Evaluation of cerebrospinal fluid alpha-synuclein seed amplification assay in PSP and CBS.

Background: Seed amplification assay (SAA) testing has become an important biomarker in the diagnosis of alpha-synuclein related neurodegenerative disorders. Objectives: To assess the rate of alpha-synuclein SAA positivity in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), and analyse the clinical and pathological features of SAA positive and negative cases. Methods: 106 CSF samples from clinically diagnosed PSP (n=59), CBS (n=37) and indeterminate parkinsonism cases (n=10) were analysed using alpha-synuclein SAA. Results: Three cases (1 PSP, 2 CBS) were Multiple System Atrophy (MSA)-type SAA positive. 5/59 (8.5%) PSP cases were Parkinson's disease (PD)-type SAA positive, and these cases were older and had a shorter disease duration compared with SAA negative cases. In contrast, 9/35 (25.7%) CBS cases were PD-type SAA positive. Conclusions: Our results suggest that PD-type seeds can be detected in PSP and CBS using a CSF alpha-synuclein SAA, and in PSP this may impact on clinical course.

Prediction of behavioural and cognitive deficits in patients with traumatic brain injury at an acute rehabilitation setting.

OBJECTIVE: The goal of this study was to identify factors that would predict short-term neuropsychological outcome in patients with traumatic brain injury (TBI) hospitalized in an acute rehabilitation setting. METHODS: Data was collected in the context of an acute early rehabilitation setting of a trauma centre. A brief neuropsychological assessment was carried out for 348 patients within a month following their trauma. RESULTS: Length of post-traumatic amnesia (PTA) was the best predictor of behavioural, memory and executive function variables within a month post TBI. The odds of being agitated, labile, irritable and disinhibited at one month post trauma were almost six times higher for those with PTA that lasted more than 7 days compared to those with a PTA of less than 24 hours. Also, the odds of having a higher mental manipulation score (less significant executive function impairment) were almost two times lower for those with frontal lesions, and three to six times lower for those with PTA of more than 24 hours. In addition, TBI severity, education and age were considered good predictors of some aspects of neuropsychological outcome. CONCLUSION: This model may help clinicians and administrators recognize the probable post-traumatic deficits as quickly as possible and to plan interventions as well as post-acute discharge orientation accordingly and early on.

Olfactory function in acute traumatic brain injury.

OBJECTIVE: Traumatic brain injury (TBI) represents a significant public health problem and is associated with a high rate of mortality and morbidity. Although TBI is amongst the most common causes of olfactory dysfunction the relationship between injury severity and olfactory problems has not yet been investigated with validated and standardized methods in the first days following the TBI. METHODS: We measured olfactory function in 63 patients admitted with TBI within the first 12 days following the trauma by means of the Sniffin' Sticks identification test (quantitative assessment) and a parosmia questionnaire (qualitative assessment). TBI severity was determined by means of the Glasgow Coma Scale (GCS) and by duration of post-traumatic amnesia (PTA) as measured by the Galveston Orientation and Amnesia Test. RESULTS: Poor olfactory scores correlated with a longer amnesia period, but not with GCS scores. Further, we observed higher parosmia scores in assault victims than in victims of falls or motor vehicle collisions. CONCLUSIONS: We show that PTA is intimately related to olfactory problems following a TBI. Thus, a thorough evaluation of olfaction is essential in order to detect posttraumatic olfactory dysfunction and to take appropriate actions early on to help the individual deal with this impairment.

Olfactory and executive dysfunctions following orbito-basal lesions in traumatic brain injury.

OBJECTIVE: To study the acute relationship between olfactory function and traumatic brain injury (TBI), cognitive functions and outcome. METHODS: Sixty-two patients with TBI were evaluated within the first 2 weeks following TBI. The Sniffin'Sticks identification test was used to assess olfaction. A neuropsychological evaluation was carried out to assess attention, verbal fluency, naming, memory, problem-solving and mental flexibility. The extended Glasgow Outcome Scale (GOSE) and the Disability Rating Scale (DRS) were rated at discharge from acute care. RESULTS: Traumatic lesions located in the basal frontal area resulted in odour identification scores that were significantly lower than when lesions were elsewhere (p < 0.001). A significant positive correlation was shown between odour identification scores and mental flexibility scores (p = 0.004) and patients with hyposmia had worse performances on executive tests measuring problem-solving, verbal fluency and mental flexibility (p < 0.01). Moreover, the odour identification score and the DRS total score were related (p = 0.019). CONCLUSIONS: These findings add information regarding acute olfactory status following TBI and provide evidence on the importance of assessing olfaction very early post-TBI in order to plan intervention and determine what accident prevention advice will be required for home or work re-integration.

