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Biomedical subjects

B Ross

Publications and source records attributed to B Ross.

At least 37 records · Page 2Linked to original sources

Chemical and biochemical microsensors in silicon for the clinical on-line monitoring.

Miniaturised chemosensors and biosensors for applications in clinical diagnostics and biomedical fields can be fabricated in silicon with high reproducibility using the containment technology. They are characterised by excellent durability of the sensitive membranes. Meanwhile, there are sensors available for a variety of relevant medically parameters such as pH, the blood electrolytes sodium, calcium, potassium, and the blood metabolites glucose and lactate. The miniaturised sensors provide the opportunity to develop product solutions with minimal sampling volume requirements for the "Point of Care (POC)" sector through the combination of innovative microtechnical components. Two examples are presented, such microsystems have been implemented for the medical applications of "Blood Monitoring" and "Glucose Monitoring".

Blood Chemical Analysis↗

Electro-magnetic base technology for estremely sensitive immunosensors and DNA-chips.

We report on the development of an innovative electro-magnetic base technology for estremely sensitive sensors allowing the electrical detection of biological analytes like antigenes or DNA as well as a simple multiple detection of binding forces occurring at specific bonds between proteins. The technology is based on the strong impact of specifically captured magnetic microbeads on an electrical current generated in a fluid by a small sensor chip with an array of activated microelectrodes. The new technological principle with the on-chip detection of analytes will be suitable for large scale applications due to its mass production compatible technologies and allow an alternative way to monitor relevant substances without the consumption of critical additional solutions and reagents.

Biosensing Techniques↗

[AIDS and non-Hodgkin's lymphoma: initial cardiac manifestations of highly malignant B-cell lymphoma 18 years after HIV infection].

HISTORY AND FINDINGS: A 35-year-old man who, as a result of intravenous drug abuse, had become infected with HIV 18 years previously, was admitted with signs of right-heart failure. Three months earlier a systolic murmur had first been heard in the 5th intercostal space parasternally. INVESTIGATIONS: Transesophageal echocardiography (TEE) demonstrated a 3 x 2 cm right atrial tumour, moderate to severe tricuspid regurgitation and pulmonary hypertension. Blood cultures grew Streptococcus. DIAGNOSIS, TREATMENT AND COURSE: Endocarditis with atrial thrombi and recurrent pulmonary emboli was diagnosed and treated with antibiotics and anticoagulants. Three weeks later the TEE showed an increase in the atrial tumour. Computed tomography of skull, thorax and abdomen did not demonstrate any significantly enlarged lymph nodes. Exploratory thoracotomy revealed an infiltrating highly malignant centroblastic non-Hodgkin's lymphoma (NHL) of almost the entire free wall of the right atrium. After two courses of chemotherapy (CHOP protocol) the size of the tumour had significantly decreased. CONCLUSION: The differential diagnosis of a right atrial tumour can be difficult in patients with HIV or AIDS. Even if the site is atypical and there is no lymphadenopathy, a lymphoma should be considered. In case of doubt a histological diagnosis via an exploratory thoracotomy should be performed.

Adult↗

Timbre-specific enhancement of auditory cortical representations in musicians.

Neural imaging studies have shown that the brains of skilled musicians respond differently to musical stimuli than do the brains of non-musicians, particularly for musicians who commenced practice at an early age. Whether brain attributes related to musical skill are attributable to musical practice or are hereditary traits that influence the decision to train musically is a subject of controversy, owing to its pedagogic implications. Here we report that auditory cortical representations measured neuromagnetically for tones of different timbre (violin and trumpet) are enhanced compared to sine tones in violinists and trumpeters, preferentially for timbres of the instrument of training. Timbre specificity is predicted by a principle of use-dependent plasticity and imposes new requirements on nativistic accounts of brain attributes associated with musical skill.

Acoustic Stimulation↗

Magnetic resonance spectroscopy of the human brain.

