be defined but an early combined surgical and medical approach in these compromised patients is preferred.

Vasoactive intestinal polypeptide microinjections into the oral pontine tegmentum enhance rapid eye movement sleep in the rat.

Rapid eye movement sleep can be elicited in the rat by microinjection of the cholinergic agonist carbachol into the oral pontine reticular nucleus. Intracerebroventricular administration, during the light period, of vasoactive intestinal peptide enhances rapid eye movement sleep in several species. Since this peptide is co-localized with acetylcholine in many neurons in the central nervous system, it was assumed that the oral pontine tegmentum could also be one target for vasoactive intestinal peptide to induce rapid eye movement sleep. This hypothesis was tested by recording the sleep-wakefulness cycle in freely-moving rats injected with vasoactive intestinal peptide or its fragments (1-12 and 10-28) directly into the oral pontine reticular nucleus. when administered into the posterior part of this nucleus, vasoactive intestinal peptide at 1 and 10 ng (in 0.1 microliter of saline), but not its fragments, induced a 2-fold enhancement of rapid eye movement sleep during 4 h, at the expense of wakefulness. At the dose of 10 ng, a significant increase in rapid eye movement sleep persisted for up to 8 h. Moreover, when the peptide was injected into the centre of the positive zone, rapid eye movement sleep was enhanced during three to eight consecutive days. These data provide the first evidence that rapid eye movement sleep can be elicited at both short- and long-term by a single intracerebral microinjection of vasoactive intestinal peptide. Peptidergic mechanisms, possibly in association with cholinergic mechanisms, within the caudal part of the oral pontine reticular nucleus may play a critical role in the long-term regulation of rapid eye movement sleep in rats.

Comparison of the prognostic value of C-reactive protein and troponin I in patients with unstable angina pectoris.

This study assessed the prognostic value of cardiac troponin I (cTnI) and C-reactive protein (CRP) in unstable angina, and specifically in patients with angiographically proven coronary artery disease. These biochemical parameters, which are related to myocardial injury or to systemic inflammation, may help in short-term risk stratification of unstable angina. We prospectively studied 195 patients with unstable angina, 100 of whom had angiographically proven coronary artery disease (with normal creatine kinase [CK] and CK-MB mass). Serum concentrations of cTnI (N < 0.4 ng/ml) and CRP (N < 3 mg/L) were measured at admission, 12, and 24 hours later. The rate of in-hospital major adverse cardiac events (death, myocardial infarction, or emergency revascularization) was higher in patients with increased cTnI within the first 24 hours, regardless of the results of coronary angiography (23% vs 7%; p < 0.001). Conversely, events occurred at similar rates in patients with or without increased CRP. In patients with angiographic evidence of coronary artery disease, multivariate analysis showed that increased cTnI within 24 hours of admission (35 patients) was an independent predictor of major adverse cardiac events (odds ratio 6.7, range 1.7 to 27.3), but not cTnI levels at admission and CRP at 0, 12, and 24 hours. Thus, both in unselected patients with unstable angina and in patients with angiographically proven coronary artery disease, increased cTnI within 24 hours of admission, but not CRP, is a predictor of in-hospital clinical outcome. We also found a temporal link between cTnI increase and late elevation of CRP, suggesting that systemic inflammation may partially be a consequence of myocardial injury.

Clinical and therapeutic aspects of obstructive sleep apnea syndrome in infants and children.

Sleep related increases in respiratory resistive loads in infants and children may or may not be associated with complete obstruction, i.e. obstructive apneas. Nevertheless, important clinical symptoms, both nocturnal and diurnal, may be present and should be taken into consideration. A thorough investigation must be performed to select the most appropriate therapy.

Development of the control of breathing: implications for sleep-related breathing disorders in infants.

Abnormal development of the control of breathing has implications for the occurrence and severity of SDB during infancy. Prevention of prenatal insults such as nicotine exposure should be included in public health programs. Infants at risk for SDB or with symptoms of SDB should be investigated for peripheral and central chemoreceptor dysfunction. Peripheral chemoreceptor function can be assessed using either the hyperoxic test or the alternating breath test, and central chemoreceptor function using the rebreathing test. Optimal treatment of SDB in the developing infant is of central importance for preserving normal behavior and neurocognitive development. Oxygen supplementation and/or ventilatory support during sleep prevent uncontrolled episodes of hypoxemia, sleep fragmentation, and REM sleep reduction. Finally, alterations in homeostatic responses during development may have long-term effects on breathing during sleep in childhood and adulthood. In genetically-predisposed subjects, environmental conditions during the period of development of respiratory control mechanisms may add to the intrinsic vulnerability to SDB.

Lung mechanics and breathing pattern during wakefulness and sleep in children with enlarged tonsils.

Thirteen children (mean age, 45 months) with nocturnal symptoms of upper airway obstruction, the result of enlarged tonsils, were tested during wakefulness (W) and sleep (S) induced by chloral hydrate (less than or equal to 50 mg/kg). During W, lung mechanics, blood gas, breathing pattern, and airflows during tidal breathing were in the normal range. During S, total lung resistance increased significantly, and dynamic lung compliance and transcutaneous PO2 decreased significantly. During S, the tidal volume (VT) and the mean inspiratory flow, normalized for body weight (BW), decreased whereas the ratio of the inspiratory time (TI) over the total duration of the respiratory cycle (TTOT) rose, indicating a longer contraction time of the respiratory muscles. The time to reach peak inspiratory flow, measured as a percentage of TI (dTI/TI), increased in seven children, with no change in the ratio of the expiratory flow over the inspiratory flow, both measured at 50% of VT (EF50/IF50). In three other patients dTI/TI decreased with an increase in EF50/IF50. We conclude that in children with enlarged tonsils, S modified lung mechanics, gas exchange, and the inspiratory components of the breathing pattern and airflow.

Resting lung function in children after repair of tetralogy of Fallot.

Children with tetralogy of Fallot had pulmonary function tests (PFT) after intracardiac repair (ICR). According to the age at time of ICR and to the existence or not of palliative surgery preceding ICR, they were divided into three groups. Group 1 had ICR at a mean of one year one month of age (range four months to one year seven months), that is, during the active period of postnatal lung growth. Groups 2 and 3 had ICR later in childhood, that is, respectively, at four years seven months (range two years nine months to 11 years 9 months) and at five years four months (range two years seven months to 11 years five months). In group 3, ICR was preceded by palliative surgery. The PFT at rest included measurement of lung volumes (functional residual capacity), vital capacity (VC), dynamic or static compliance (CL), total pulmonary resistance, lung transfer factor for CO (TLCO) and blood gases. Group 1 had normal lung function suggesting that early repair of TOF saves lung development. In groups 2 and 3, significant decrease in VC(p less than 0.01) and CL (p less than 0.01) were found suggesting impaired alveolar growth. Additional defect in TLCO (p less than 0.01) in group 3 suggested that palliative surgery induces abnormal vascular growth. Thus, the present functional results suggest repair of TOF during the two first years of life, ie, the active period of postnatal lung growth.