Looks Like FH But it’s not FH: Extended Lipid Profile of Paediatric Clinical FH Patients Reveals a Different Lipid Profile in FH Negative Patients

Aim: Familial Hypercholesterolemia (FH) is a common autosomal dominant disorder, caused by mutations in genes involved in cholesterol’s clearance (LDLR, APOB, PCSK 9). Clinical diagnosis is usually based on high total cholesterol or LDL-C levels and family history of premature coronary heart disease. Using an extended lipid profile of paediatric dyslipidemic patients, we aim to identify biomarkers for a better diagnosis of FH in clinical settings.

Pocket handbook for the recognition and diagnosis of certain animal diseases exotic to most of the Americas /

Microfiche sheets have title: Clinical diagnosis of selected diseases exotic to most of the Americas.

Diagnosis of autistic spectrum disorders in Queensland: Variations in practice

Objective: For both paediatricians and child psychiatrists, referrals to assess possible autistic spectrum disorders (ASD) are increasing. This study examines current practices of medical specialists in the assessment of these disorders. Methods: An anonymous, self-report questionnaire was sent to all Queensland paediatricians and child psychiatrists. The survey elicited frequencies of consultation for ASD, diagnostic method, advice provided and perceived adequacy of training for this work. Results: Responses were received from 79 (85%) eligible paediatricians and 26 (58%) eligible child psychiatrists. For one-third of all clinicians, new consultations for possible ASD occurred as often as 2-3 times per week. Most specialists approached the clinical diagnosis of ASD by considering history from different sources and professional assessments. Paediatricians (86%) were more likely than child psychiatrists (62%) to request genetic studies for children with severe autism (P = 0.01). Both general paediatricians and developmental paediatricians perceived level of training for possible ASD consultations was significantly worse than child psychiatrists (P < 0.001 and P = 0.02, respectively), but no difference was found between paediatric groups (P = 0.27). Perceived adequacy of specialist training was not associated with length of experience in clinical practice. Conclusion: Medical practice in Queensland around diagnosis of ASD is characterized by considerable variability. There is still a long way to go if we are to achieve consistency around medical issues of organic diagnosis and practices impacting on health as well as consideration of differential developmental diagnoses. The finding that recently trained paediatricians felt just as unprepared for this work as their older colleagues suggests that the graduate training response to this 'new morbidity' has not been adequate.

A study of potential serum markers for a diagnosis of gram-positive and gram-negative bacterial sepsis

Sepsis continues to be a major cause of morbidity and mortality as it can readily lead tosevere sepsis, septic shock, multiple organ failure and death. The onset can be rapid and difficult to define clinically. Despite the numerous candidate markers proposed in the literature, to date a serum marker for sepsis has not been found. The aim of this study was to assay the serum of clinically diagnosed patients with eithera Gram-negative or Gram- positive bacterial sepsis for elevated levels of nine potentialmarkers of sepsis, using commercially produced enzyme linked immunosorbent assays(ELISA). The purpose was to find a test marker for sepsis that would be helpful toclinicians in cases of uncertain sepsis and consequently expose false positive BC'scaused by skin or environmental contaminants. Nine test markers were assayed including IL-6, IL-I 0, ILI2, TNF-α, lipopolysaccharide binding protein, procalcitonin, sE-selectin, sICAM -1 and a potential differential marker for Gram-positive sepsis- anti-lipid S antibody. A total of 445 patients were enrolled into this study from the Queen Elizabeth Hospital and Selly Oak Hospital (Birmingham). The results showed that all the markers were elevated in patients with sepsis and that patients with a Gram-negative sepsis consistently produced higher median/range serum levels than those with a Gram-positive sepsis. No single marker was able to identify all the septic patients. Combining two markers caused the sensitivities and specificities for a diagnosis of sepsis to increase to within a 90% to 100% range. By a process of elimination the markers that survived into the last phase were IL-6 with sICAM -1, and anti-lipid S IgG assays Defining cut-off levels for a diagnosis of sepsis became problematic and a semi-blind trial was devised to test the markers in the absence of both clinical details and positive blood cultures. Patients with pyrexia of unknown origin and negative BC were included in this phase (4). The results showed that IL-6 with sICAM-l are authentic markers of sepsis. There was 82% agreement between the test marker diagnosis and the clinical diagnosis for sepsis in patients with a Gram-positive BC and 78% agreement in cases of Gram-negative Be. In the PUO group the test markers identified 12 cases of sepsis and the clinical diagnosis 15. The markers were shown to differentiate between early sepsis and sepsis, inflammatory responses and infection. Anti-lipid S with IL-6 proved be a sensitive marker for Gram-positive infections/sepsis.

