Basic principles of design and functioning of multifunctional laser diagnostic system for non-invasive medical spectrophotometry

The devising of a general engineering theory of multifunctional diagnostic systems for non-invasive medical spectrophotometry is an important and promising direction of modern biomedical engineering. We aim in this study to formalize in scientific engineering terms objectives for multifunctional laser non-invasive diagnostic system (MLNDS). The structure-functional model as well as a task-function of generalized MLNDS was formulated and developed. The key role of the system software for MLNDS general architecture at steps of ideological-technical designing has been proved. The basic principles of block-modules composition of MLNDS hardware are suggested as well. © 2011 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

The blood perfusion and NADH/FAD content combined analysis in patients with diabetes foot

Skin blood microcirculation and the metabolism activity of tissue were examined on the patients with type 2 diabetes. Laser Doppler flowmetry (LDF) with 1064 nm laser light source and fluorescence spectroscopy (FS) with excitation light of 365 nm and 450 nm have been used to monitor the blood perfusion and the content of coenzymes NADH and FAD. Concluding, the proposed combined LDF and tissue FS approach allows to identify the significant violations in the blood microcirculation and metabolic activity for type 2 diabetes patients.

Alzheimer's disease and vision: a proposed new diagnostic test

A potential non-invasive neurobiological test for Alzheimer's disease has been recently proposed and published. This test is likely to be of considerable interest to optometrists as it involves measurements of pupil dilation. This article decsribes some of the controversial issues surrounding the clinical diagnosis of Alzheimer's disease and discusses the advantages, limitations, and implications of the new test.

Herbal medicines:physician's recommendation and clinical evaluation of St.John's Wort for depression

Why some physicians recommend herbal medicines while others do not is not well understood. We undertook a survey designed to identify factors, which predict recommendation of herbal medicines by physicians in Malaysia. About a third (206 out of 626) of the physicians working at the University of Malaya Medical Centre ' were interviewed face-to-face, using a structured questionnaire. Physicians were asked about their personal use of, recommendation of, perceived interest in and, usefulness and safety of herbal medicines. Using logistic regression modelling we identified personal use, general interest, interest in receiving training, race and higher level of medical training as significant predictors of recommendation. St. John's wort is one of the most widely used herbal remedies. It is also probably the most widely evaluated herbal remedy with no fewer than 57 randomised controlled trials. Evidence from the depression trials suggests that St. John's wort is more effective than placebo while its comparative efficacy to conventional antidepressants is not well established. We updated previous meta-analyses of St. John's wort, described the characteristics of the included trials, applied methods of data imputation and transformation for incomplete trial data and examined sources of heterogeneity in the design and results of those trials. Thirty randomised controlled trials, which were heterogeneous in design, were identified. Our meta-analysis showed that St. John's wort was significantly more effective than placebo [pooled RR 1.90 (1.54-2.35)] and [Pooled WMD 4.09 (2.33 to 5.84)]. However, the remedy was similar to conventional antidepressant in its efficacy [Pooled RR I. 0 I (0.93 -1.10)] and [Pooled WMD 0.18 (- 0.66 to 1.02). Subgroup analyses of the placebo-controlled trials suggested that use of different diagnostic classifications at the inclusion stage led to different estimates of effect. Similarly a significant difference in the estimates of efficacy was observed when trials were categorised according to length of follow-up. Confounding between the variables, diagnostic classification and length of trial was shown by loglinear analysis. Despite extensive study, there is still no consensus on how effective St. lohn's wort is in depression. However, most experts would agree that it has some effect. Our meta-analysis highlights the problems associated with the clinical evaluation of herbal medicines when the active ingredients are poorly defined or unknown. The problem is compounded when the target disease (e.g. depression) is also difficult to define and different instruments are available to diagnose and evaluate it.

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.

