The assessment of oral cytology utilizing ploidy analysis and virtual microscopy for the early detection of epithelial dysplasia and neoplasia in oral mucosal lesions

Oral squamous cell carcinoma (OSCC) is associated with high morbidity and mortality which is due, at least in part, to late detection. Precancerous and cancerous oral lesions may mimic any number of benign oral lesions, and as such may be left without investigation and treatment until they are well advanced. Over the past several years there has been renewed interest in oral cytology as an adjuvant clinical tool in the investigation of oral mucosal lesions. The purpose of the present study was to compare the usefulness of ploidy analysis after Feulgen stained cytological thin-prep specimens with traditional incisional biopsy and routine histopathological examination for the assessment of the pre-malignant potential of oral mucosal lesions. An analysis of the cytological specimens was undertaken with virtual microscopy which allowed for rapid and thorough analysis of the complete cytological specimen. 100 healthy individuals between 30 and 70 years of age, who were non-smokers, non-drinkers and not taking any medication, had cytological specimens collected from both the buccal mucosa and lateral margin of tongue to establish normal cytology parameters within a control population. Patients with a presumptive clinical diagnosis of lichen planus, leukoplakia or OSCC had lesional cytological samples taken prior to their diagnostic biopsy. Standardised thin preparations were prepared and each specimen stained by both Feuglen and Papanicolau methods. High speed scanning of the complete slide at 40X magnification was undertaken using the Aperio Scanscope TM and the green channel of the resultant image was analysed after threshold segmentation to isolate only nuclei and the integrated optical density of each nucleus taken as a gross measure of the DNA content (ploidy). Preliminary results reveal that ploidy assessment of oral cytology holds great promise as an adjunctive prognostic factor in the analysis of the malignant potential of oral mucosal lesions.

Quantitative assessment of aortic sclerosis using ultrasonic backscatter

Background. The development of therapeutic interventions to prevent progressive valve damage is more likely to limit the progression of structural damage to the aortic valve with normal function (aortic sclerosis [ASC]) than clinically apparent aortic stenosis. Currently, the ability to appreciate the progression of ASC is compromised by the subjective and qualitative evaluation of sclerosis severity. Methods: We sought to reveal whether the intensity of ultrasonic backscatter could be used to quantify sclerosis severity in 26 patients with ASC and 23 healthy young adults. images of the aortic valve were obtained in the parasternal long-axis view and saved in raw data format. Six square-shaped 11 X 11 pixel regions of interest were placed on the anterior and posterior leaflets, and calibrated backscatter values were obtained by subtracting the regions of interest in the blood pool from the averaged backscatter values obtained from the leaflets. Results. Mean ultrasonic backscatter values for sclerotic valves exceeded the results in normal valve tissue (16.3 +/- 4.4 dB vs 9.8 +/- 3.3 dB, P < .0001). Backscatter values were greater (22.0 +/- 3.5 dB) in a group of 6 patients with aortic stenosis. Within the sclerosis group, the magnitude of backscatter was directly correlated (P < .05) with a subjective sclerosis score, and with transvalvular pressure gradient. mean reproducibility was 2.4 +/- 1.8 dB (SD) between observers, and 2.3 +/- 1.7 dB (SD) between examinations. Conclusion: Measurement of backscatter from the valve leaflets of patients with ASC may be a feasible means of following the progression and treatment response of aortic sclerosis.