Independence in managing one's finances after traumatic brain injury.

PRIMARY OBJECTIVE: To establish whether the budgeting task of the Instrumental Activities of Daily Living (IADL) Profile discriminates individuals with a traumatic brain injury (TBI) from healthy controls and to identify the nature of the observed difficulties. METHOD: This study tested 27 adults with moderate or severe TBI and 27 controls matched for age, sex and education on the budgeting task of the IADL Profile. The budgeting task is a complex real-world problem involving the preparation of a yearly budget for an individual living on a fixed income with the goal of saving money to purchase a car. MAIN RESULTS: The results showed that TBI subjects, the majority of whom had documented frontal lesions and/or diffuse axonal injury based on CT scan reports, were more likely than control subjects to experience difficulties on all task-related operations (planning, carrying out and verifying attainment of goal), with planning being particularly affected. These deficits were shown to impact on financial abilities, an issue of particular concern for TBI individuals reporting full responsibility of their finances. CONCLUSIONS: The budgeting task of the IADL Profile discriminates TBI subjects from controls. Planning was shown to be the most significant difficulty underlying reduced independence in the task.

Immunohistochemical diagnosis of canine oral amelanotic melanocytic neoplasms.

Definitive diagnosis of canine oral melanocytic neoplasms is often difficult because of variability in pigmentation and cellular pleomorphism. These neoplasms can resemble carcinomas, sarcomas, and round cell neoplasms, which differ in prognosis and treatment. A variety of immunohistochemical antibodies have been used for diagnosis of melanocytic neoplasms in humans and dogs; however, sensitivity and specificity of many markers have not been determined in amelanotic melanocytic neoplasms in dogs. The authors investigated a comprehensive panel of immunohistochemical markers in 49 canine oral amelanotic melanocytic neoplasms--namely, Melan-A, PNL2, HMB-45, microphthalmia transcription factor (MiTF), S-100, tyrosine hydroxylase, tyrosinase, tyrosinase-related proteins 1 and 2 (TRP-1 and TRP-2), and CD34. Ten well-differentiated cutaneous soft tissue spindle cell sarcomas were negative controls. Melan-A, PNL2, TRP-1, and TRP-2 were highly sensitive and 100% specific for the diagnosis of canine oral amelanotic melanocytic neoplasms. S-100 and MiTF showed high sensitivity but were less specific; that is, they also labeled a proportion of the soft tissue spindle cell sarcomas. HMB-45, tyrosinase, and tyrosine hydroxylase were 100% specific but had low sensitivities. CD34 did not label any of the melanocytic neoplasms but did label 80% of the soft tissue spindle cell sarcomas. A cost-effective and efficient immunodiagnostic cocktail containing antibodies against PNL2, Melan-A, TRP-1, and TRP-2 was created that had 100% specificity and 93.9% sensitivity in identifying canine oral amelanotic melanocytic neoplasms. The spindloid variant was the variant with the lowest sensitivity to the cocktail. The likelihood of correctly diagnosing canine oral amelanotic melanocytic neoplasms was dramatically higher when biopsy samples contained ample overlying and adjacent epithelium.

Relevance of measuring diastolic time intervals in the ductus venosus during the early stages of twin-twin transfusion syndrome.

