Multi-domain neurocognitive impairment following definitive intensity-modulated radiotherapy for nasopharyngeal cancer: A cross-sectional study.

INTRODUCTION: Neurocognitive impairment from inadvertent brain irradiation is common following intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). This study aimed to determine the prevalence, pattern, and radiation dose-toxicity relationship of this late complication. MATERIALS AND METHODS: We undertook a cross-sectional study of 190 post-IMRT NPC survivors. Neurocognitive function was screened using the Montreal Cognitive Assessment-Hong Kong (HK-MoCA). Detailed assessments of eight distinct neurocognitive domains were conducted: intellectual capacity (WAIS-IV), attention span (Digit Span and Visual Spatial Span), visual memory (Visual Reproduction Span), verbal memory (Auditory Verbal Learning Test), processing speed (Color Trail Test), executive function (Stroop Test), motor dexterity (Grooved Pegboard Test) and language ability (Verbal Fluency Test). The mean percentiles and Z-scores were compared with normative population data. Associations between radiation dose and brain substructures were explored using multivariable logistic regression. RESULTS: The median post-IMRT interval was 7.0 years. The prevalence of impaired HK-MoCA was 25.3 % (48/190). Among the participants, 151 (79.4 %) exhibited impairments in at least one neurocognitive domain. The predominantly impaired domains included verbal memory (short-term: mean Z-score, -0.56, p < 0.001; long-term: mean Z-score, -0.70, p < 0.001), processing speed (basic: mean Z-score, -1.04, p < 0.001; advanced: mean Z-score, -0.38, p < 0.001), executive function (mean Z-score, -1.90, p < 0.001), and motor dexterity (dominant hand: mean Z-score, -0.97, p < 0.001). Radiation dose to the whole brain, hippocampus, and temporal lobe was associated with impairments in executive function, verbal memory, processing speed, and motor dexterity. CONCLUSIONS: Neurocognitive impairment is prevalent and profound in post-IMRT NPC survivors. Cognitive assessment and rehabilitation should be considered part of survivorship care.

Virtual navigator automatic registration technology in abdominal application.

Real-time Ultrasound (US) image fusion with a pre-acquired second imaging dataset - Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and/or CT/PET - has become widely used in recent years for both diagnosis and image-guided interventional procedures. Liver and kidneys are the main focused anatomical districts, related to abdominal application. There are still nowadays some drawbacks, regarding the adoption of the fusion imaging technique in everyday practice especially regarding its ease of use and the time needed in order to obtain a precise real-time fusion between US and the second imaging modality. The present work is a preliminary study on the feasibility and practical use of an Automatic registration algorithm for CT-US real-time fusion imaging. Data obtained by tests performed on a Doppler phantom, for the assessment of the precision of the registration procedure and in-vivo Automatic registration tests, are presented.

Combined use of liquid chromatography with mass spectrometry and nuclear magnetic resonance for the identification of degradation compounds in an erythromycin formulation.

A commercial erythromycin formulation containing erythromycin A (EA) as the major compound showed the presence of an unknown degradation compound that was co-eluted with erythromycin E (EE) in the European Pharmacopoeia (Ph. Eur.) liquid chromatographic (LC) method. The amount of the degradation compound increased with respect to time. To separate this unknown (UNK1), investigation was performed with different LC methods coupled to ultraviolet detection (LC-UV). With the present Ph. Eur. method, the degradation compound could not be well separated. However, with the most selective LC-UV method (XTerra method), two more degradation products (UNK2 and UNK3) were found in the formulation which could not be observed using other methods because of their poor separation. By combining the results obtained with LC-UV, LC/MS and LC/NMR, the degradation products were identified as pseudoerythromycin A hemiketal (PsEAHK), erythromycin A enol ether carboxylic acid and erythromycin C enol ether carboxylic acid. PsEAHK is known to be a base-catalysed degradation product of EA, whereas the other two degradation products were newly identified.

Apolipoprotein E4 decreases whereas apolipoprotein E3 increases the level of secreted amyloid precursor protein after closed head injury.