Clinical studies of spatial and temporal aspects of vision: an investigation using psychophysical and electrophysiological techniques

Separate physiological mechanisms which respond to spatial and temporal stimulation have been identified in the visual system. Some pathological conditions may selectively affect these mechanisms, offering a unique opportunity to investigate how psychophysical and electrophysiological tests reflect these visual processes, and thus enhance the use of the tests in clinical diagnosis. Amblyopia and optical blur were studied, representing spatial visual defects of neural and optical origin, respectively. Selective defects of the visual pathways were also studied - optic neuritis which affects the optic nerve, and dementia of the Alzheimer type in which the higher association areas are believed to be affected, but the primary projections spared. Seventy control subjects from 10 to 79 years of age were investigated. This provided material for an additional study of the effect of age on the psychophysical and electrophysiological responses. Spatial processing was measured by visual acuity, the contrast sensitivity function, or spatial modulation transfer function (MTF), and the pattern reversal and pattern onset-offset visual evoked potential (VEP). Temporal, or luminance, processing was measured by the de Lange curve, or temporal MTF, and the flash VEP. The pattern VEP was shown to reflect the integrity of the optic nerve, geniculo striate pathway and primary projections, and was related to high temporal frequency processing. The individual components of the flash VEP differed in their characteristics. The results suggested that the P2 component reflects the function of the higher association areas and is related to low temporal frequency processing, while the Pl component reflects the primary projection areas. The combination of a delayed flash P2 component and a normal latency pattern VEP appears to be specific to dementia of the Alzheimer type and represents an important diagnostic test for this condition.

Eye movement problems and differential diagnosis of the parkinsonian syndromes

Differential clinical diagnosis of the parkinsonian syndromes, viz., Parkinson’s disease (PD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) can be difficult. Eye movement problems, however, are a chronic complication of many of these disorders and may be a useful aid to diagnosis. Hence, the presence in PSP of vertical supranuclear gaze palsy, fixation instability, lid retraction, blepharospasm, and apraxia of eyelid opening and closing is useful in separating PD from PSP. Moreover, atypical features of PSP include slowing of upward saccades, moderate slowing of downward saccades, the presence of a full range of voluntary vertical eye movements, a curved trajectory of oblique saccades, and absence of square-wave jerks. Downgaze palsy is probably the most useful diagnostic clinical symptom of PSP. By contrast, DLB patients are specifically impaired in both reflexive and saccadic execution and in the performance of more complex saccadic eye movement tasks. Problems in convergence in DLB are also followed by akinesia and rigidity. Abnormal ocular fixation may occur in a significant proportion of MSA patients along with excessive square-wave jerks, a mild supranuclear gaze palsy, a gaze-evoked nystagmus, a positioning down-beat nystagmus, mild-moderate saccadic hypometria, impaired smooth pursuit movements, and reduced vestibulo-ocular reflex (VOR) suppression. There may be considerable overlap between the eye movement problems characteristic of the various parkinsonian disorders, but taken together with other signs and symptoms, can be a useful aid in differential diagnosis, especially in the separation of PD and PSP.

Impact of suspected food allergy on emotional distress and family life of parents prior to allergy diagnosis

Background: Food allergy is associated with psychological distress in both child and parent. It is unknown whether parental distress is present prior to clinical diagnosis or whether experiences at clinic can reduce any distress present. This study aimed to assess anxiety and depression in parents and the impact of suspected food allergy on the lives of families before and after a visit to an allergy clinic. Methods: One hundred and twenty-four parents visiting an allergy clinic for the first time to have their child assessed for food allergy completed a study-specific questionnaire and the Hospital Anxiety and Depression Scale; 50 parents completed these 4-6 wk later in their own home. Results: Most parents (86.4%) reported suspected food allergy had an impact on their family life prior to clinic attendance; 76% had made changes to their child's diet. 32.5% of parents had mild-to-severe anxiety before their clinic visit; 17.5% had mild-to-moderate depression. Post-clinic, 40% had mild-to-severe anxiety; 13.1% had mild-to-moderate depression. There were no significant differences in anxiety (p = 0.34) or depression scores (p = 0.09) before and after the clinic visit. Conclusions: Anxiety and depression is present in a small proportion of parents prior to diagnosis of food allergy in their child and this does not reduce in the short term after the clinic visit. Identification of parents at risk of suffering from distress is needed and ways in which we communicate allergy information before and at clinic should be investigated to see if we can reduce distress. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ambulatory electroencephalogram in children:a prospective clinical audit of 100 cases