Optimising the clinical analysis of retinal image quality in the human eye

Visual perception is dependent on both light transmission through the eye and neuronal conduction through the visual pathway. Advances in clinical diagnostics and treatment modalities over recent years have increased the opportunities to improve the optical path and retinal image quality. Higher order aberrations and retinal straylight are two major factors that influence light transmission through the eye and ultimately, visual outcome. Recent technological advancements have brought these important factors into the clinical domain, however the potential applications of these tools and considerations regarding interpretation of data are much underestimated. The purpose of this thesis was to validate and optimise wavefront analysers and a new clinical tool for the objective evaluation of intraocular scatter. The application of these methods in a clinical setting involving a range of conditions was also explored. The work was divided into two principal sections: 1. Wavefront Aberrometry: optimisation, validation and clinical application The main findings of this work were: • Observer manipulation of the aberrometer increases variability by a factor of 3. • Ocular misalignment can profoundly affect reliability, notably for off-axis aberrations. • Aberrations measured with wavefront analysers using different principles are not interchangeable, with poor relationships and significant differences between values. • Instrument myopia of around 0.30D is induced when performing wavefront analysis in non-cyclopleged eyes; values can be as high as 3D, being higher as the baseline level of myopia decreases. Associated accommodation changes may result in relevant changes to the aberration profile, particularly with respect to spherical aberration. • Young adult healthy Caucasian eyes have significantly more spherical aberration than Asian eyes when matched for age, gender, axial length and refractive error. Axial length is significantly correlated with most components of the aberration profile. 2. Intraocular light scatter: Evaluation of subjective measures and validation and application of a new objective method utilising clinically derived wavefront patterns. The main findings of this work were: • Subjective measures of clinical straylight are highly repeatable. Three measurements are suggested as the optimum number for increased reliability. • Significant differences in straylight values were found for contact lenses designed for contrast enhancement compared to clear lenses of the same design and material specifications. Specifically, grey/green tints induced significantly higher values of retinal straylight. • Wavefront patterns from a commercial Hartmann-Shack device can be used to obtain objective measures of scatter and are well correlated with subjective straylight values. • Perceived retinal stray light was similar in groups of patients implanted with monofocal and multi focal intraocular lenses. Correlation between objective and subjective measurements of scatter is poor, possibly due to different illumination conditions between the testing procedures, or a neural component which may alter with age. Careful acquisition results in highly reproducible in vivo measures of higher order aberrations; however, data from different devices are not interchangeable which brings the accuracy of measurement into question. Objective measures of intraocular straylight can be derived from clinical aberrometry and may be of great diagnostic and management importance in the future.

Imaging of the human fundus in the clinical setting:past present and future

The human fundus is a complex structure that can be easily visualized and the world of ophthalmology is going through a golden era of new and exciting fundus imaging techniques; recent advances in technology have allowed a significant improvement in the imaging modalities clinicians have available to formulate a diagnostic and treatment plan for the patient, but there is constant on-going work to improve current technology and create new ideas in order to gather as much information as possible from the human fundus. In this article we shall summarize the imaging techniques available in the standard medical retina clinic (i.e. not limited to the research lab) and delineate the technologies that we believe will have a significant impact on the way clinicians will assess retinal and choroidal pathology in the not too distant future.

The psychological impact of diagnostic food challenges to confirm the resolution of peanut or tree nut allergy

Background - Twenty percent of children outgrow peanut allergy and 10% outgrow tree nut allergy. Resolution can be confirmed by a food challenge. Little is known about the psychosocial impact of the challenge. We aimed to investigate effects of a food challenge on anxiety, stress and quality of life (QoL) in children and their mothers on the day of a food challenge to peanuts or nuts, and in the months following the challenge. Methods - One hundred and three families participated. Forty children undergoing food challenges to access resolution of allergy, and their mothers, completed validated questionnaires to measure generic and food specific quality of life, stress and anxiety prior to challenge, on the day of investigation and 3–6 months later. Sixty-three children with no clinical indication to challenge (i.e. in the opinion of the allergist had persistent allergy) acted as comparison group completing questionnaires 3–6 months apart. Results - Mothers reported raised anxiety on the day of challenge (P = 0.007), but children were less anxious. The children (P = 0.01) and mothers (P = 0.01) had improved food-related, but not general, QoL 3–6 months following challenge. Children reported lower anxiety levels following the challenge (P = 0.02), but anxiety remained unchanged in mothers. The improvements in maternal and children's QoL and anxiety levels were irrespective of the challenge outcome and despite co-existing food allergies in 50% of children. Conclusions - Mothers experienced increased anxiety on the day of food challenge, unlike the children, perhaps reflecting the differences in their perceived risks. Food challenges are associated with improved food-related QoL in the following months even in those with a positive challenge.