Apolipoprotein E (apoE4) and head trauma are important genetic and environmental risk factors for Alzheimer's disease. Furthermore, apoE4 increases both the acute and chronic consequences of head trauma. The latter are associated with the deposition of amyloid-beta, which is particularly elevated in apoE4 subjects. The short-term effects of head injury are associated with transiently increased metabolism of amyloid precursor protein (APP) and its secreted fragment, APPs. In the present study, we examined the possibility that the acute, short-term pathological effects of apoE4 following head trauma and the corresponding neuroprotective effects of apoE3 are related to isoform-specific effects of apoE on APP metabolism. Accordingly, male transgenic mice expressing human apoE3 or apoE4 on a null mouse apoE background and apoE-deficient and control mice were subjected to closed head injury (CHI). The resulting effects on brain APP, and on its secreted products, APPs and secreted product of the alpha-cleavage of APP (APPsalpha) were then determined 24 h following injury. Immunoblotting revealed no significant differences between the basal APP, APPs and APPsalpha levels of the hippocampus or the cortex of the control and the apoE3 and ApoE4 transgenic mice. The apoE-deficient mice also had similar cortical basal levels of APP and its metabolites, whereas their corresponding basal hippocampal APP and APPs levels were lower than those of the other groups. CHI lowered the hipppocampal APPs and APPsalpha levels of the apoE4 transgenic mice, whereas those of the apoE3 transgenic mice and of the control and apoE-deficient mice were not affected by this insult. In contrast, CHI raised the cortical APP and APPs levels of the apoE3 transgenic mice but had no significant effect on those of the other mice groups. These animal model findings suggest that the acute, short-term pathological effects of apoE4 following CHI and the corresponding neuroprotective effects of apoE3 may be mediated by their opposing effects on the expression and cleavage of cortical and hippocampal APP. Similar isoform-specific interactions between apoE and APP may play a role in the acute, short-term effects of head trauma in humans.

Susceptibility of transgenic mice expressing human apolipoprotein E to closed head injury: the allele E3 is neuroprotective whereas E4 increases fatalities.

Apolipoprotein E, the major brain lipid-binding protein, is expressed in humans as three common isoforms (E2, E3 and E4). Previous studies revealed that the allele apolipoprotein E4 is a major genetic risk factor of Alzheimer's disease and that traumatic brain injury is associated with increased risk for developing this disease. Furthermore, it has been suggested that the effects of traumatic head injury and apolipoprotein E4 in Alzheimer's disease are synergistic. To test the hypothesis that the apolipoprotein E genotype affects susceptibility to brain injury, we subjected transgenic mice, expressing either human apolipoprotein E3 or human apolipoprotein E4 on a null mouse apolipoprotein E background and apolipoprotein E-deficient knockouts, to closed head injury and compared mortality, neurological recovery and the extent of brain damage of the survivors. More than 50% of the transgenic mice expressing human apolipoprotein E4 died following closed head injury, whereas only half as many of the transgenic mice expressing human apolipoprotein E3, and of the control and apolipoprotein E-deficient mice died during this period (P<0.02). A neurological severity score used for clinical assessment of the surviving mice up to 11 days after closed head injury revealed that the four mouse groups displayed similar severity of damage at 1h following injury. At three and 11 days post-injury, however, the neurological severity scores of the transgenic mice expressing human apolipoprotein E3 were significantly lower than those of the other three groups whose scores were similar, indicating better recovery of the transgenic mice expressing human apolipoprotein E3. Histopathological examination of the mice performed 11 days post-injury revealed, consistent with the above neurological results, that the size of the damaged brain area of the transgenic mice expressing human apolipoprotein E3 was smaller than that of the other head-injured groups. These findings show that transgenic mice expressing human apolipoprotein E4 are more susceptible than those expressing apolipoprotein E3 to closed head injury. We suggest that this effect is due to both a protective effect of apolipoprotein E3 and an apolipoprotein E4-related pathological function.

Patent foramen ovale and its embolic implications.

This study investigates the usefulness of the echocardiographic characteristics of patent foramen ovale (PFO) in the stratification of stroke recurrence risk in patients with acute ischemic cerebral disease. Shunting at rest and a highly mobile fossa ovalis membrane are more frequently detected in stroke patients with PFO as the only identifiable cause of embolism. For PFO patients with both rest patency and membrane mobility > 6.5 mm, the risk of stroke/transient ischemic attack recurrence was 7.6% (95% CI, 0-18.0) at 12 months and 12.5% (95% CI, 0-26.1) at 24 months (p = 0.05). The association of both rest patency and high membrane mobility seems to identify those stroke patients with PFO at higher risk for further brain embolism.

Increasing chronic subdural hematoma after endoscopic III ventriculostomy.