OBJECTIVE: To determine if the discrete myocardial diastolic dysfunction documented previously in the recipient twin during the early stages of twin-twin transfusion syndrome (TTTS) has any repercussion on flow velocities through the ductus venosus (DV) and to investigate if this could allow early differentiation between TTTS and selective intrauterine growth restriction (IUGR). METHODS: Two groups of monochorionic twin pregnancies with growth discordance between twins were reviewed retrospectively. Group I was composed of fetuses in Stages I and II of TTTS; laser or amnioreduction was not performed in any instance. Group II twin pairs each included one fetus with IUGR due to placental circulatory insufficiency. Intertwin differences (smaller minus larger fetus) were analyzed for myocardial performance index of the right ventricle (MPI-RV) and for time variables in the DV. RESULTS: There were 38 pairs of monochorionic twins (24 TTTS and 14 IUGR) in this study. In the TTTS group, the donors had a significantly lower MPI-RV (0.419 +/- 0.18 vs. 0.596 +/- 0.17, F(1,19df) = 24.017, P < 0.001), a significantly longer total ventricular filling time (150.9 +/- 25.6 ms vs. 124.0 +/- 22.6 ms; F(1,21df) = 19.631, P < 0.001) and a significantly longer early filling time (118.9 +/- 22.9 ms vs. 92.6 +/- 18.9 ms, F(1,21df) = 28.419, P < 0.001) than had the recipient. None of these three differences was present in the IUGR group. Probability studies revealed that cut-off values of 12.75 for intertwin differences in total filling time and 8.5 for intertwin differences in early filling time had sensitivities of 71% and 92%, respectively. The false-positive rates were 23% and 15%, respectively, for the early diagnosis of TTTS. CONCLUSION: In monochorionic twin pregnancies, shortening of the ventricular filling time in the recipient twin indicates diastolic myocardial dysfunction occurring early in the pathophysiology of TTTS. This early interwin difference in myocardial function is not found in pregnancies with IUGR in one twin due to placental circulatory insufficiency, allowing early differentiation between TTTS and selective IUGR.

Prediction of the level of cognitive functional independence in acute care following traumatic brain injury.

PRIMARY OBJECTIVE: To determine a predictive model for cognitive functional outcome of patients with traumatic brain injury (TBI) at discharge from acute care. METHODS AND PROCEDURE: Three hundred and thirty-five patients were included in this analysis. Variables considered were age, education, initial score on the Glasgow Coma Scale (GCS), duration of post-traumatic amnesia (PTA), cerebral imaging results and the need for neurosurgical intervention. EXPERIMENTAL INTERVENTIONS: Functional Independence Measure (FIM). MAIN OUTCOMES AND RESULTS: Results of this analysis indicated better cognitive FIM at discharge from acute care settings for patients with TBI when PTA was less than 24 hours, when level of education was higher, when no parietal lesion was identified, when no neurosurgical intervention was required, for patients with TBI who were younger and who presented with a higher GCS score upon admission. CONCLUSIONS: This model will help to plan resource allocation for treatment and discharge planning within the first weeks following TBI.

Early intertwin differences in myocardial performance during the twin-to-twin transfusion syndrome.

BACKGROUND: In the twin-to-twin transfusion syndrome (TTTS), pressure rather than volume overload is increasingly considered as a key factor in the pathogenesis of the cardiomyopathy of the recipient twin. If this is the case, cardiac dysfunction should be among the first signs observed with TTTS. The objective of this study was to determine whether intertwin differences in myocardial function are modified early in the course of TTTS and whether they can help to differentiate this condition from intrauterine growth restriction (IUGR). METHODS AND RESULTS: Eight variables were analyzed on the first fetal echocardiography on 21 pairs of twins with TTTS and 11 with IUGR. No difference was found between the 2 groups for the cardiothoracic ratio, pulsatility indices in the umbilical and middle cerebral arteries, and peak velocity of the middle cerebral artery. Significant difference was found for ventricular septal thickness, but with no association with the conditions under study. With TTTS, left ventricular shortening fraction was consistently greater in the donor twins, and myocardial performance indices (MPIs) were elevated in the recipient twins. This increase in MPI was caused by a lengthening of the isovolumic periods compared with those of the donor twin: left ventricular and right ventricular isovolumic periods 0.105+/-0.047 and 0.097+/-0.026 seconds, respectively, for the recipient twins versus 0.0561+/-0.46 and 0.065+/-0.03 seconds, respectively, for the donor twins (P<0.001). These changes in the isovolumic periods were mainly due to significant prolongation of isovolumic relaxation times. A change in left ventricular MPI > or =0.09 combined with a change in right ventricular MPI > or =0.05 would identify a TTTS with a sensitivity of 75% and a false-positive rate of 9%. CONCLUSIONS: The observed diastolic function impairment goes along with the pressure-overload pathogenic concept proposed in TTTS. Assessment of intertwin difference in MPI is a valuable tool for early differential diagnosis between TTTS and isolated IUGR.

Child victims of dog bites treated in emergency departments: a prospective survey.