Perceptual and instrumental evaluation of voice and tongue function after carotid endarterectomy

Objective: Laryngeal and tongue function was assessed in 28 patients to evaluate the presence, nature, and resolution of superior recurrent laryngeal and hypoglossal nerve damage resulting from standard open primary carotid endarterectomy (CEA). Methods. The laryngeal and tongue function in 28 patients who underwent CEA were examined prospectively with various physiologic (Aerophone II, laryngograph, tongue transducer), acoustic (Multi-Dimensional Voice Program), and perceptual speech assessments. Measures were obtained from all participants preoperatively, and at 2 weeks and at 3 months postoperatively. Results. The perceptual speech assessment indicated that the vocal quality of roughness was significantly more apparent at the 2-week postoperative assessment than preoperatively. However, by the 3-month postoperative assessment these values had returned to near preoperative levels, with no significant difference detected between preoperative and 3-month postoperative levels or between 2-week and 3-month postoperative levels. Both the instrumental assessments of laryngeal function and the acoustic assessment of vocal quality failed to identify any significant difference on any measure across the three assessment periods. Similarly, no significant impairment in tongue strength, endurance, or rate of repetitive tongue movements was detected at instrumental assessment of tongue function. Conclusions: No permanent changes to vocal or tongue function occurred in this group of participants after primary CEA. The lack of any significant long-term laryngeal or tongue dysfunction in this group suggests that the standard open CEA procedure is not associated with high rates of superior recurrent and hypoglossal nerve dysfunction, as previously believed.

Impact of gender on risk stratification by exercise and dobutamine stress echocardiography: long-term mortality in 4234 women and 6898 men

Aims Prior research is limited with regard to the diagnostic and prognostic accuracy of commonplace cardiac imaging modalities in women. The aim of this study was to examine 5-year mortality in 4234 women and 6898 men undergoing exercise or dobutamine stress echocardiography at three hospitals. Methods and results Univariable and multivariable Cox proportional hazards models were used to estimate time to cardiac death in this multi-centre, observational registry. Of the 11 132 patients, women had a greater frequency of cardiac risk factors (P < 0.0001). However, men more often had a history of coronary disease including a greater frequency of echocardiographic wall motion abnormalities (P < 0.0001). During 5 years of follow-up, 103 women and 226 men died from ischaernic heart disease (P < 0.0001). Echocardiographic estimates of left ventricular function (P < 0.0001) and the extent of ischaernic watt motion abnormalities (P < 0.0001) were highly predictive of cardiac death. Risk-adjusted 5-year survival was 99.4, 97.6, and 95% for exercising women with no, single, and multi-vessel ischaemia (P < 0.0001). For women undergoing dobutamine stress, 5-year survival was 95, 89, and 86.6% for those with 0, 1, and 2-3 vessel ischaemia (P < 0.0001). Exercising men had a 2.0-fold higher risk at every level of worsening ischaemia (P < 0.0001). Significantly worsening cardiac survival was noted for the 1568 men undergoing dobutamine stress echocardiography (P < 0.0001); no ischaemia was associated with 92% 5-year survival as compared with death rates of &GE; 16% for men with ischaemia on dobutamine stress echocardiography (P < 0.0001). Conclusion Echocardiographic measures of inducible wall motion abnormalities and global and regional left ventricutar function are highly predictive of long-term outcome for women and men alike.

Who's really hypertensive? - Quality control issues in the assessment of blood pressure for randomized trials

The characterization of blood pressure in treatment trials assessing the benefits of blood pressure lowering regimens is a critical factor for the appropriate interpretation of study results. With numerous operators involved in the measurement of blood pressure in many thousands of patients being screened for entry into clinical trials, it is essential that operators follow pre-defined measurement protocols involving multiple measurements and standardized techniques. Blood pressure measurement protocols have been developed by international societies and emphasize the importance of appropriate choice of cuff size, identification of Korotkoff sounds, and digit preference. Training of operators and auditing of blood pressure measurement may assist in reducing the operator-related errors in measurement. This paper describes the quality control activities adopted for the screening stage of the 2nd Australian National Blood Pressure Study (ANBP2). ANBP2 is cardiovascular outcome trial of the treatment of hypertension in the elderly that was conducted entirely in general practices in Australia. A total of 54 288 subjects were screened; 3688 previously untreated subjects were identified as having blood pressure >140/90 mmHg at the initial screening visit, 898 (24%) were not eligible for study entry after two further visits due to the elevated reading not being sustained. For both systolic and diastolic blood pressure recording, observed digit preference fell within 7 percentage points of the expected frequency. Protocol adherence, in terms of the required minimum blood pressure difference between the last two successive recordings, was 99.8%. These data suggest that adherence to blood pressure recording protocols and elimination of digit preferences can be achieved through appropriate training programs and quality control activities in large multi-centre community-based trials in general practice. Repeated blood pressure measurement prior to initial diagnosis and study entry is essential to appropriately characterize hypertension in these elderly patients.