OBJECT: Endoscopic III ventriculostomy (ETV) is an effective and a rather safe treatment for noncommunicating hydrocephalus secondary to aqueductal stenosis and other obstructive pathologies. Though not devoid of risk, ETV is increasingly replacing shunt operations, and it prevents related complications, including overdrainage. METHODS: We report a rare case of a large chronic subdural hematoma (ChSDH) after ETV in a patient with aqueductal stenosis. Three weeks after he was shunted elsewhere, he presented to us with clinical symptoms of intracranial hypotension and overdrainage. ETV was performed and the shunt removed uneventfully. On routine postoperative MRI a few weeks later, a large ChSDH was noted, the patient being totally asymptomatic. Since the ChSDH grew significantly, causing a mass effect on the follow-up MRI, it was finally drained. Large and increasing ChSDHs have previously been reported secondary to overdrainage after shunt placement, but not after ETV. CONCLUSIONS: We conclude that though rare, a ChSDH may evolve even after ETV, if there is a substantial decrease in previously elevated intracranial pressure.

Diagnostic accuracy of transthoracic and multiplane transesophageal echocardiography for valvular perforation in acute infective endocarditis: correlation with anatomic findings.

We evaluated the diagnostic accuracy of transthoracic and multiplane transesophageal echocardiography (TTE and TEE, respectively) for assessing valvular perforation during active infective endocarditis by correlating the results of TTE and TEE with anatomic findings of 88 valves examined at surgery or autopsy. Compared with TEE, TTE has a low diagnostic sensitivity in the detection of this complication and, in the presence of hemodynamic instability, multiplane TEE should be performed directly.

Harmonic imaging with Levovist for transthoracic echocardiographic reconstruction of left ventricle in patients with post-ischemic left ventricular dysfunction and suboptimal acoustic windows.

BACKGROUND: Attempts to perform transthoracic 3-dimensional echocardiography (3DE) are often encumbered by poor definition of chamber borders in adult patients who have technically suboptimal acoustic windows. METHODS: To assess whether harmonic imaging (HI) and contrast agents can facilitate transthoracic 3DE assessment of the left ventricle, we used fundamental imaging (FI), HI alone, and HI coupled with the echo-enhancing contrast agent Levovist in 15 consecutive patients with post-ischemic left ventricular (LV) dysfunction and technically difficult windows. Dynamic 3DE image data sets were obtained at 5-degree angles (36 slices) from a transthoracic apical view. From these data a total of 240 myocardial segments were analyzed with the use of dynamic short-axis paraplane slices at basal, middle, and apical LV levels (standard 16 segment model). For border definition, each segment was scored in random sequence on the following scale by 2 independent investigators: 0 = not seen, 1 = suboptimal visualization, and 2 = well defined. RESULTS: Our results showed a significant increase in the number of well-visualized segments when harmonic mode combined with Levovist injection was compared with FI and HI alone. CONCLUSION: Harmonic imaging alone improves LV assessment by 3DE when compared with FI. Contrast imaging in which Levovist is added to HI further improves the capability of transthoracic tomographic 3DE in the visualization of LV myocardial segments. This could allow 3DE by transthoracic windows to be used more widely in adults for the evaluation of LV volume and function.

[D-lactic acidosis in short bowel syndrome].

A boy of 20 months and a girl of 27 months who had previously undergone massive bowel resection due to congenital intestinal obstruction are described. During gradual reduction of total parenteral nutrition and initiation of oral feeding, both developed severe, acute metabolic acidosis, accompanied by encephalopathy and ataxia. After the laboratory identification of massive amounts of the d-isomer of lactic acid in urine and blood, both were successfully treated with i.v. bicarbonate, and metronidazole to suppress the overgrowth of colonic lactobacilli responsible for the metabolic crisis.

Valvular perforation in left-sided infective endocarditis: a prospective echocardiographic evaluation and clinical outcome.

We undertook this study to determine the use of transthoracic and transesophageal echocardiography in detecting valvular perforation and the clinical impact of the latter on the outcome of left-sided infective endocarditis. Transthoracic echocardiography was performed in 58 consecutive patients with infective endocarditis. According to the study protocol, a subgroup of 42 patients also underwent transesophageal echocardiogrophy. At referral, 20 (34%) of 58 patients had echocardiographic evidence of valvular perforation (group A). No valvular perforations were found in the remaining 38 patients (group B). During a follow-up period of 27 +/- 16 months, a major complication occurred in 18 of 20 patients in group A and in 11 of 38 patients in group B (p < 0.0001). Univariate analysis indicated previous infective endocarditis, aortic involvement, and New York Heart Association functional class had a predictive value for valvular perforation (p < 0.001). Stepwise regression analysis confirmed aortic valve perforation as the only independent predictive variable for surgery and death. Valvular perforation is a common complication of infective endocarditis and is associated with an adverse outcome. Transthoracic echocardiography can detect or suggest valvular perforation in infective endocarditis, but transesophageal echocardiography better defines this complication and predicts severe heart failure or the need for early surgical management.