The predictive ability of clinical tests for contact lens induced dry eye

Approximately half of current contact lens wearers suffer from dryness and discomfort, particularly towards the end of the day. Contact lens practitioners have a number of dry eye tests available to help them to predict which of their patients may be at risk of contact lens drop out and advise them accordingly. This thesis set out to rationalize them to see if any are of more diagnostic significance than others. This doctorate has found: (1) The Keratograph, a device which permits an automated, examiner independent technique for measuring non invasive tear break up time (NITBUT) measured NITBUT consistently shorter than measurements recorded with the Tearscope. When measuring central corneal curvature the spherical equivalent power of the cornea was measured as being significantly flatter than with a validated automated keratometer. (2) Non-invasive and invasive tear break-up times significantly correlated to each other, but not the other tear metrics. Symptomology, assessed using the OSDI questionnaire, correlated more with those tests indicating possible damage to the ocular surface (including LWE, LIPCOF and conjunctival staining) than with tests of either tear volume or stability. Cluster analysis showed some statistically significant groups of patients with different sign and symptom profiles. The largest cluster demonstrated poor tear quality with both non-invasive and invasive tests, low tear volume and more symptoms. (3) Care should be taken in fitting patients new to contact lenses if they have a NITBUT less than 10s or an OSDI comfort rating greater than 4.2 as they are more likely to drop-out within the first 6 months. Cluster analysis was not found to be beneficial in predicting which patients will succeed with lenses and which will not. A combination of the OSDI questionnaire and a NITBUT measurement was most useful both in diagnosing dry eye and in predicting contact lens drop out.

The influence of patient's age on clinical decision-making about coronary heart disease in the USA and the UK

This paper examines UK and US primary care doctors' decision-making about older (aged 75 years) and midlife (aged 55 years) patients presenting with coronary heart disease (CHD). Using an analytic approach based on conceptualising clinical decision-making as a classification process, it explores the ways in which doctors' cognitive processes contribute to ageism in health-care at three key decision points during consultations. In each country, 56 randomly selected doctors were shown videotaped vignettes of actors portraying patients with CHD. The patients' ages (55 or 75 years), gender, ethnicity and social class were varied systematically. During the interviews, doctors gave free-recall accounts of their decision-making. The results do not establish that there was substantial ageism in the doctors' decisions, but rather suggest that diagnostic processes pay insufficient attention to the significance of older patients' age and its association with the likelihood of co-morbidity and atypical disease presentations. The doctors also demonstrated more limited use of 'knowledge structures' when diagnosing older than midlife patients. With respect to interventions, differences in the national health-care systems rather than patients' age accounted for the differences in doctors' decisions. US doctors were significantly more concerned about the potential for adverse outcomes if important diagnoses were untreated, while UK general practitioners cited greater difficulty in accessing diagnostic tests.

Microarray-formatted clinical biomarker assay development using peptide aptamers to anterior gradient-2

Anterior gradient-2 protein was identified using proteomic technologies as a p53 inhibitor which is overexpressed in human cancers, and this protein presents a novel pro-oncogenic target with which to develop diagnostic assays for biomarker detection in clinical tissue. Combinatorial phage-peptide libraries were used to select 12 amino acid polypeptide aptamers toward anterior gradient-2 to determine whether methods can be developed to affinity purify the protein from clinical biopsies. Selecting phage aptamers through four rounds of screening on recombinant human anterior gradient-2 protein identified two classes of peptide ligand that bind to distinct epitopes on anterior gradient-2 protein in an immunoblot. Synthetic biotinylated peptide aptamers bound in an ELISA format to anterior gradient-2, and substitution mutagenesis further minimized one polypeptide aptamer to a hexapeptide core. Aptamers containing this latter consensus sequence could be used to affinity purify to homogeneity human anterior gradient-2 protein from a single clinical biopsy. The spotting of a panel of peptide aptamers onto a protein microarray matrix could be used to quantify anterior gradient-2 protein from crude clinical biopsy lysates, providing a format for quantitative screening. These data highlight the utility of peptide combinatorial libraries to acquire rapidly a high-affinity ligand that can selectively bind a target protein from a clinical biopsy and provide a technological approach for clinical biomarker assay development in an aptamer microarray format.