Myocardial and vascular dysfunction and exercise capacity in the metabolic syndrome

The metabolic syndrome (MS) is associated with cardiovascular risk exceeding that expected from atherosclerotic risk factors, but the mechanism of this association is unclear. We sought to determine the effects of the MS on myocardial and vascular function and cardiorespiratory fitness in 393 subjects with significant risk factors but no cardiovascular disease and negative stress echocardiographic findings. Myocardial function was assessed by global strain rate, strain, and regional systolic velocity (s(m)) and diastolic velocity (e(m)) using tissue Doppler imaging. Arterial compliance was assessed using the pulse pressure method, involving simultaneous radial applanation tonometry and echocardiographic measurement of stroke volume. Exercise capacity was measured by expired gas analysis. Significant and incremental variations in left ventricular systolic (s(m), global strain, and strain rate) and diastolic (e(m)) function were found according to the number of components of MS (p <0.001). MS contributed to reduced systolic and diastolic function even in those without left ventricular hypertrophy (p <0.01). A similar dose-response association was present between the number of components of the MS and exercise capacity (p <0.001) and arterial compliance. The global strain rate and em were independent predictors of exercise capacity. In conclusion, subclinical left ventricular dysfunction corresponded to the degree of metabolic burden, and these myocardial changes were associated with reduced cardiorespiratory fitness.' Subjects with MS who also have subclinical myocardial abnormalities and reduced cardiorespiratory fitness may have a higher risk of cardiovascular disease events and heart failure. (C) 2005 Elsevier Inc. All rights reserved.

Heterozygote effects in mice with partial truncations in the growth hormone receptor cytoplasmic domain: Assessment of growth parameters and phenotype

The GH receptor (GHR) is essential for normal postnatal growth and development, and the molecular basis of GHR action has been studied intensively. Clinical case studies and more recently mouse models have revealed the extensive phenotype of impaired GH action. We recently reported two new mouse models, possessing cytoplasmic truncations at position 569 (plus Y539/545-F) and 391, which were created to identify functional subdomains within the cytoplasmic signaling domain. In the homozygous state, these animals show progressively impaired postnatal growth coupled with complex changes in gene expression. We describe here an extended phenotype analysis encompassing the heterozygote state to identify whether single copies of these mutant receptors bring about partial or dominant-negative phenotypes. It appears that the retention of the ubiquitin-dependent endocytosis motif the N-terminal cytoplasmic domain permits turnover of these mutant receptors because no dominant-negative phenotype is seen. Nonetheless, we do observe partial impairment of postnatal growth in heterozygotes supporting limited haploinsufficiency. Reproductive function is impaired in these models in a progressive manner, in parallel with loss of signal transducer and activator of transcription-5 activation ability. In summary, we describe a more comprehensive phenotypic analysis of these mouse models, encompassing overall and longitudinal body growth, reproductive function, and hormonal status in both the heterozygote and homozygote state. Our results suggest that patients expressing single copies of similarly mutated GHRs would not display an obvious clinical phenotype.