Role of transthoracic and transesophageal echocardiography in predicting embolic events in patients with active infective endocarditis involving native cardiac valves.

Some studies describe an increased risk for emboli in infective endocarditis patients with large (>10 mm) and mobile vegetations. Other studies fail to demonstrate the above relation. Most studies have been performed using transthoracic echocardiography or with a monoplane transesophageal approach. The present study examines whether distinctive characteristics of vegetative lesions detected by transthoracic and multiplane transesophageal echocardiography are predictive of embolic risk. We reviewed both transthoracic and transesophageal echocardiograms of 57 patients with diagnosis of acute infective endocarditis and no documented or suspected previous embolic events. We evaluated site, length, width, mobility, and echodensity of vegetations. Twenty-five patients (44%) had embolic events. No statistical differences in age, sex distribution, location of endocarditis, or offending pathogens between embolic (n = 25) and nonembolic (n = 32) patients were found. There were no differences in any of the echo characteristics of vegetations detected by transthoracic and transesophageal approach in embolic and nonembolic groups. Thus, transthoracic and transesophageal characteristics of vegetations are not helpful in defining embolic risk in patients with infective endocarditis.

Stethoscopes and otoscopes--a potential vector of infection?

OBJECTIVES: We aimed to determine whether stethoscopes and otoscopes used in community paediatric clinics harboured pathogenic micro-organisms, and, if so, which measures could prevent this. METHODS: Fifty-five stethoscopes belonging to paediatric physicians working in 12 community clinics were sampled for bacterial cultures by two methods: (i) direct impression of the diaphragm and bell section of each stethoscope for 5 seconds onto blood agar plates and a mannitol-salt-agar plate; (ii) swabbing the entire surface of the diaphragm of the stethoscope with a sterile cotton-tipped applicator. Forty-two otoscopes from the same physicians were sampled by rubbing the handles of the otoscopes with cotton-tipped swabs. The plates were incubated at 37 degrees C for 48 hours and examined for colony growth at 24 and 48 hours of incubation. Culture results were recorded as mean numbers of colony-forming units (CFUs). Eight additional stethoscope diaphragms were chosen at random at the participating clinics and cultured as described above. They were then wiped with alcohol swabs (isopropyl alcohol 70%), allowed to air dry for approximately 10 minutes and cultured a second time. RESULTS: All the stethoscopes and 90% of the otoscope handles were colonized by microorganisms. Staphylococci were isolated from 85.4% of the stethoscopes and 83.3% of the otoscopes, with 54.5% and 45.2% respectively being S. Aureus. Methicillin-resistant S. aureus were found in four each of the stethoscopes (7.3%) and otoscopes (9.5%). Cleaning with alcohol reduced the colony count by an average of 96.3%. CONCLUSIONS: Fomites can harbour potentially pathogenic bacteria, and with the increasing trend for children with more complex medical problems to be managed in an ambulatory setting, often by physicians who also work in hospitals, there is a real risk of spreading potentially serious infections to such patients. Simple cleansing with alcohol effectively eliminates the bacterial contamination of the fomites, and should be encouraged.

Effects of angiotensin-converting enzyme inhibition on left ventricular geometric patterns in patients with essential hypertension.