Oculo-visual changes and clinical considerations affecting older patients with dementia

Purpose: Dementia is associated with various alterations of the eye and visual function. Over 60% of cases are attributable to Alzheimer's disease, a significant proportion of the remainder to vascular dementia or dementia with Lewy bodies, while frontotemporal dementia, and Parkinson's disease dementia are less common. This review describes the oculo-visual problems of these five dementias and the pathological changes which may explain these symptoms. It further discusses clinical considerations to help the clinician care for older patients affected by dementia. Recent findings: Visual problems in dementia include loss of visual acuity, defects in colour vision and visual masking tests, changes in pupillary response to mydriatics, defects in fixation and smooth and saccadic eye movements, changes in contrast sensitivity function and visual evoked potentials, and disturbance of complex visual functions such as in reading ability, visuospatial function, and the naming and identification of objects. Pathological changes have also been reported affecting the crystalline lens, retina, optic nerve, and visual cortex. Clinically, issues such as cataract surgery, correcting the refractive error, quality of life, falls, visual impairment and eye care for dementia have been addressed. Summary: Many visual changes occur across dementias, are controversial, often based on limited patient numbers, and no single feature can be regarded as diagnostic of any specific dementia. Nevertheless, visual hallucinations may be more characteristic of dementia with Lewy bodies and Parkinson's disease dementia than Alzheimer's disease or frontotemporal dementia. Differences in saccadic eye movement dysfunction may also help to distinguish Alzheimer's disease from frontotemporal dementia and Parkinson's disease dementia from dementia with Lewy bodies. Eye care professionals need to keep informed of the growing literature in vision/dementia, be attentive to signs and symptoms suggestive of cognitive impairment, and be able to adapt their practice and clinical interventions to best serve patients with dementia.

Myopic foveoschisis:a clinical review

To review the literature on epidemiology, clinical features, diagnostic imaging, natural history, management, therapeutic approaches, and prognosis of myopic foveoschisis. A systematic Pubmed search was conducted using search terms: myopia, myopic, staphyloma, foveoschisis, and myopic foveoschisis. The evidence base for each section was organised and reviewed. Where possible an authors' interpretation or conclusion is provided for each section. The term myopic foveoschisis was first coined in 1999. It is associated with posterior staphyloma in high myopia, and is often asymptomatic initially but progresses slowly, leading to loss of central vision from foveal detachment or macular hole formation. Optical coherence tomography is used to diagnose the splitting of the neural retina into a thicker inner layer and a thinner outer layer, but compound variants of the splits have been identified. Vitrectomy with an internal limiting membrane peel and gas tamponade is the preferred approach for eyes with vision decline. There has been a surge of new information on myopic foveoschisis. Advances in optical coherence tomography will continually improve our understanding of the pathogenesis of retinal splitting, and the mechanisms that lead to macular damage and visual loss. Currently, there is a good level of consensus that surgical intervention should be considered when there is progressive visual decline from myopic foveoschisis.

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.

Clinical characteristics of patients with epilepsy in a specialist neuropsychiatry service

Neuropsychiatry services provide specialist input into the assessment and management of behavioral symptoms associated with a range of neurological conditions, including epilepsy. Despite the centrality of epilepsy to neuropsychiatry and the recent expansion of neuropsychiatry service provision, little is known about the clinical characteristics of patients with epilepsy who are routinely seen by a specialist neuropsychiatry service. This retrospective study filled this gap by retrospectively evaluating a naturalistic series of 60 consecutive patients with epilepsy referred to and assessed within a neuropsychiatry setting. Fifty-two patients (86.7%) had active epilepsy and were under the ongoing care of the referring neurologist for seizure management. The majority of patients (N = 42; 70.0%) had a diagnosis of localization-related epilepsy, with temporal lobe epilepsy as the most common epilepsy type (N = 37; 61.7%). Following clinical assessment, 39 patients (65.0%) fulfilled formal diagnostic criteria for at least one psychiatric disorder; nonepileptic attack disorder (N = 37; 61.7%), major depression (N = 23; 38.3%), and generalized anxiety disorder (N = 16; 26.7%) were the most commonly diagnosed comorbidities. The clinical characteristics of patients seen in specialist neuropsychiatry settings are in line with the results from previous studies in neurology clinics in terms of both epilepsy and psychiatric comorbidity. Our findings confirm the need for the development and implementation of structured care pathways for the neuropsychiatric aspects of epilepsy, with focus on comorbid nonepileptic attacks and affective and anxiety symptoms. This is of particular importance in consideration of the impact of behavioral symptoms on patients' health-related quality of life.