UNLABELLED: The study was conducted to determine the characteristics of child victims of dog bite accidents. Pediatricians and nurses prospectively collected standardized information on all child victims of dog bites brought in for treatment to six hospital emergency departments (three urban university teaching hospitals and three rural hospitals). One hundred completed questionnaires were collected and analyzed. The frequency of dog bites brought for care to the emergency departments was equivalent to about one-quarter of all road traffic casualties and one-third of burns at home. Of the 100 victims, 65 were bitten at home, and 35 in a public place. The bite accidents that occurred at home concerned children with a median age of 5 years, who were without adult supervision at the time of the accident. The children who were bitten by dogs in public places had a median age of 9 years. For 77 bites, the dog was not familiar to the child. Based on the history, it appeared that 56 out of 65 accidents at home and 11 out of 35 in public places resulted mainly from the children's or adult's behavior. CONCLUSION: To reduce the frequency of dog bites both at home and in public places, education could be the preventive measure with the highest priority. Out of 100 accidents, 67 children might not have been bitten had they and their parents been adequately educated on safe conduct towards dogs.

Lack of CD40-dependent B-cell proliferation in B lymphocytes isolated from patients with persistent polyclonal B-cell lymphocytosis.

Persistent B-cell lymphocytosis (PPBL) is a haematological disorder diagnosed primarily in adult female smokers that is characterized by a polyclonal increase in peripheral blood B lymphocytes and a moderate elevation of serum IgM. B lymphocyte-associated cellular abnormalities, such as the occurrence of multi-lobed nuclei, increased bcl2/Ig gene rearrangements and the identification of an extra long-arm chromosome (i3)(q10) in the B-cell population, indicate that PPBL could be part of a multi-step process leading to the emergence of a malignant B lymphoproliferation. However, the resulting impact on cellular functional properties remains to be elucidated. Our goal was to address that aspect via the study of B-cell activity following stimulation through CD40, a key molecule of the tumour necrosis factor receptor superfamily involved in B lymphocyte development. In contrast to normal B cells, PPBL B lymphocytes were unable to respond to the proliferative signal delivered in vitro by CD40, indicating a defect in the CD40 activation pathway. Polymerase chain reaction amplification and sequencing of the receptor as well as FACScan analysis of patient B lymphocytes dismissed the possibility of a defect in either CD40 structure or expression. Moreover, Western blot analysis of tyrosine phosphorylation, an early event in the CD40-signalling cascade, was similar in patients and controls, leading to the conclusion that the defect affecting B lymphocytes in PPBL patients is probably located downstream of that signalling cascade.

Cloning, over-expression and purification of Pseudomonas aeruginosa murC encoding uridine diphosphate N-acetylmuramate: L-alanine ligase.

We cloned and sequenced the murC gene from Pseudomonas aeruginosa encoding a protein of 53 kDa. Multiple alignments with 20 MurC peptide sequences from different bacteria confirmed the presence of highly conserved regions having sequence identities ranging from 22-97% including conserved motifs for ATP-binding and the active site of the enzyme. Genetic complementation was done in Escherichia coli (murCts) suppressing the lethal phenotype. The murC gene was subcloned into the expression vector pET30a and overexpressed in E. coli BL21(lambdaDE3). Three PCR cloning strategies were used to obtain the three recombinant plasmids for expression of the native MurC, MurC His-tagged at N-terminal and at C-terminal, respectively. MurC His-tagged at C-terminal was chosen for large scale production and protein purification in the soluble form. The purification was done in a single chromatographic step on an affinity nickel column and obtained in mg quantities at 95% homogeneity. MurC protein was used to produce monoclonal antibodies for epitope mapping and for assay development in high throughput screenings. Detailed studies of MurC and other genes of the bacterial cell cycle will provide the reagents and strain constructs for high throughput screening and for design of novel antibacterials.

Results of surgical treatment of Sprengel deformity by a modified Green's procedure.

The results of treatment of seven children with Sprengel deformity are reviewed. The patients were subjected to a modified Green procedure without dissection of the serratus anterior muscle and immediate postoperative mobilization. The results seem to indicate that the postoperative abduction gain (77 degrees) compares favorably in regard to the current literature and that this modification of the classic technique offers a substantial advantage concerning functional outcome in these patients.

Hippocampal lesions interfere with Pavlovian negative occasion setting.