Magnetic resonance (MR; synonymous with NMR = nuclear magnetic resonance) is a universal physical technique best known for non-invasive detection and anatomical mapping of water protons (H). MR-spectroscopy (MRS) records protons from tissue chemicals other than water, intrinsic phosphorus containing metabolites, sodium, potassium, carbon, nitrogen, and fluorine. MRS is therefore an imaging technique with the potential to record human and animal biochemistry in vivo. As a result of wide availability of MRI equipment in research laboratories and hospitals, MRS is a serious competitor with PET to define normal body composition and its perturbation by pharmacological and pathological events. This article describes practical aspects of in vivo MRS with particular emphasis on the brain, where novel metabolites have been described. A survey of these new aspects of neurochemistry emphasize their practical utility as neuronal and axonal markers, measures of energy status, membrane constituents, and osmolytes, as well as some xenobiotics, such as alcohol. The concept of multinuclear in vivo MRS is illustrated by diagnosis and therapeutic monitoring of several human brain disorders. Although these methods are currently most frequently encountered in human studies, as well as with transgenic and knockout mouse models, MRS adds a new dimension to anatomic and histopathologic descriptions.

Brain↗

Human auditory middle latency responses: influence of stimulus type and intensity.

Human auditory middle latency responses (MLR) to click and tone pip stimuli of different intensities were recorded by means of magnetoencephalography (MEG) and electroencephalography (EEG). Clicks elicited larger responses with significantly shorter latencies than the tone pips at the same intensity in dB sensation level (SL). Most MLR amplitudes increased and their latencies decreased with increasing stimulus intensity for both types of stimulation. Pa and Nb amplitudes saturated at intensities of 60 dB SL in the case of click stimulation. The shorter latencies of MLR evoked by the click were explained by its short rise time and the high frequency content of its spectrum. MEG source analysis yielded MLR sources which were clearly different from those of the slow cortical wave N1. They seem to be located in primary auditory areas along Heschl's gyrus.

Acoustic Stimulation↗

Employee response to major organizational redesign.

A number of health care organizations are currently undergoing major organizational redesign. Despite these efforts, little is known about how these changes are affecting the employees participating in the redesign process. In response to this, a study was undertaken to determine the perceived impact of organizational redesign on nursing staff at 2 acute care hospitals that were undergoing major organizational change. Data were collected through semi-structured focus group interviews conducted on all 3 shifts (days, evenings, and nights). Findings suggest the early redesign period is highly turbulent and difficult for staff. Nurses expressed concern over changes in roles and responsibilities, disruption in work group relationships, loss of resource availability, reduction in quality of care, and alterations in physical and psychological state.

Attitude of Health Personnel↗

Pharmacokinetics and pharmacodynamics of sotalol in a pediatric population with supraventricular and ventricular tachyarrhythmia.

OBJECTIVE: This pharmacokinetic-pharmacodynamic study was designed to define the steady-state relationship between pharmacologic response and dose or concentration of sotalol in children with cardiac arrhythmias, with an emphasis on neonates and infants. METHODS: The treatment consisted of an upward titration with unit doses of 10, 30, and 70 mg of sotalol per square meter of body surface area. The patients received 3 doses at each dose level. The dosing interval was 8 hours. The Class III and beta-blocking activities of sotalol were derived from the QT and R-R intervals, respectively, of the surface electrocardiogram, which was recorded at 6 scheduled times before and after the third, sixth, and ninth doses. During these three dose intervals, 4 scheduled blood samples were also collected. Drug concentrations were measured with a validated nonstereoselective liquid chromatographic tandem mass spectrometric detection assay. Pharmacokinetic and pharmacodynamic parameters were obtained with standard methods. RESULTS: Twenty-one centers enrolled 25 patients in the study: 7 were neonates, 9 were infants, and 11 were children between the ages of 2 years and 12 years. The area under the drug concentration-time curve increased proportionately with dose. The apparent oral clearance of sotalol was linearly correlated with body surface area and creatinine clearance. The smallest children (body surface area <0.33 m2) displayed greater drug exposure than the larger children. The increase of QTc and R-R intervals was dose dependent. At the 70-mg/m(2) dose level, the mean (+/- standard deviation) maximum increase for the QTc interval was 14% +/- 7% and the average Class III effect during a dose interval was 7% +/- 5%. At the same dose level, the mean maximum increase of the R-R interval was 25% +/- 15% and the average beta-blocking effect during a dose interval was 12% +/- 13%. The effects tended to be larger in the smallest children. The Class III response and the plasma concentrations of sotalol were linearly related. The treatment was well tolerated. CONCLUSIONS: The steady-state pharmacokinetics of sotalol were dose proportionate. Pharmacologically important beta-blocking effects were observed at the 30-mg/m2 and 70-mg/m2 dose levels. Important Class III effects were seen at the 70-mg/m2 dose level. The Class III effect was linearly related to the drug concentration.