Further evaluation of an EMG technique for assessment of the deep cervical flexor muscles

A novel surface electromyographic (EMG) technique was recently described for the detection of deep cervical flexor muscle activity. Further investigation of this technique is warranted to ensure EMG activity from neighbouring muscles is not markedly influencing the signals recorded. This study compared deep cervical flexor (DCF) muscle activity with the activity of surrounding neck and jaw muscles during various anatomical movements of the neck and jaw in 10 volunteer subjects. DCF EMG activity was recorded with custom electrodes inserted via the nose and fixed by suction to the posterior mucosa of the oropharynx. Surface electrodes were placed over the sternocleidomastoid, anterior scalene, masseter and suprahyoid muscles. Positioned in supine, subjects performed isometric cranio-cervical flexion, cervical flexion, right and left cervical rotation,jaw clench and resisted jaw opening. Across all movements examined, EMG amplitude of the DCF muscles was greatest during neck movements that would require activity of the DCF muscles, particularly during cranio-cervical flexion, their primary anatomical action. The actions of jaw clench and resisted jaw opening demonstrated significantly less DCF EMG activity than the cranio-cervical flexion action (p < 0.05). Across all other movements, the neighbouring neck and jaw muscles demonstrated greatest EMG amplitude during their respective primary anatomical actions, which occurred in the absence of increased EMG amplitude recorded from the DCF muscles. The finding of substantial EMG activity of the DCF muscles only during neck actions that would require their activity, particularly cranio-cervical flexion, and not during actions involving the jaw, provide further assurance that the majority of myoelectric signals detected from the nasopharyngeal electrode are from the DCF muscles. (C) 2005 Elsevier Ltd. All rights reserved.

Psychometric assessment of recovery from mild traumatic brain injury

The Rapid Screen of Concussion (RSC) is a brief psychometric test battery, designed to provide a functional criterion to aid clinical diagnosis of mild traumatic brain injury (mTBI). The present research aimed to examine the utility of this instrument for assessing recovery after mTBI. Three studies were conducted. In Study 1, Discriminant Function Analysis was performed to determine how well the RSC differentiated uninjured controls (N¼16), from mTBI patients (N¼22) and moderate to severe TBI patients (N¼14), several months post-injury. As predicted, moderate to severe TBI patients achieved lower scores than the mTBI and control groups. The RSC also successfully differentiated between each of the diagnostic groups, yielding an overall correct classification rate of 75%. Study 2 examined the predictive utility of the RSC in the mTBI sample (N¼22). Acute injury performance on the RSC was correlated with post-injury scores at an average of 5.5 months post-injury. Statistically significant partial correlation coefficients (r¼0.53r¼0.80) were found for each of the subtests, showing that low acute RSC scores were predictive of poor recovery scores on the RSC after mTBI. In the third study, Reliable Change Indices were calculated on the RSC subtests to examine individual patterns of recovery from mTBI. While 17 of the 23 participants made a significant improvement on their acute injury DSST scores (74%), only 13 of 25 made a significant improvement on the Rapid Sentence Judgement Test (52%), highlighting differential recovery of function, and challenging the notion of full recovery from mTBI within 3 months. These overall results offer support for the construct and predictive validity of the RSC and demonstrate that inexpensive tests of brain function may be useful for managing mTBI acutely for prognosis.

Validation of a generalized transfer function to noninvasively derive central blood pressure during exercise