Rats were trained with either a serial feature positive (L-->T1+ T-) or a serial feature negative (L-->T1-, T1+) discrimination, intermixed with training on another, nonconditional discrimination (T2+, N-), using a Pavlovian appetitive conditioning preparation with multiple response measures. Among rats trained with the serial feature positive discrimination, neurotoxic lesions of the hippocampus produced a transient impairment in the acquisition of that discrimination, but did not affect acquisition of the nonconditional discrimination. In contrast, among rats that received serial feature negative discrimination training, hippocampal lesions produced enduring deficits in the acquisition of both discriminations. The results of transfer tests indicated that both lesioned and control rats used a conditional learning strategy (occasion setting) to solve the feature positive and feature negative discriminations. Furthermore, lesioned rats, especially those that received training with the feature negative discrimination, displayed increasingly higher levels of general activity as training progressed. The results suggest that hippocampal lesions particularly interfere with inhibitory learning (negative occasion setting) about both explicit and contextual cues.

Patient evaluation of treatment success as related to denture tooth type.

PURPOSE: Tooth selection is considered an important factor in the construction of complete dentures that function harmoniously and comfortably and preserve the denture-supporting tissues. To bring a scientific background to clinical impressions, the hypothesis that different cusp angles bring different levels of patient satisfaction was tested. MATERIALS AND METHODS: Four different occlusal schemes were compared. The dependent variables (3 groups of visual analogue scores of patient satisfaction) were analyzed by means of multivariate analysis of variance (MANOVA) for repeated measures. RESULTS: All MANOVAs showed nonsignificant results for the effect of tooth type on the 3 groups of variables (P values between 0.1 and 0.8). CONCLUSION: The results did not show statistically significant differences in patient satisfaction among the different occlusal schemes. It is recommended that future research use more sensitive instruments to evaluate this specific aspect of treatment success.

Stress fracture of the acetabular roof. Case report and value of MRI.

The authors report the case of an 11-year-old boy with pain in the left leg without history of recent trauma. The diagnosis of a stress fracture of the acetabulum was made based on MRI and bone marrow biopsy. They discuss the role of MRI in the diagnosis of a stress fracture.

Occasion setting: a neural network approach.

Classical conditioning data show that a conditioned stimulus (CS) can act either as a simple CS--eliciting conditioned responses (CRs) by signaling the occurrence of an unconditioned stimulus (US)--or as an occasion setter--controlling the responses generated by another CS. In this article, the authors apply a simple extension of a network model of conditioning, originally presented by N. A. Schmajuk and J. J. DiCarlo (S-D; 1992), to the description of these 2 different CS functions. In the model, CS inputs are connected to the CR output both directly and indirectly through a hidden unit layer that codes configural stimuli. In this framework, a CS acts as (a) a simple stimulus through its direct connections with the output units and as (b) an occasion setter through its indirect configural connections via the hidden units. Computer simulations demonstrate that the network accounts for a large part of the data on occasion setting.

Absence of metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by flavin-containing monooxygenase (FMO).

The N-nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent lung carcinogen present in tobacco and tobacco smoke. Carbonyl reduction, alpha-carbon hydroxylation (activation) and N-oxidation of the pyridyl ring (detoxification) are the three main pathways of metabolism of NNK. In this study, metabolism of NNK was studied with lung and liver microsomes from F344 rats, Syrian golden hamsters and pigs and cloned flavin-containing monooxygenases (FMOs) from human and rabbit liver. Thermal inactivation at 45 degrees C for 2 min reduced FMO S-oxygenating activity but did not affect N-oxidation of NNK, leading to the conclusion that FMOs are not implicated in the detoxification of NNK. Detoxification of NNK was not increased by n-octylamine or by incubation at pH 8.4, supporting the conclusion that FMOs are not involved in the metabolism of NNK. SKF-525A (1 mM) significantly reduced N-oxidation and alpha-carbon hydroxylation, suggesting that these two pathways were catalyzed by cytochromes P450. Metabolism of NNK was lower with lung microsomes than with liver microsomes. Inhibition of metabolism of NNK by SKF-525A was also observed with rat lung microsomes, leading to the conclusion that cytochromes P450 are involved in pulmonary metabolism of NNK. Cloned FMOs did not metabolize NNK. In conclusion, cytochromes P450 rather than FMOs are involved in N-oxidation of NNK. The high capacity of hamster liver microsomes to activate NNK does not correlate with the resistance of this tissue to NNK-induced hepatocarcinogenesis.