Ambulatory electroencephalogram has been used for differentiating epileptic from nonepileptic events, recording seizure frequency and classification of seizure type. We studied 100 consecutive children prospectively aged 11 days to 16 years that were referred for an ambulatory electroencephalogram to a regional children's hospital. Ambulatory electroencephalogram was clinically useful in contributing to a clinical diagnosis in 71% of children who were referred with a range of clinical questions. A diagnosis of epileptic disorder was confirmed by obtaining an ictal record in 26% and this included 11 children that had previously normal awake and or sleep electroencephalogram. We recommend making a telephone check of the current target event frequency and prioritising those with typical events on most days in order to improve the frequency of recording a typical attack.

Signposting for diagnosis of Autism Spectrum Disorder using the Diagnostic Interview for Social and Communication Disorders (DISCO)

Recent research has investigated the capability of the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) descriptions to identify individuals who should receive a diagnosis of Autism Spectrum Disorder (ASD) using standardised diagnostic instruments. Building on previous research investigating behaviours essential for the diagnosis of DSM-5 ASD, the current study investigated the sensitivity and specificity of a set of 14 items derived from the Diagnostic Interview for Social and Communication Disorders (DISCO Signposting set) that have potential for signposting the diagnosis of autism according to both the new DSM-5 criteria for ASD and ICD-10 criteria for Childhood Autism. An algorithm threshold for the Signposting set was calculated in Sample 1 (n = 67), tested in an independent validation sample (Sample 2; n = 78), and applied across age and ability sub-groups in Sample 3 (n = 190). The algorithm had excellent predictive validity according to best estimate clinical diagnosis (Samples 1 and 2) and excellent agreement with established algorithms for both DSM-5 and ICD-10 (all samples). The signposting set has potential to inform our understanding of the profile of ASD in relation to other neurodevelopmental disorders and to form the basis of a Signposting Interview for use in clinical practice.

The tuberous sclerosis 2000 study:presentation initial assessments and implications for diagnosis and management

Aims: The Tuberous Sclerosis 2000 Study is the first comprehensive longitudinal study of tuberous sclerosis (TS) and aims to identify factors that determine prognosis. Mode of presentation and findings at initial assessments are reported here. Methods: Children aged 0-16 years newly diagnosed with TS in the UK were evaluated. Results: 125 children with TS were studied. 114 (91%) met clinical criteria for a definite diagnosis and the remaining 11 (9%) had pathogenic TSC1 or TSC2 mutations. In families with a definite clinical diagnosis, the detection rate for pathogenic mutations was 89%. 21 cases (17%) were identified prenatally, usually with abnormalities found at routine antenatal ultrasound examination. 30 cases (24%) presented before developing seizures and in 10 of these without a definite diagnosis at onset of seizures, genetic testing could have confirmed TS. 77 cases (62%) presented with seizures. Median age at recruitment assessment was 2.7 years (range:4 weeks-18 years). Dermatological features of TS were present in 81%. The detection rate of TS abnormalities was 20/107 (19%) for renal ultrasound including three cases with polycystic kidney disease, 51/88 (58%) for echocardiography, 29/35 (83%) for cranial CT and 95/104 (91%) for cranial MRI. 91% of cases had epilepsy and 65% had intellectual disability (IQ<70). Conclusions: Genetic testing can be valuable in confirming the diagnosis. Increasing numbers of cases present prenatally or in early infancy, before onset of seizures, raising important questions about whether these children should have EEG monitoring and concerning the criteria for starting anticonvulsant therapy.