Exercise brachial blood pressure ( BP) predicts mortality, but because of wave reflection, central ( ascending aortic) pressure differs from brachial pressure. Exercise central BP may be clinically important, and a noninvasive means to derive it would be useful. The purpose of this study was to test the validity of a noninvasive technique to derive exercise central BP. Ascending aortic pressure waveforms were recorded using a micromanometer-tipped 6F Millar catheter in 30 patients (56 +/- 9 years; 21 men) undergoing diagnostic coronary angiography. Simultaneous recordings of the derived central pressure waveform were acquired using servocontrolled radial tonometry at rest and during supine cycling. Pulse wave analysis of the direct and derived pressure signals was performed offline (SphygmoCor 7.01). From rest to exercise, mean arterial pressure and heart rate were increased by 20 +/- 10 mm Hg and 15 +/- 7 bpm, respectively, and central systolic BP ranged from 77 to 229 mm Hg. There was good agreement and high correlation between invasive and noninvasive techniques with a mean difference (+/- SD) for central systolic BP of -1.3 +/- 3.2 mm Hg at rest and -4.7 +/- 3.3 mm Hg at peak exercise ( for both r=0.995; P < 0.001). Conversely, systolic BP was significantly higher peripherally than centrally at rest (155 +/- 33 versus 138 +/- 32mm Hg; mean difference, -16.3 +/- 9.4mm Hg) and during exercise (180 +/- 34 versus 164 +/- 33 mm Hg; mean difference, -15.5 +/- 10.4 mm Hg; for both P < 0.001). True myocardial afterload is not reliably estimated by peripheral systolic BP. Radial tonometry and pulse wave analysis is an accurate technique for the noninvasive determination of central BP at rest and during exercise.

A prospective assessment of SRS-24 scores after endoscopic anterior instrumentation for scoliosis

Study Design. Prospective clinical case series. Objective. To evaluate the clinical outcome of anterior endoscopic instrumention for scoliosis using the SRS-24 questionnaire and to examine how these scores change over a 2-year follow-up period. Summary of Background Data. Anterior endoscopic instrumentation correction has several advantages compared with open procedures. However, the clinical results of this technique using a validated outcome measure have rarely been reported in the literature. Methods. A total of 83 consecutive patients underwent endoscopic anterior instrumentation performed at a single unit. Patients completed the SRS-24 questionnaire before surgery and at 3, 6, 12, and 24 months after surgery. The SRS-24 scores were compared between each of the follow-up intervals. Results. The pain, general self-image, and function from back condition domains improved after surgery (P < 0.05). Activity level significantly improved between 3 and 6 months, and both function domains improved between 6 and 12 months (P < 0.05). None of the domains increased significantly after 1 year. Conclusions. Endoscopic anterior instrumentation for scoliosis significantly improved pain, self-image, and function. The greatest improvement in function occurred between 6 and 12 months after surgery. The SRS-24 scores at 1 year from surgery may provide a good indicator of patient outcome in the long-term.

A pilot study of online assessment of childhood speech disorders

We investigated the feasibility of assessing childhood speech disorders via an Internet-based telehealth system (eREHAB). The equipment provided videoconferencing through a 128 kbit/s Internet link, and enabled the transfer of pre-recorded video and audio data from the participant to the online clinician. Six children (mean age = 5.3 years) with a speech disorder were studied. Assessments of single-word articulation, intelligibility in conversation, and oro-motor structure and function were conducted for each participant, with simultaneous scoring by a face to face and an online clinician. There were high levels of agreement between the two scoring environments for single-word articulation (92%), speech intelligibility (100%) and oro-motor tasks (91%). High levels of inter- and intra-rater agreement were achieved for the online ratings for most measures. The results suggest that an Internet-based assessment protocol has potential for assessing paediatric speech disorders.

Motion analysis of right ventricular wall based on an electromechanical biventricular model

Based on our previously developed electrical heart model, an electromechanical biventricular model, which couples the electrical property and mechanical property of the heart, was constructed and the right ventricular wall motion and deformation was simulated using this model. The model was developed on the basis of composite material theory and finite element method. The excitation propagation was simulated by electrical heart model, and the resultant active forces were used to study the ventricular wall motion during systole. The simulation results show that: (1) The right ventricular free wall moves towards the septum, and at the same time, the base and middle of free wall move towards the apex, which reduce the volume of right ventricle; (2) The minimum principle strain (E3) is largest at the apex, then at the middle of free wall, and its direction is in the approximate direction of epicardial muscle fibers. These results are in good accordance with solutions obtained from MR tagging images. It suggests that such electromechanical biventricular model can be used to assess the mechanical function of two ventricles.