Anti-Arrhythmia Agents↗

Metabolism of rabbit angiostatin glycoforms I and II in rabbits: angiostatin-I leaves the intravascular space faster and appears to have greater anti-angiogenic activity than angiostatin-II.

Plasminogen (PLG) exists in the circulation as two glycoforms, I and II. Angiostatin (AST) is a polypeptide that has been cleaved from the kringle region of PLG and has strong anti-angiogenic properties. AST-I and AST-II, which consisted only of kringles 1 through 3, were prepared by the action of urokinase on purified rabbit PLG-I and PLG-II, respectively, in the presence of N-acetyl cysteine, followed by affinity chromatography on lysine-Sepharose. Purified AST-I and AST-II were tested for functional activity with a chick chorioallantoic membrane (CAM) model; when similar amounts were applied to a 6-day CAM, AST-I was substantially more effective than AST-II in decreasing vascular supply to the CAM over a 72-hour period; this activity correlated with a loss of capillaries, probably through apoptosis of endothelial cells. Radiolabeled AST-I and AST-II (iodine 125 and iodine 131) were co-injected intravenously into healthy rabbits to determine their clearances from plasma measured over 3 days. Over a dose range of 0.08 to 2.7 microg/kg, the fractional catabolic rate within the intravascular space (j(3)) indicated that AST-I was cleared 3-fold to 4-fold more rapidly than AST-II (P < .001). The catabolic half-life of AST-I (2.01 +/- 0.19 days) was significantly less than that of AST-II (2.62 +/- 0.20 days). The faster clearance of AST-I from the intravascular space was matched by its more rapid passage than AST-II to the extravascular space of various organs over 60 minutes in vivo. This property of AST-I as compared with AST-II may partially explain its greater anti-angiogenic potential. From the plasma concentrations of PLG-I and PLG-II and their relative behaviors toward rabbit VX-2 lung tumors in vivo, we predict that substantially greater quantities of AST-II than AST-I may be released into the extravascular space of tumors.

Angiostatins↗

Metabolism of rabbit plasma-derived factor VII in relation to prothrombin in rabbits.

In the human circulation, factor VII is present in relatively low plasma concentration (0.01 microM) and has been reported to have a short half-life (t(1/2); 6 h). In contrast, prothrombin is present in a relatively high plasma concentration (2 microM) and has a relatively long catabolic half-life (t(1/2) = approximately 2-3 days). This report examines the metabolic characteristics of purified rabbit plasma factor VII and prothrombin, radiolabeled with (125)I and (131)I, respectively, in healthy young rabbits. From the plasma clearance curves of protein-bound radioactivities, fractional catabolic rates and compartmental distributions were calculated using a three-compartment model. Turnover of factor VII within the intravascular space (2.95 days) exceeded that of prothrombin (1.9 days). However, the whole body fractional catabolic rate of factor VII (0.34 days(-1); catabolic t(1/2) = 2.04 days) was significantly slower than that of prothrombin (0.53 days(-1); t(1/2) = 1.31 days). Furthermore, the fractional distributions of factor VII in the intravascular (0.14) and extravascular compartments (0.76) differed from those of prothrombin (0.29 and 0.53). Absolute quantities of factor VII and prothrombin catabolized by a 3-kg rabbit amounted to 0.18 and 24.0 mg/day, respectively (molar ratio of prothrombin to factor VII = 100). The molar ratio of catabolism was compared with the release rates of factor VII and prothrombin from rabbit livers perfused ex vivo. After correction for uptake of factor VII and prothrombin by the liver, the molar ratio of released prothrombin to factor VII in the perfusate was approximately 293:1 over a 0.25- to 3-h interval. These results indicate that, compared with prothrombin, factor VII in the healthy rabbit circulates as a relatively long-lived protein. This behavior does not reflect that reported for factor VII in the human circulation.