Structural determination and gynecological tumor diagnosis using antibody chip captured proteins

Purpose: To identify markers for gynecological tumor diagnosis using antibody chip capture. Methods: Marker proteins, including cancer antigen 153 (CA153), CA125, and carcinoembryonic antigen (CEA), were analyzed using antibody chip capture of serum samples. Fifteen agglutinin types that specifically recognized five common glycans (fucose, sialic acid, mannose, N - acetylgalactosamine, and N-acetylglucosamine) were used to detect marker protein glycan levels. The levels of CA153, CA125, and CEA from 49 healthy control samples, 31 breast cancer samples, 24 cervical cancer samples, and 19 ovarian cancer samples were used to measure the glycan levels of these marker proteins. Results: In breast cancer samples, CA153 and CA125 were down-regulated (p < 0.01), while differences in ovarian cancer samples were not statistically significant (p > 0.01). The total accuracy was 85.1 %, with 96.8 % accuracy for breast cancer, 75 % in cervical cancer, and 78.9 % in ovarian cancer. Cross-validation analyses showed that breast cancer had 93.5 % accuracy, cervical cancer was 66.7 %, and ovarian cancer was 68.4 %, leading to 78.4 % total accuracy (58/74). Conclusions: The results indicate that better clinical diagnosis of gynecological tumors can be obtained by monitoring changes in glycan levels of serum proteins and types of proteoglycan changes.

Evaluation of alpha-synuclein RT-QuIC for an early and differential diagnosis of Lewy body disease

Synucleinopathies are a group of neurodegenerative diseases characterized by tissue deposition of insoluble aggregates of the protein α-synuclein. Currently, the clinical diagnosis of these diseases, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), is very challenging, especially at an early disease stage, due to the heterogeneous and often non-specific clinical manifestations. Therefore, identifying specific biomarkers to aid the diagnosis and improve the clinical management of patients with these disorders represents a primary goal in the field. Pursuing this aim, we applied the α-Syn Real-Time Quaking-Induced Conversion (RT-QuIC), an ultrasensitive technique able to detect minute amounts of amyloidogenic proteins, to a large cohort of 953 CSF samples from clinically well-characterized (“clinical” group), or neuropathologically verified (“NP” group) patients with parkinsonism or dementia. Of significance, we also studied patients with prodromal synucleinopathies (“prodromal” group), such as pure autonomic failure (PAF) (n = 28), isolated REM sleep behavior disorder (iRBD) (n = 18), and mild cognitive impairment due to probable Lewy body (LB) disease (MCI-LB) (n = 81). Our findings show that α-syn RT-QuIC can accurately detect α-Syn seeding activity across the whole spectrum of LB-related disorders (LBD), exhibiting a mean sensitivity of 95.2% in the “clinical” and “NP” group, while ranging between 89.3% (PAF) and 100% (RBD) in the “prodromal group”. Moreover, we observed 95.1% sensitivity and 96.6% specificity in the distinction between MCI-LB patients and cognitively unimpaired controls, demonstrating the solid diagnostic potential of α-Syn RT-QuIC in the early phase of the disease. Finally, 13.3% of MCI-AD patients also had a positive test, suggesting an underlying LB co-pathology. This work demonstrated that α-Syn RT-QuIC is an efficient assay for accurate and early diagnosis of LBD, which should be implemented for clinical management and recruitment for clinical trials in memory clinics.

Ressonância magnética e características clínicas em adultos com doenças desmielinizantes monofásicas: encefalomielite aguda disseminada ou uma variante da esclerose múltipla?

Acute disseminated encephalomyelitis (ADEM) is a widespread monophasic inflamatory disease affecting the central nervous system, that usually follows an infection or vaccination. In this study, we present an analysis of magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) and clinical aspects in four patients with clinical diagnosis of ADEM. The presence of MRI demyelinating lesions was crucial, but not in itself sufficient for definitive diagnosis. Clinical and MRI follow up, in order to exclude new lesions and to reevaluate the former ones, as well as CSF, were important for the differential diagnosis with other demyelinating diseases, particularly multiple sclerosis. In addition, we have shown that early treatment with methylprednisolone after the initial symptoms was effective for improving clinical manifestations as well as for reducing MRI lesions.

Metodo de reconstrução tridimensional para avaliação postural

Universidade Estadual de Campinas. Faculdade de Educação Física

Hidróxidos duplos lamelares: nanopartículas inorgânicas para armazenamento e liberação de espécies de interesse biológico e terapêutico

Studies about the inorganic nanoparticles applying for non-viral release of biological and therapeutic species have been intensified nowadays. This work reviews the preparation strategies and application of layered double hydroxides (LDH) as carriers for storing, carrying and control delivery of intercalated species as drugs and DNA for gene therapy. LDH show low toxicity, biocompatibility, high anion exchange capacity, surface sites for functionalization, and a suitable equilibrium between chemical stability and biodegradability. LDH can increase the intercalated species stability and promote its sub-cellular uptake for biomedical purposes. Concerning the healthy field, LDH have been evaluated for clinical diagnosis as a biosensor component.