Although angiotensin-converting enzyme inhibitors have been shown to affect left ventricular (LV) remodeling favorably in several conditions, it remains unclear whether they can influence LV geometric pattern in hypertension. To address this issue, 122 patients (71 men and 51 women; mean age = 51 +/- 10 years) with mild to moderate hypertension were studied prospectively. All underwent clinical evaluation and Doppler echocardiography at entry and more than 2 years of quinapril therapy (10-40 mg/day). According to either LV mass (normal if < 131 g/m2 for men or < 100 g/m2 for women) or the ratio of LV posterior wall thickness to diastolic diameter (RWT; normal if < 0.45) at baseline, 58 patients had normal mass and RWT, 18 patients had concentric remodelling (i.e., normal mass but increased RWT), 24 patients had eccentric hypertrophy (i.e., increased mass but normal RWT), and 22 patients had concentric hypertrophy (i.e., increase in both mass and RWT). After 6 months of quinapril therapy, all patients with normal left ventricles showed the maintenance of mass and RWT within normal limits. Patients with concentric remodeling showed no increase in mass but had a significant decrease in RWT. Patients with eccentric hypertrophy exhibited a significant reduction in mass with no substantial change in RWT. Patients with concentric hypertrophy had a significant reduction in both mass and RWT. Changes in LV mass and geometry were maintained during the 2-year period of treatment and were paralleled by improvements in Doppler indices of LV diastolic function in each group. It is concluded that quinapril, with its well-known effects on LV hypertrophy, modifies the LV geometric pattern of hypertensive patients favorably, regardless of the presence of an abnormal LV mass or RWT.

[Planar determination of the aortic valve area with transesophageal echocardiography with multiplanar probe in patients with aortic stenosis and insufficiency. Comparison with transthoracic Doppler echocardiography]. / Determinazione planimetrica dell'area valvolare aortica mediante ecocardiografia transesofagea con sonda multiplana in soggetti con stenoinsufficienza aortica. Confronto con ecocardiografia Doppler transtoracica.

BACKGROUND: The simple determination of transaortic pressure gradient does not accurately assess the severity of an aortic valve stenosis. Thus, estimating the aortic valve area (AVA) is vital for clinical decision-making. Cardiac catheterization has been considered the "gold-standard" for the quantification of the stenotic valve area, but this technique may underestimate the actual valve area when aortic regurgitation is associated. Doppler transthoracic echocardiography (TTE) with the continuity equation method is usually employed for AVA estimation. Recently, in pure aortic stenosis, transesophageal echocardiography (TEE) has provided AVA values well-correlated to hemodynamic invasive results. METHODS: In this study, we correlated AVA values by TTE and multiplane TEE in 18 patients with combined aortic valve stenosis and regurgitation. RESULTS: The mean values of AVA by TEE and TTE were 0.74 +/- 0.12 and 0.68 +/- 0.55 cm2, respectively (p = NS). TEE-derived AVA correlated well to TTE-derived AVA (r = 0.816; p < 0.0001). Critical aortic stenosis was predicted by TEE with 100% sensitivity and specificity. Total time of examination was significantly longer for TTE (p < 0.00001). CONCLUSIONS: In conclusion, direct planimetry by multiplane TEE is a reliable method for AVA determination in aortic stenoinsufficiency. For this purpose, when the technical quality of TTE study is poor or when the patient is critically ill and does not tolerate a longer lasting TTE, multiplane TEE should be considered.

Noninvasive assessment of mitoxantrone cardiotoxicity in relapsing remitting multiple sclerosis.

Multiple sclerosis is the most common cause of neurologic disability in young adults. Recent reports have suggested that Mitoxantrone might be a candidate for clinical trials in multiple sclerosis patients. The authors studied 20 patients with relapsing remitting multiple sclerosis to evaluate cardiac toxicity during a one-year follow-up period. Patients were divided into 2 groups: group A, mitoxantrone treated patients (cumulative dose of 96 mg/m2); group B, placebo patients. The clinical course of multiple sclerosis was assessed using the Expanded Disability Status Scale and the number of relapses during the follow-up. Each patient had an electrocardiogram and a spectral and color flow Doppler echocardiographic examination at enrollment, and 6 and 12 months later, to investigate cardiac toxicity. The mean exacerbation rate was reduced significantly in group A patients. No significant differences in the electrocardiograms or the echocardiographic parameters of systolic and diastolic function were noted between the two groups or in group A during the follow-up. Mitoxantrone treatment seems able to improve the clinical course of relapsing remitting multiple sclerosis patients. It does not show any cardiac toxicity in selected patients at this dosage.

Continuous monitoring by biplane transesophageal echocardiography of pulmonary and paradoxical embolism.

Paradoxical embolism is considered a relatively uncommon disease. Continuous biplane transesophageal echocardiography (TEE) was performed in a 64-year-old woman who had an acute pulmonary embolism. TEE showed an elongated formation highly mobile within both atria. It was trapped in the interatrial septum, passing through a patent foramen ovale. Systemic embolism of the right arm was noted. The patient died 5 hours after admission, and postmortem examination confirmed the diagnosis of pulmonary embolism. This case demonstrates the potential utility of TEE in the study of patients with suspected paradoxical embolism.