Animals↗

Functional assessment of older adults in an emergency department.

The fast paced nature of emergency medicine often precludes assessment of patient functioning which may have significant consequences for geriatric patients including falls, functional decline and/or hospital re-admission. A rehabilitation consultation service to a hospital emergency department was implemented based on recommendations in the literature that functional assessments and a multidisciplinary approach be used with older adults. A systematic method of targeting and assessing elderly at-risk patients included a safety checklist and a comprehensive functional assessment tool. An observational study of 80 patients receiving functional assessments from rehabilitation professionals is described. Patients with high levels of disability or who lived alone prior to the emergency visit were more likely to be admitted to hospital. This study supports using multidisciplinary efforts and comprehensive functional assessments in emergency departments to guide decision-making about discharge outcome and planning for the health care needs of elderly patients.

Aged↗

Reliability of the Sunnybrook Facial Grading System by novice users.

OBJECTIVES: To evaluate the intrarater and inter-rater reliability of the Sunnybrook Facial Grading System (SFGS) by novice users. DESIGN: Prospective interval study using one measurement instrument. SETTING: Tertiary teaching hospital (Sunnybrook & Women's College Health Science Centre). METHODS: Twenty-two patients with a wide spectrum of facial dysfunction recorded on videotapes were rated using the SFGS by eight novice observers independently in two different sittings separated by 3 weeks. The order of patients was randomized for the second sitting. Intraclass correlation coefficients were calculated for component scores and for total scores within and between raters. RESULTS: The intrarater reliability coefficients for the eight raters ranged from .838 to .929. This largely overlaps with the data obtained in previous studies with expert raters. The inter-rater reliability for all eight raters at time 1 was .982 and for time 2 was .970. This is higher than what was previously obtained with expert raters. CONCLUSION: The SFGS is as reliable when applied by novice users as by expert users.

Facial Nerve Diseases↗

Brain stem auditory evoked fields in response to clicks.

Magnetoencephalographic correlates of brain stem auditory evoked potentials (BAEP) have been identified by applying the model of a current dipole with invariant location and orientation (fixed dipole) to data recorded with a 37-channel first-order gradiometer system. In all three subjects studied, the dominating wave of the recorded brain stem auditory evoked field (BAEF) coincided exactly with wave V in the contralateral BAEP (maximal field amplitude of the order of 2-3 fT). In one subject, also a wave preceding wave V was observed, which was associated with basically the same spatial pattern as wave V itself, but had an opposite polarity. The study suggests that the supplementary information provided by BAEF measurements could be decisive for a better understanding of human auditory evoked brain stem activity.

Acoustic Stimulation↗

A combined functional in vivo measure for primary and secondary auditory cortices.

Auditory evoked magnetic fields are reliable physiological in vivo markers of activity generated in auditory cortices. In recent years, several components of auditory evoked fields have been demonstrated with specific topographies within the auditory cortex in man. Their differential elicitation and analyses has rendered the discrimination of neural activities in primary vs. secondary auditory cortical fields possible. This in vivo measure may be of interest in a number of (neuro)psychiatric and neuropsychological disorders with central auditory deficits, in which in vivo anatomical measures do not allow a clear distinction of primary vs. secondary auditory cortex involvement. To help better understand the pathophysiology of such disorders, we developed and introduce a combined measure of steady-state field (SSR) and the N1 component of the transient evoked field. The acoustic stimulus for this paradigm consists of a 500-ms tone burst with 39-Hz amplitude modulation of the carrier frequency. This combined stimulation allows assessment of both auditory cortex components in one brief examination to be well tolerated by patients. We examined the source locations of SSR and N1 component with separate classical stimulation and combined stimulation within-session in healthy volunteer subjects. We demonstrate here that the distinct sources of steady-state (primary auditory cortex) and N1 (secondary auditory cortex) responses can be reliably measured without significant spatial distortion with this combined stimulation paradigm.

Acoustic Stimulation↗

Positional cloning and characterisation of the human DLGAP2 gene and its exclusion in progressive epilepsy with mental retardation.

In search of the gene for progressive epilepsy with mental retardation (EPMR) we identified DLGAP2, the human homolog of the gene encoding the rat PSD-95/SAP90-associated protein-2 (Dlgap2). We extended the transcript in both the 5' and 3' directions and characterised the genomic structure of the approximately 10 kb gene. Sequence comparisons of human DLGAP2 cDNA sequences obtained from human testis and brain cDNA libraries with homologous rat genes suggest alternative splicing in the 5' end of the gene. The 5' coding sequence of the testis cDNA is complete, whereas based on homology with the rat gene 103 bp of coding sequence may still be missing in the 5' end of the DLGAP2 brain transcript. DLGAP2 was excluded as the gene responsible for EPMR.

Base Sequence↗

Metabolism and distribution of the virus-encoded serine proteinase inhibitor SERP-1 in healthy rabbits.

SERP-1 is a secreted myxoma virus-encoded 55-kd protein of the serine proteinase inhibitor ("serpin") family that strongly inhibits the mitosis of medial arterial smooth muscle cells, thus preventing stenosis in injured rabbit and rat arteries. We have measured the fractional catabolic rate (FCR) and compartmental distribution of 1251-SERP-1 after injection of various doses into the circulation of healthy rabbits. The FCR within the intravascular space decreased from 2.99 d(-1) to 2.39 d(-1) and the whole-body FCR decreased from 0.66 d(-1) to 0.51 d(-1) as the dose was increased 35-fold from 0.11 microg/kg to 3.8 microg/kg. The fractional distribution of SERP-1 between the intravascular (0.21), noncirculating vascular wall (0.09), and extravascular compartments (0.70) at equilibrium did not change significantly over this dose range. SERP-1 did not appear to selectively accumulate in any organ in any of 11 rabbits studied over a 6-day interval. In comparison to other rabbit plasma serpins, the behavior of SERP-1 in vivo most closely resembled that of heparin cofactor II.

Animals↗

Long term response to gallstone treatment--problems and surprises.

OBJECTIVE: To re-evaluate after 5 years the results of a randomised trial of cholecystectomy and lithotripsy for the treatment of symptomatic gallstones. DESIGN: Late follow-up of a randomised controlled trial. SETTING: Teaching hospital, UK. SUBJECTS: 144 of the 179 patients originally randomised. INTERVENTIONS: Either elective open cholecystectomy under general anaesthesia or a maximum of 4 sessions of lithotripsy (up to 3000 shocks/session) on consecutive days with no anaesthesia or analgesia. RESULTS: Of the original 87 patients randomised to be treated by lithotripsy, 39 (45%) subsequently underwent cholecystectomy, most of them within 32 months of treatment ("crossover" group). Patients in both main groups had a pronounced reduction in the number of episodes of pain at 5 years and significant reductions in the mean severity scores both on VAS and the McGill rating. Those in the crossover group had the worst scores. Gastrointestinal symptoms improved in the two main groups, but again the crossover group did least well. Quality of life improved significantly over baseline in the two main groups, but was much poorer in the crossover group. CONCLUSIONS: Patients who had primary cholecystectomy were more likely to be free of pain than those treated by lithotripsy. Lithotripsy gave good symptomatic results in 55% of patients, and this was not dependent on clearance of stones. Patients who had a cholecystectomy after lithotripsy had the worst symptomatic results. It is difficult to identify patients who will not benefit from lithotripsy, but the presence of many coexisting symptoms may be an important predictor.

Adult↗